Subsections

Food poisoning


Algal Toxins

Algae

Algae may present variable morphology. Species are known being unicellular, other algae may grow up to 20 to 30 meters of length.
Algae serve as food for marine animals, they may be used as ingredients such as the production of agar agar, used in food, in drugs, as basis for bacteriological medias and is used in many other ways. Chlorophyll is often hidden by yellow, brown,blue and red pigments.This gave the origin to a classification of algae in Xantophyceae, Cyanophyceae or Rodophyceae.
Algae produce starch, mannite, leucosine and oil.
Algae are generally inhabitants of water. Algae adapted to life in contact with air are found on the surface of rocks, on the bark of trees and at soil. In extreme cases they may survive at 70$^{o}C$ (Cyanophyceae).
Algae are an important factor of regeneration of water and treatment of drinking water. Microscopical identification of algae is used in the characterisation of quality of water.
Algae are important part of marine plankton serving as food for a variety of aquatic animals. Chlorella pyrenoidosa, unicellular alga was studied as a possible food. Rodoficeae are industrially used to obtain natural carotene. In reduce amount dehydrated algae are used as food in Japan.


Classification of alga

[128] Classifications are often not up to date but some are didactical and will still be used even when there is a new classification proposed so this is why the present classification proposed by Strasburger is used here: The plant kingdom is divided in 7 great divisions :
  1. Bacteriophyta containing bacteria
  2. Cyanophyta containing the blue-green Alga
  3. Phycophyta containing all other alga
  4. Mycophyta containing mushrooms
  5. Bryophyta containing the mosses
  6. Pteridophyta containing ferns
  7. Spermatophyta containing plants with seeds
Alga which produce toxins are settled in division 2 Cyanophyta and division 3 Phycophyta.

Division 2: Cianophyta:

The division contains the following orders:

Division 3: Phycophyta:

This division contains algae organised as Flagellatae with the following orders: The Flagellatae have subdivision

Classification of microorganism according Streble

[139]
  1. Phylum Bacteriophyta(Bacteriae) Order Eubacteriales
    Order Actinomycetales
    Order Chlamydobacteriales
  2. Phylum Cyanophyta(Blue algae) Order Chroococcales
    Order Pleurocapsales
    Order Chamaesiphonales
    Order Stigonematales
  3. Order Chrysophyta(Yellow algae) Class Chrysophyceae(Gold algae)
    Order Chrysomonadales
    Order Rhizochrysidales
    Order Chrysocapsales
    Class Bacillariophyceae, Diatomae ( Diatom )
    Order Centrales
    Order Pennales
    Class Xanthophyceae (Yellow-green algae)
    Order Heterogloeales (Heterocapsales)
    Order Heterococcales
    Order Heterosiphonales
  4. Euglenophyta Order Euglenales
    Order Peranematales
  5. Phylum Dinophyta Class Dinophyceae
    Order Peridiniales
  6. Phylum Cryptophyta
  7. Phylum Chlorophyta(Green Algae) Class Chlorophyceae
    Order Volvocales
    Order Tetrasporales
    Order Chlorococcales
    Order Ulotrichales
    Order Ulvales
    Order Prasiolales
    Order Microsporales
    Order Chaetophorales
    Class Oedogoniophyceae
    Class Bryopsidophyceae
    Order Cladophorales
    ivermectin Order Sphaeropleales
    Class Conjugatophyceae
    Order Mesotaeniales
    Order Gonatozygales
    Order Desmidiales
    Order Zygnemales
  8. Phylum Rhodophyta(Red algae) Order Banglales
    Order Nemalionales
    Order Cryptonemiales
  9. Phaeophita(Brown algae) Order Ectocarpales
  10. MycophytaOrder Archimycetes Order Phycomycetes
    Order Ascomycetes
    Order Basidiomycetes
    Order Fungi imperfecti

Algal toxins

Beside useful algae there are many single cell algae which produce toxins. These species develop rapidly under favourable conditions forming algae carpets in seawater killing fish in Mexico gulf and North Sea (such as Microcystis).
Marine animals such as oysters,Crustaceae and different types of fish may eat the toxic algae storing the toxins. This can lead to serious poisoning.
According to the species of algae the symptoms of poisoning are[125]:
  1. Damage of the nervous system (Paralytical Shellfish Poisoning)(PSP)
  2. Loss of memory(Amnesic Shellfish Poisoning)(ASP)
  3. Neurotoxic phenomenons(Neurotoxic Shellfish Poisoning)
  4. Sodium channel blocking in nervous cells(Tetrodotoxin)(TTX)
In the summer the temperature of seawater rises causing high growth of algae. In the Netherlands the harvest of oysters are stopped at this time of the year or the oysters are transfered to unpolluted water tanks to regenerate.

The alga Fibrocapsa japonica was found in the German Bay. This alga produces a toxin which is associated with the death of seals. According to Ursula Siebert from the Forschung und Technologie Zentrum , Büsum, Germany, was found in samples of the German Bay for the first time in 1995. How the toxin of Fibrocapsa japonica acts and if it can harm humans is unknown[800]. In USA and Canada the maximum tolerable value of saxitoxin is 0,8 mg/Kg of mollusc meat. In Germany absence of liposoluble DSP is provided by regulations. Water soluble PSP should not exceed 400 micrograms/Kg of mollusc meat. The maximum tolerable amount of dominoic acid in Germany is 20 mg DA/kg mollusc meat.


Harmful Algal Blooms (HAB):

Harmful Algal Blooms (HAB) is a natural disaster which has attracted global attention in recent decades since it threatens greatly public health, causes economic damage to fisheries and tourism. Fibrocapsa japonica is one of HAB causative organisms which caused significant loss to coastal fisheries in Japan. From the 1990's it was also reported frequently in European coastal waters.

In a work of the University of Oldenburg, the toxicity of Fibrocapsa japonica algal cells was first established by Artemia salina biotest. Fibrocapsins was screened step by step through Artemia salina biotest, bioluminescence inhibition biotest and erythrocyte lysis assay methods, isolated then in HPLC.

The chemical natures of fibrocapsins 1, 2 and 3 were determined finally as 6,9,12,15-octadecatetraenoic acid, all-cis-5,8,11,14,17-eicosapentaenoic acid and all-cis-5,8,11,14-eicosatetraenoic acid by HPLC-MS, IR, GC-(HR)MS, NMR experiments and biotest. The toxins are unsaturated fatty acids. (Isolation and characterisation of toxins from Fibrocapsa japonica (Raphidophyceae) / Meng Fu. - 2003. - V, 85 Bl. - Oldenburg, Univ., Diss., 2003)

Harmful algae blooms buoy: Dr. Phil Culverhouse from the University of Plymouth developed the HAB (harmful algae blooms)-Buoy. This project was funded by the European Union. The buoy is a swimming microscope coupled natural object recognition software. It can image and recognise harmful algae. It will be operated either underwater suspended from a buoy or on a mussel-producing raft, or in the laboratory to monitor algae. The relevant specimens which are scanned from filtered water will be further analysed to decide on their species label. This enables shell fishery staff to have advance warning that HAB species are present. Tests are instruments will be located in Galicia in Spain, Galway in Ireland, and the Gulf of Trieste in Italy.


Damage of the nervous system (Paralytical Shellfish Poisoning)(PSP)

They are caused by toxins produced by Dinoflagelata such as Alexandrium spp. The PSP toxins are water soluble.

Analytical methods

Mouse-Bioassay: A biological test giving immediate informations about the activity of the toxins in whole. To study the different paralytic toxins chromatography methods are necessary, such as the use of the ionicpair chromatography with RP-C18 and a step gradient making possible to separate PRP toxins.


Damage of the digestive tract (Diarrhetic Shellfish Poisoning)(DSP):

Toxins of Diarrhetic Shellfish Poisoning (DSP) are okada acid (okadaic acid) the Dinophysis toxin, the pectenotoxins and yessotoxin which are liposoluble causing strong diarrhoea.

Analytical methods

At the beginning there were only biological tests in rats and mice, the Bioassays and immunological tests, the immunoassays. Modern HPLC methods with derivatization before column with fluorescence marker using a fluorescence detector can detect very small amounts of toxins.
Using HPLC/MS coupling with Atmospheric Pressure/Electrospray Ionisation (API/ESI)-Interfaces better results may be achieved.

DSP: Diarrhoeic Shellfish Poisoning (A colorimetric phosphatase inhibition assay)

[111]
To detect DSP toxins, a colorimetric phosphatase inhibition assay was developed using a highly purified recombinant human PP2A C-subunit, which is produced by a recombinat Baculovirus. The assay is very sensitive, fast, easy,accurate, reproducible and inexpensive to detect DSP toxins (OA group) in the shellfish. The intensity of the color is proportional to the enzyme activity and the absorbance is measured at 405 nm. The lowest detectable concentration of OA is 0.1 $\mu$g/g in shellfish digestive glands,which comprise about 10-30% of all the soft tissue of the shellfish by weight.

The DSP Rapid Kit was developed following the studies of Takai and Mieskes 1991, and Tubaro and colleagues 1996 which proposed the assay as routine assessment of okadaic acid shellfish contamination, stressing that it is sensitive, rapid and does not require expensive equipment. [112] [113]


Loss of memory (Amnesic Shellfish Poisoning)(ASP)

A poisoning with ASP in Canada affecting about 100 persons was related in 1987. These persons had eaten meat of mollusks which were intoxicate with ASP. The survivals had amnesia. This gave the name of the poisoning which is caused by the dominoinic acid of the alga Nitzschia pungens. This alga is found also in Europe turning oysters poisonous. The maximum tolerable amount of dominoic acid in Germany is 20 mg DA /Kg mollusc meat.

Analytical methods

HPLC is used as analytical method of ASP using an RP-C18 column without derivatization. Dominoinic acid down to 1,0 mg/kg mollusc meat can be detected with this method. Making derivatization of dominoinic acid before the column using fluorenilmetoxicarbonylchlorid. Amounts below 1 mg/Kg can be detected.

Neurotoxic phenomenons(Neurotoxic Shellfish Poisoning):

The NSP toxins are produced by Gymnodinium breve, also denominated as Ptychodiscus brevis.
This alga has several times caused death to fish in the Gulf of Mexico.
APS toxins may be classified in to types: Brevetoxin A and Brevetoxin B. They are a group of polyethers.

Analytical methods:

HPLC and immunoassays and HPLC with MS coupling.


Sodium channel blocking in nervous cells (Tetrodotoxin)(TTX)

Tetrodotoxin is also called fugu-toxin. It may be produced by some fish of the family of Tetradontidae (Takifugu sp.). This ball-fish is being consumed in Japan causing sometimes severe poisoning.
The toxin TTX blocks the sodium channel of nervous cells acting neurotoxic.
This toxin has no absorbtion of ultra violet light and is not fluorescent.
HPLC is used with derivatization before column, producing a fluorescent derivate with sodium hydroxide.
The HPLC/MS coupling with an API/ESI interface is used with good results and in some cases chromatography with mass spectrometry recheck.

Saxitoxin:

Saxitoxin is an algal toxin of the PSP type, being water soluble. More 20 derivates of saxitoxin are produced by Dinoflagelata such as Alexandrium spp.

Analytical method to determine Saxitoxin [114]

Summary:Saxitoxin is an algal toxin which is extracted in acid solution.
After extraction the toxin is purified with periodic acid in alkaline medium. Saxitoxin is then read fluorimetricaly against a standard curve.
The food to be analysed is triturated in trichloracid 1 N and hydrochloric acid 0,2N in equal parts.
After 20 minutes heating it is filtered, taken to pH 5.2 +-0.1 with potassium hydroxide 1 mol/l and centrifugated and transfered to a column with ion exchange resin in ME+ form 50 to 100 mesh to purify the saxitoxin.
The column is then washed with 100 ml buffer of potassium acetate at a pH of 5.2+-0.1 followed with 50 ml distilled water.
Saxitoxin is then eluated with sulfuric acid 0,5N until 20 ml are obtained in a volumetric flask.
The velocity of elution should not exceed 3 ml/minute.
2 ml of the elution are mixed with 2 ml NH$_{4}$OH 1,2 N and 100 microliter of periodic acid 0.1 ml/l. After 15 Minutes 200 microliter of glacial acetic acid are added to the solution and read against a blank containing the same components as before having periodic acid changed with water.
Standard solution: Saxitoxin dissolved in acetic acid 0,1 ml/l. Further dilution are made with sulfuric acid in a way that 2 ml of the dilutions are added to 2 ml NH$_{4}$OH 1,2 N and 100 microliter of periodic acid. Reading is made at 388 nm. The blank should be subtracted from the value of the sample. Before using purifying column the resins must be suspended three times in 50 ml chloridric acid 3N and washed with distilled water until reaction is neutral.
Again the resin must be suspended 2 times in 50 ml acetic acid 2mol/l. The upper layer is then exchanged by 150 to 200 ml acetic acid and the pH is adjusted to 5.2+-0.1 with acetic acid. The resin can be kept until use under a buffer solution of potassium acetate 0,2 mol/l at an pH of 5.2+-0.1 adjusted with acetic acid. The column of 1 cm diameter is charged with approximately 5 g resin which gives a length of 5 cm.

Health regulations related to bivalve molluscs and other marine species

[115]
Health concerns related to shellfish, live bivalve molluscs and other aquatic animals contaminated with coli, salmonella or other bacteria or viruses as well as algal toxins are of public concern. Actual global warming may spur micro organisms in water turning and turn it necessary to tighten safety control on molluscs.

The Council Directive 91/492/EEC of 15 July 1991 lays down the health conditions for the production and the placing on the market of live bivalve molluscs. It define production areas from which molluscs can bet gathered for direct human consumption, or from which they have to be purified or relayed.

It is primarily the responsibility of the producers to ensure that the bivalve molluscs are produced and placed on the market in compliance with the health requirements prescribed; whereas the competent authorities must, carry out checks and inspections, to ensure that producers comply with those requirements do not contain microorganisms and toxic substances in quantities which are considered to be dangerous to human health.

Live bivalve molluscs from purification areas must not exceed the limits of a five-tube, three-dilution MPN-test of 6 000 faecal coliforms per 100 g of flesh or 4 600 E. Coli per 100 g of flesh in 90% of samples.

Live bivalve molluscs from areas where they do not exceed the limits of a five-tube, three-dilution MPN-test of 60 000 faecal coliforms per 100 g of flesh.can be collected but placed on the market only after relaying over a long period (at least two months).

Requirements concerning live Bivalve Molluscs intended for immediate consumption

1. The possession of visual characteristics associated with freshness and viability, including shells free of dirt, an adequate response to percussion, and normal amounts of intravalvular liquid.

2. They must contain less than 300 faecal coliforms or less than 230 E. Coli per 100 g of mollusc flesh and intravalvular liquid based on a five-tube, three-dilution MPN-test or any other bacteriological procedure shown to be of equivalent accuracy.

3. They must not contain salmonella in 25 g of mollusc flesh.

4. They must not contain toxic or objectionable compounds occurring naturally or added to the environment such as those listed in the Annex to Directive 79/923/EEC. [116]

5. The upper limits as regards the radionuclide contents must not exceed the limits for foodstuffs as laid down by the Community.

6. The total Paralytic Shellfish Poison (PSP) content in the edible parts of molluscs (the whole body or any part edible separately) must not exceed 80 microgrammes per 100 g of mollusc flesh in accordance with the biological testing method - in association if necessary with a chemical method for detection of Saxitoxin - or any other method recognized in accordance with the procedure laid down in Article 12 of this Directive.

If the results are challenged, the reference method shall be the biological method.

7. The customary biological testing methods must not give a positive result to the presence of Diarrhetic Shellfish Poison (DSP) in the edible parts of molluscs (the whole body or any part edible separately).

8. In the absence of routine virus testing procedures and the establishment of virological standards, health checks must be based on faecal bacteria counts.

Algal toxins, new detection methodes

[117]
Algal toxins may be present in shellfish, molluscs and other marine and fresh water inhabitants. Global warming may spur algal blooms which highlights the importance of algal toxins detection.

Maximum levels and Detection methods are described in the Decision 2002/225 EEC.
(1) Chapter V, point 7, of the Annex to Directive 91/ 492/EEC provides that the customary biological testing methods must not give a positive result to the presence of diarrhetic shellfish poisoning (DSP)in the edible parts of molluscs(the whole body or any part edible separately).

(2) It has been scientifically proven that certain marine biotoxins such as those of the diarrhetic shellfish poisoning (DSP)complex (okadaic acid (OA)and dinophysistoxins (DTXs)) and also yessotoxins (YTXs), pectenotoxins (PTXs)and azaspiracids (AZAs), pose a serious hazard to human health when present above certain limits in bivalve molluscs, echinoderms, tunicates or marine gastropods.

(3) In the light of recent scientific studies it is now possible to establish maximum levels and methods of analysis for those biotoxins.

This Decision lays down the maximum levels for the marine biotoxins of the diarrhetic shellfish poisoning (DSP)complex (okadaic acid and dinophysistoxins), yessotoxins, pectenotoxins and azaspiracids and the methods of analysis to be used for their detection. It applies to bivalve molluscs, echinoderms, tunicates and marine gastropods that are intended for immediate human consumption or for further processing before consumption.

Maximum levels  
   
Okadaic acid, dinophysistoxins  
and pectenotoxins together 160 μg of okadaic acid equiv./kg.
   
Yessotoxins 1 mg of yessotoxin equivalent/kg.
Azaspiracids 160 μg of azaspiracid equivalents/kg.

The EU EFSA Panel recommends reduction of EU Okadaic-toxin limit

[118]
Okadaic acid (OA) and its analogues, the dinophysis toxins (DTX1, DTX2, and DTX3), together form the group of OA-toxins. These toxins are lipophilic and heat stable, are produced by dinoflagellates and can be found in various species of shellfish, mainly in filter-feeding bivalve molluscs such as oysters, mussels, scallops, and clams.

OA-group toxins cause Diarrhoeic Shellfish Poisoning (DSP), which is characterized by symptoms such as diarrhoea, nausea, vomiting and abdominal pain. These symptoms may occur in humans shortly after consumption of contaminated bivalve molluscs such as mussels, scallops, oysters or clams. Inhibition of serine/threoninephosphoprotein phosphatases is assumed to constitute the mode of action of OA-group toxins.

According to the Panel OA appears to be not mutagenic per se, but induces changes at the chromosome level and is aneugenic in vitro. The Panel noted that these effects may be related to cytotoxicity of OA.

The Panel concluded that a lowest-observed-adverse-effect-level (LOAEL) for human illness is in the region of 50 microgram OA equivalents/person, this approximates to 0.8 microgram OA equivalents/kg bodyweight (b.w.) for adults. An uncertainty factor of three was applied to extrapolate this LOAEL to a no-observed-adverse-effect-level (NOAEL) which resulted in an ARfD of 0.3 microgram OA equivalents/kg b.w.

Based on data provided by five Member States, the Panel identified 400 g of shellfish meat as the high portion size to be used in the acute risk assessment of marine biotoxins.

It was noted that a 400 g portion of shellfish meat containing OA-group toxins at the current EU limit of 160 microgram OA equivalents/kg shellfish meat would result in a dietary exposure of 64 microgram toxin. For a 60 kg adult this is equivalent to approximately 1 microgram/kg b.w. This figure exceeds the ARfD by approximately 3-fold. The Panel concluded that in order for a 60 kg adult to not exceed the ARfD, a 400 g portion of shellfish should not contain more than 18 microgram toxin, i.e. 45 microgram OA equivalents/kg shellfish meat.

The mouse and the rat bioassay are the officially prescribed reference methods in the EU for the detection of OA-group toxins. The Panel called for a validation of the phosphoprotein-phosphatase assays and liquid chromatograph-mass spectrometry (LC-MS) to replace actual methods.

Detection methods

Detection methods are described in the Decision 2002/225 EEC. Biological methods: Use mice or rats. The tests involve the death of the animals.

Alternative detection methods:

A series of methods such as high performance liquid chromatography (HPLC)with fluorimetric detection, liquid chromatography (LC)-mass spectrometry (MS), inmunoassays and functional assays such as the phosphatase inhibition assay can be used as alternative or complementary methods to the biological testing methods, provided that either alone or combined they can detect at least the following analogues, that they are not less effective than the biological methods and that their implementation provides an equivalent level of public health protection:

- okadaic acid and dinophysistoxins: an hydrolysis step may be required in order to detect the presence of DTX3, - pectenotoxins: PTX1 and PTX2, - yessotoxins: YTX, 45 OH YTX, homo YTX, and 45 OH homo YTX, - azaspiracids: AZA1, AZA2 and AZA3.

On market available kits for the detection of algal toxins

Saxitoxin (STX) is a neurotoxin found in marine dinoflagellates (algae). It is a selective sodium channel blocker. It is so strong that it is known as "TZ" chemical weapon by the U.S. military with the Lct$_{50}$ of 5 mg . min/m$^{3}$. [119] The medical importance is in relation to red tide in shellfisch because of the paralytical shellfish poisoning (PSP) food poisoning. The blocking of the sodium channel produces a flaccid paralysis that leaves its victim calm and conscious through the progression. Death is caused by respiratory failure. [119]

A Saxitoxin (PSP) algal toxin immunoassay ELISA kit is now commercially available among others: The Direct ELISA Enzyme Linked Immunosorbent Assay (ELISA) has proved to be a sensitive and rapid method for phycotoxin detection, such as:

Yessotoxin (YTX):

Yessotoxin and its analogues produced by marine algae, in particular Protoceratium reticulatum and Gonyaulax polyedra. YTX is known to accumulate in shellfish meat and is regarded as hepatotoxic and cardiotoxic when ingested above a certain level. The yessotoxins have previously been included in the diarrhetic shellfish poison (DSP) group, but the YTX chemistry and toxicology differ distinctly from the DSP toxin family. The European Commision recently placed the yessotoxins in a separate phycotoxin group, and implemented a maximum permitted level (MPL) of 1 mg YTX eqvivalents/kg shellfish intended for human consumption (Directive 2002/225/EC). [120]

Microcystins / nodularins and its congeners detection kit:

It responds to a broad range of the toxic microcystin congeners, as well as the structurally related nodularin toxins.The ELISA is derived from antibodies recognizing 6E-ADDA,the common structural feature present in the toxic congeners of microcystins and nodularins. [121]

Dominoic acid:

The amnesic shellfish poison (ASP) toxins, domoic acid (DA) and DA isomers are water-soluble neurotoxins produced by a number of marine algae, in particular by the microalgae of the genus Pseudo-nitzschia. Blooms of Pseudo-nitzschia spp. may lead to the accumulation of DA in shellfish filter feeders and other marine species. Ingestion of DA contaminated shellfish may lead to amnesic shellfish poisoning (ASP) by affecting the central nervous system, and has caused the death of both animal and human consumers in severe cases. The European Commission Directive 2002/226/EC implemented a maximum permitted level (MPL) of 20 mg DA/kg shellfish intended for human consumption. This MPL is adopted by the regulatory authorities in most other countries. This quantitative DA EIA kit detects DA in water samples shellfish and algal extracts The assay is primarily intended for use in routine monitoring of DA levels in bivalve molluscs to comply with the regulatory MPL, but is also applicable for DA quantification in the marine matrixes. [122]

Cylindrospermopsin:

It is a naturally produced toxin of several cyanobacterial strains and has been found in fresh water throughout the world. Certain strains of Cylindrospermopsis raciborskii (Australia, Hungary, United States), Umezakia natans (Japan), Aphanizomenon ovalisporum (Australia, Israel) have been found to produce cylindrospermopsin.

The production of cylindrospermopsin seems to be strain specific and not species specific. The antibody binds Cylindrospermopsin The assay sensitivity allows the determination of Cylindrospermopsin in a range of environmental samples (water, fish tissue, fish plasma, etc.). [123]

Microcystine ELISA Test:

Microcystins and the structurally related nodularins are toxins produced by cyanobacteria (blue-green algae). Acute poisoning in humans and animals can be caused by these toxins and in several cases has led to death. These toxins inhibit liver function and might act as tumor promoters. Many different structural variants (congeners) are found, with the most common variant being microcystin-LR. To protect public health, the WHO has proposed a provisional upper limit for microcystin-LR of 1 ppb in drinking water. [124]

Bacterial poisoning

Bacteria can settle on food. Due to industrialisation and globalization they can be widespread turning: The bacteria present in food can:


Examples of microorganism which spoil food:

Molds, yeasts, Escherichia coli, Proteus etc.


Examples of microorganism producing toxins:

The microorganism cited below can produce toxins when present in food and having sufficient time during storage under appropriate temperatures. In this case the microorganisms don't necessarily need to be alive when reaching the final consumer.:
Laboratory diagnosis: Sometimes the microorganism which spoiled the food are dead because the food was sterilised after deterioration. In this case chemical analysis may bring the evidence of undesired microbiological activity, such as the rise of ergosterol or rise of acidity in salads or succinic acid in egg yolk.

Bacillus cereus produces endotoxin about which there is little known. Bacillus cereus produces hemolysin and lecithinase which is not toxic and is a phospholypase.

Campilobacter jejuni produces endo- and enterotoxin.

Clostridium botulinum produces exotoxins from type A, B, C, D, E and F.
They are the strongest toxins which are known and act as neurotoxins. They inhibit the excretion of acetylcholine avoiding thus the transmission of signals from the nerve to the muscle causing paralysis comparable to the effect of curare, the poison of South American Indians.
The endotoxins which are thermo unstable are formed in canned food with a pH higher than 4.5 and about 6 month of storage.
This toxin is destroyed when food is cooked before serving.

Clostridium perfringens produces an enterotoxin formed in bad refrigerated precooked food.

Escherichia coli produces an enterotoxin under bad hygienic conditions.

Listeria monocytogenes produces listeriolysine.

Salmonella enteritides produces a heat unstable exotoxin mainly in ground meat, in eggs, in poultry, in milk powder, in chocolate and fine salads.
Salmonella typhimurium produces a heat unstable exotoxin.

Shigella dysenteriae and Shigella sonnei produce endotoxin or heat unstable exotoxins.
Shigella dysenteriae, Shigella sonnei and Staphylococcus aureus, produce thermostable toxins.

The toxins produced by Staphylococcus aureus can be classified serologically as toxin A, B, C1, C2, D, E and F.
About 19% of Staphylococcus aureus are toxin producing strains.
The toxin A and B are resistant to very high temperatures and may resist even to 20 minutes at 121,1$^{o}C$ . Often there are no sensory changes in food with staphylocoxin.

In the production of industrialised food all efforts should be made to avoid a contamination of food with Staphylococcus aureus, paying great attention to avoid handling of food by person with suppurative focuses.
Streptococcus faecalis, produces thermostable toxins
Vibrio cholerae produce enterotoxin.
Vibrio parahaemolyticus produces exotoxin.
Yersinia enterocolytica produces enterotoxin.


Examples of microorganism causing infections

:
All microorganism cited as producer of toxins of the above paragraph are able to cause infections. The microorganism must be alive and in sufficient number to cause an infection.


Staphylococcus aureus penicillin resistant

Staphylococcus aureus has experienced increasing resistance to antibiotics. The first reports from penicillin-resistant isolate, type 80/81, came from Australia and Canada in 1953, causing skin lesions, sepsis and pneumonia in children and young. The hospital and community acquired infections were treated in the 1960s with meticillin


Community-acquired MRSA (ca-MRSA)

Emerging infections with community-acquired MRSA (Ca-MRSA) picked up in public places is resistant to meticillin antibiotic. It is believed that the strain of Staphylococcus aureus may have evolved from the 80/81. Key regions in genes of community-acquired MRSA are identical to the genes of the 80/81 strain. It is therefore believed that the cMRSA strain has developed from this strain through several intermediate steps. The total genetic code differs from the hospital form.

One important toxin of cMRSA Staphylococcus aureus is Panton-Valentin-Leukozidin (PAL), responsible for the necrosis of wounds, abscesses and pustules and is determined by the gene lucks-Luke.

The Ca-MRS strain was described in USA and Canada in 1994. The germ has a specific gene "lucks-Luke" which produces a necrotic toxin causing deep necrotic wounds. These wounds must be surgically drained. Sometimes amputations becomes necessary.

German, French and Swiss samples of cMRSA are resistant to fusidin acid. This indicates the formation of a new strain of Staphylococcus aureus. Intercontinental spreading of the cMRSA is demonstrated by the finding of the MLST- Type STr with the element SCCmec type IVa in USA as well in Germany. [2190][2191]

There are nasal carriers which may spread the bacteria causing what is called a skin and soft tissue infection SSTI. Contamination occurs during body contact, smears by hand contact, crowded living conditions. Insufficient personnel hygiene.

Avoiding cMRSA: Strict personnel hygiene, Hexachlorophene Hexachlorophene should be used for hand disinfection. Avoiding crowded living conditions. Football and wrestling being a sport with body contact should take precautions on these matters.[2192]
An undersupply of vitamin complex B due to a food insufficiency or single-sided nutrition may lower immunity regarding pustules. Yeast extract or food supplement of complex B vitamines may be useful to body's defence, and may in some cases even avoid infection.

Examples of microorganism which can act as opportunists:

Candida albicans can cause infections of mouth and digestive tract by persons with weak immunological system. Yeasts being found in food should be controlled in regard of the presence of Candida albicans.


Mycotoxins

Mycotoxins are poisonous metabolites of certain moulds which can cause pathological changes in human and animals. The most important species which produce mycotoxins are Aspergillus, Penicillium and Fusarium.
Intoxication takes place through ingestion of contaminated food more seldom by inhalation or skin resorption.
Mycotoxins unlike the bacterial or algal toxins generally do not produce acute intoxication but they are known as strong carcinogenic, teratogenic with chronic activity.


Contamination with mycotoxins

Direct contamination with mycotoxins can take place when moulds grow on the food.
Indirect contamination can take place mycotoxins contaminated feed is ingested by cattle and pork. Milk, eggs and meat are examples of indirect contamination of food caused by spoiled feed containing Aflatoxins Ochratoxin A and some of the Fusaria toxins.
The direct contamination caused by on food growing moulds is of great importance on cereals, oil seeds, coffee, fruits, vegetables, spices some types of cheese like Roquefort cheese and meat products.


Aflatoxins

Aflatoxins are mycotoxins which are exclusively produced by the mould Aspergillus flavus and Aspergillus parasiticus. Of importance are the aflatoxins B$_{1}$, G$_{1}$ and G$_{1}$.

Aflatoxin B$_{1}$

Aflatoxin B$_{1}$ is the strongest carcinogenic compound known. It causes liver cancer. In food aflatoxin M$_{1}$ is sometimes present and is almost as poisoning as aflatoxin B$_{1}$

\includegraphics[width=450bp, height=200bp, angle=0]{library/Aflatox.eps}
In animal feed the most frequent aflatoxin is B$_{1}$ being often found together with Aflatoxin B$_{2}$, G$_{1}$ G$_{2}$

Mycotoxins and food chain

[754]
According to a review by Bryden 2007 mycotoxins are secondary fungal metabolites that can be produced in crops and other food commodities both pre- and post-harvest. Around 25 per cent of the world's crops are affected by moulds. Low levels of mycotoxins may produce chronic conditions with reduced growth and development, immunosuppression and cancer are chronic effects in many developing countries.

Bryden calls for a mycotoxin reduction which includes efforts of farmers, government agencies, food processors and scientists. However, a significant impact on the cost of food production is being expected.

Ochratoxin A on surface of dry sausages

[755]
Iacumin and colleagues assessed the moulds as a seasoning for sausage and aflatoxines such as ochratoxin A on the surface of sausages from northern Italy. The most frequently isolated mould strains from sausage casings were Penicillium nalgiovense, Penicillium oxalicum, Eurotium amstelodami, Penicillium olsonii, Penicillium chrysogenum, Penicillium verrucosum, Penicillium viridicatum, and Eupenicillium crustaceum. Aspergillus ochraceus. Ochratoxin A was found in 45 per cent of the samples, ranging from 3 and 18 microg/kg.

The authors report that ochratoxin A concentration was reduced to below the limit of detection by brushing and washing the sausages prior to sale. They concluded that there is no health risk for the consumer, since ochratoxin A was found only on the casings and not inside the dry meat.

Post-harvest control strategies to reduce risk of mycotoxins in grain storage

[756]
Magan and Aldred in a review of 2007 stress that contamination of cereal by moulds and mycotoxins results in dry matter, quality, and nutritional losses and represents a hazard to the food chain.

According to the authors very small amounts of dry matter loss due to mould activity can be tolerated. A dry matter loss $<$0.5% is a signal of visible moulding, mycotoxin contamination and downgrading of lots.

Important moulds contaminating dried grain are Penicillium verrucosum (ochratoxin) in damp cool climates of Northern Europe, and Aspergillus flavus (aflatoxins), A. ochraceus (ochratoxin) and some Fusarium species (fumonisins, trichothecenes) on temperate and tropical cereals.

To control the growth of moulds during grain storage modified atmospheres, fumigation with sulphur dioxide and ammonia and CO2 of $>$75% were tried. Also preservatives based on aliphatic acids, essential oils and anti-oxidants have been used storing dried grains for feed.

The authors concluded that an effective post-harvest management requires clear monitoring criteria, hygiene and the implementation of key critical control points during harvesting, drying and storage stages in the cereal production chain to minimise mycotoxin contamination during storage.

Micotoxins in African grains

[757]
According to Wagacha and Muthomi 2008 the factors that contribute to mycotoxin contamination of food and feed in Africa include environmental, such as high humidity and temperatures favour fungal proliferation, and a low socio-economic status of the majority of inhabitants of sub-Saharan Africa predisposes them to consumption of mycotoxin contaminated products. This exposes the polpulation to increased risk of immuno-suppression, impaired growth, various cancers and death depending on the type, period and amount of exposure.

The authors accentuate the synergistic effect between mycotoxin and some diseases such as malaria, kwashiorkor and HIV/AIDS. In 2004 Africa registered the greatest fatal mycotoxin-poisoning outbrek caused by contaminated maize. The authors call for intervention strategies such as early harvesting, proper drying, sanitation, proper storage and insect management, biological control, chemical control, decontamination, breeding for resistance as well as surveillance and awareness creation. Efficient, cost-effective sampling and analytical methods suitable in developing countries are needed.


Ochratoxins


Fumonisins


Trichothecens


Zearalenon


Citrinin


Patulin

Fusaria toxins

[758] Fusaria toxins is a generic term for the so called fade-toxin produced by Fusaria moulds which produce wrinkling of plant parts.
Moulds which produce fusaria toxins are:
Fusaria sporotrichiella
Fusarium tricinctum Fusaria diverisporum Gibberella zeae There are not enough official data related to fumonisin available in order to define limits of fusaria toxins in food. There is currently no official limit for fumosins in food, however,the EU has proposed a limit of 500 microgrammes per kilogram [759].The following results of tests are published:

Maize flour, polenta, maize semolina:
290 samples were analysed with following results:
58% below 30 $\mu$g/Kg
23% from 30 to 500 $\mu$g/Kg
17% $>$500$\mu$g/Kg
The highest result was 9818 $\mu$g/Kg. The group of maize products has therefore the highest concentration of fusaria toxins of all food on test.

Fumonisin was found over all in Italian maize and over 1000 $\mu$g/Kg in biological maize cultures.

Extruded products, Breakfast cereals:
The content of fumonisin of these products is much lower as found in maize:
About 25% below 30 $\mu$g/Kg
74 % from 30 to 500 $\mu$g/Kg
1% $>$ 500 $\mu$g/Kg up to 1600 $\mu$g/Kg
Sweet corn:
Fumonisin content found in sweet corn was very low.
More than 85% had not detectable amounts of fumonisin.
5% from 100 to 500 $\mu$g/Kg
Baby food. From 149 samples only 2 samples were positive to fumonisin with a maximum concentration of 55 $\mu$g/Kg.
According to the German Institute of Consumer Health Protection and Veterinary Medicine (Bundesinstitut für gesundheitlichen Verbraucherschutz und Veterinärmedizin BgVV in Berlin the contamination of cereals with Fusaria is increasing resulting in higher content of fusaria toxins in baby Food containing cereals.
The Fusaria moulds grow on the cereal stalk and transfer their toxin to the grain. The most important of these toxins are desoxynivalenol (DON)also known as vomitoxinVomitoxin), and fumonisin. They damage cells und interfere in the immune system. In wheat and maze products there were found up to 600$\mu$g/kg food.

Desoxynivalenol may coexist with Zeralenone. Desoxynivalenol causes growth depression and suppression of the immune system. 1 ppm limit in the sole feeding should not be exceeded. Zearalenone may cause fertility disturbances on the oestrogen production in pigs.

Consuming one or several meals with 20 g of fusaria contaminated cereals the tolerable daily intake (TDI) of 1$\mu$g will be surpassed. All effort should be made to discard batches of wheat, maize, and cereals with fusaria toxins. The control of the raw material should be intensified in order to guarantee low levels of fusaria toxins.
Wheat, beer, oil seeds and spices:
640 samples were analysed with no positive findings.

U.S. bio ethanol industry result in threefold mycotoxins contamination in feed

[760]
High levels of mycotoxins in maize-based ethanol co-products up to three times compared with grains, are expected by Wu and Munkvold 2008. The co-products are mostly dried distillers' grain and solubles or wet distillers' grains which are fed to livestock. The authors estimate that the mycotoxins from dried distillers' grain and solubles, mainly fumonisins, may result in loss of up to 293 million USD/y to the swine industry from weight gain reduction. Other stakeholders are also affected if mycotoxin contamination in both pre- and postharvest maize. will not be controlled.

The toxicity of the fumonisins, fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3), produced by Fusarium moniliforme to poultry was studied by Henry and Wyatt. The authors found that the 50% lethal dose for FB1, when injected into the air cell of embryonating chicken eggs, was 18.73 microg per egg. [761]

Synergistic effect of fumonisins on the toxicity of fusaric acid

[762]
Fusaric acid, only moderately toxic to the chicken egg, was found by Bacon, Porter and Norred 1995 to have its toxicity increased due to the synergistic effect of fumonisin B1 and other fusaria toxins found on corn and other cereals. The authors concluded that fusaric acid might play a role in enhanced and unpredicted toxicity in mammalian systems if it is consumed with other mycotoxins.

Fumonisins in quail rations

[763]
Butkeraitis and colleagues 2004 found that exposure to FB 1 at concentrations equal or more than 50 mg/kg could adversely affect quail performance. The authors stress the importance of controlling fumonisin contamination of quail rations.
Human tolerable Daily Intake is 800 ng/kg bw/day of FB1.

FDA sees fumonisins residues from meat and eggs not of public health concern

[764]
The FDA concluded in residue Studies in 2000 that fumonisins are poorly absorbed 'orally' in all species tested to date. Oral bioavailability averaged about 4% in swine and 0.7% in laying hens. Most of the ingested FB1and FB2 is excreted in the feces unchanged. The FDA believes fumonisin residues in meat, milk and eggs will likely not be a public health concern.

Exposure Assessment by the Australian FSA

[765]
Maize is the only commodity that contains significant amount of fumonisins (IPSC, 2000). Estimated mean dietary intakes of fumonisin B1 based on regional diets and published distributions of concentrations of fumonisin B1 in maize, indicating a mean intake of fumonisin B1 ranging from 0.2 4$\mu$4g/kg bw/day in European-type diet to 2.4 $\mu$g/kg bw/day in the African diet (WHO, 2001c). Fumonisin B1 is not well absorbed by poultry and should not contribute significantly to human dietary exposure.

Risk Characterisation:

The FSA Australia says that secondary exposure to fumonisin B1 through consumption of poultry meat products derived from poultry fed fumonisin B1-containing feed, presents a negligible risk to the consumer

Fusarium sporotrichoides

This mould grows in the surroundings of the Baykal sea and other parts of east Siberia, in the north of China and North Korea. It grows on cereals producing toxins which cause the Kaschin-Beck-disease which is a chronic osteoarthrose which begins in early childhood resulting in heavy disorder of growth, deformation of the extremities.The toxins of Fusarium sporotrichoides contract the vascular system which serves the epiphysic cartilage and metaphysis resulting in disorder in the growth of cartilage which can be observed not only in humans but also in dogs and rats which had been fed with corn covered by Fusarium sporotrichoides.


Other Fusarium:Fusarium poae, Fusarium lateratium

, Alternaria and Cladosporium fagi can produce toxins resulting in the toxic aleukie. The moulds grow on cereals specially on millet left during the winter on fields.
The disease develops in two phases : First there is a burning feeling in mouth and throat,nausea,gastroenteritis,vomit and diarrhoea.After these signs there is a leucopenia within two month which may result in sepsis. Additionally there comes to trombopenia and aplasie of red marrow. The mortality is high.The toxins are not inactivated by cooking. There are three toxins known: Sporofusariogenin, epicladosporic acid and fagicladosporic acid .

Ochratoxin A

Ochratoxin A [766] is a mycotoxin produced by moulds of genus Penicillium and Aspergillus. It is a water soluble cumarin derivate

\includegraphics[width=350bp, height=200bp, angle=0]{library/Ochratox.eps} It is found in cereals,coffee, spices and other foods.
The growth of moulds and production of ochratoxin A is speeded by high temperatures and high moisture during:
Harvest,
handling,
drying,
storage and
transport.
The daily intake of ochratoxin A in Europe is 0,7 to 4,6 ng/Kg/day.
In Germany the daily intake of ochratoxin A is estimated 0,9 ng/Kg/day.
Sources of ochratoxin A are: Cereals with 0,5 ng/Kg, coffee with 0,2 ng/Kg and beer with 0,2 ng/Kg.
Ochratoxin A is carcinogenic and genotoxic in mice and rats.
Recommended limits of ochratoxin A are:
Cereals and their derivates maximum 3 micrograms/kg
Ingredients for baby foods maximum 0,3 micrograms Coffee green or roasted maximum 3 micrograms/kg. Mixing of different charges of coffee to reduce the content of ochratoxin A is not allowed.

Ochratoxin and aflatoxins in spices

Ochratoxin A (OTA) is a mycotoxin produced by several fungal species of the genera Penicillium and Aspergillus. Contamination of food commodities, including cereals andcereal products, pulses, coffee, beer, grape juice, dry vine fruits and wine as well as cacao products, nuts and spices, has been reported from all over the world. In addition, contamination of animal feeds with OTA may result in the presence of residues in edible offal and blood serum, whereas the OTA contamination in meat, milk and eggs is negligible. Despite efforts to reduce the amount of this mycotoxin in foods as consumed, a certain degree of contamination seems unavoidable at present.
The Expert Panel of the European Food Safety Authority reported that the dietary exposures of adult European consumers to OTA ranged from 15 to 60 ng OTA per kg bodyweight per week. Tolerable Weekly Intake (TWI) of 120 ng/kg b.w. for OTA was derived by the Panel. [767]

Spices and paprika are often contaminated by aflatoxinx and ochratoxin. Aflatoxins are the only mycotoxins with legal limits for spices in the European Union. A limit for ochratoxin A is expected to be adopted soon. Limits set up by EC No. 1881/2006 regulation are 5 µg/kg for aflatoxin B1 and 10 microgram/kg for total aflatoxins, but no legal limit for ochratoxin A exist. [814]

According to Hernandez-Hierro and colleagues using a new method to analyse aflatoxins B1, B2, G1, G2 and oxratoxins based on the methoide of Rafael J. Garcia-Villanova 2004. found that aflatoxins were below these legal limits. Ochratoxin A was found with a mean of 11.8 microgram/kg. A maximum level between 10 and 20 microgram/kg is generally used in commercial transactions. [768] [769]

Past findings of aflatoxin and ochratoxin in spices:


Inactivation of ochratoxin and other mycotoxins in cereals

Heating during cooking and backing does not inactivate ochratoxin.Stored cereals can be decontaminated with an atmosphere of 2% NH3 at 20 degrees during 4 to 6 month. Regarding cost and danger which this decontamination can bear it should always tried to avoid initial contamination of food storing the cereals under proper conditions of humidity and temperature and reducing the storage time.


Harmful chemicals in hatcheries:

Residues of drugs "to prevent diseases" are found in fish meat up to 6 months after administration of the drug. Feed with animal origin with BSE material fed to routs, salmon and eels. Fish of hatcheries being fed with prion contaminated meat is a possible source of human CJD disease. Antibiotics and hormones to speed weight gain are of general concern. Drugs to combat worms are found in samples of fish meat from hatcheries.


Addictive drugs

Some vegetable substances and their derivates are toxic and create addiction, such as excessive consumption of alcohol, smoking or taking drugs.


Alcohol classified as carcinogenic substance

A German commission of the German association of research (Deutsche Forschungsgemeinschaft (DFG) [140]classifying ingredients of working materials has recently classified alcohol as carcinogenic substance[140].
As alcohol is used as cleaning agent such as window cleaning product, disinfection agent in health care and in many other working materials the recent publication has given ground to many discussions about toxicity and addiction.
As the commission was designated to classify working materials she was not allowed to extend their results to food ingredients.
It is obvious that the lobby of beverage industry makes everything possible to avoid the extension of the classification of alcohol in food as carcinogenic and addictive drug.
According to the commission alcohol is transformed in the body to acetaldehyde which on his turn damages the genotype.
The commission of the DFG created a new classification of cancerogenic substances, including alcohol in the " class of substances whose activity is so small that below a maximum concentration on working place (Maximale Arbeitsplatzkonzentration) (MAK) there is no significant risk of cancer expected." This classification includes however also formaldehyde, styrol, lindan and hexachlorbenzol at a concentration below MAK.
The former rule that any cancerogenic substance should be avoided because even a single molecule is able to start cancer is now discarded.
Toxicologists on their turn argue that alcohol is a part of the normal metabolism.
They say: "Resulting cancerogenic activity of normal metabolism is unavoidable. A small increase of the normal level of alcohol due to a limited amount of external origin does not significantly increase the cancer risk." Heavy drinking does significantly increase the risk.

Acetaldehyde in alcohol beverages and other foods increases cancer risk

[131]
Lachenmeier, Kanteres and Rehm, 2009 point out that acetaldehyde, occurs naturally in in alcoholic beverages and is the main cause of "hangover". It is also produced by the body while metabolising alcohol. There are limited evidences that acetaldehyde is an independent risk factor for cancer during alcohol consumption.

The authors identified alcohol consumption as a direct source of acetaldehyde exposure. Together with other sources such as food flavourings, tobacco and air pollution must be reduced to reduce cancer risc. The authors recommend to re-classify acetaldehyde with respect to cancer, risks assessments should consider all sources of expousure to acetaldehyde reduce the acetaldehyde content in alcoholic beverages as low as technologically possible, and to restrict its use as a food flavour additive.

Carcinogenicity of acetaldehyde

[132]
Acetaldehyde was classified as reasonably anticipated to be a human carcinogen based on the carcinogenicity in animals.

There is inadequate evidence for the carcinogenicity of acetaldehyde in humans. However, three case control studies found cancers following heavy alcohol intake, demonstrating an increased risk of these cancer in individuals with genetic polymorphisms in enzymes involved in the metabolism of acetaldehyde; these polymorphisms were associated with higher blood concentration of acetaldehyde following alcohol intake. [133] [134] [135]

The main source of human exposure to acetaldehyde is through the metabolism of alcohol. Other sources include food and other lesser extent, the air (IPCS 1995). Principal human exposure occurs with inhalation of ambient air from urban areas.

Other sources of acetaldehyde are cheese, heated milk, cooked beef, cooked chicken, and rum. It is a synthetic flavoring ingredient in processed foods, especially margarine.

Acetaldehyde has been detected in emissions from power plants that burn fossil fuels, wood, or trash. Acetaldehyde also occurs in gasoline exhaust (1.4 to 8.8 mg/m3) and diesel exhaust (0.05 to 6.4 mg/m3) (IARC 1985).


Alcohol as addictive drug

Le Monde presented at the 17.of June 1998 the report of the professor of pharmacy Bernard Roques concerning the risk of addictive drugs[136].
Bernard Roques had been appointed by Kouchner (state minister for health of the Ministry for Work and Solidarity of France ) to name a commission to screen the international scientific literature related to addictive drugs.
Bernhard Rouques is head of a section of of the National Institute for Health and Medical Research (Inserm).
The report was made under his direction.
It is based mainly on medical molecularbiological knowledge. It does not consider historical, psychological and cultural aspects of the consumption of addictive drugs.
Some drugs are still not sufficiently known, such as ecstasy which is feared to produce heavy damage of the nervous system.
Should this fear proof to be true, ecstasy must be inserted in the first group of the very hard addictive drugs.
Having some weak points, however, the Roques - Report is in his basic message correct and represents the trend towards the classification of alcohol as addictive drug.

Endomorphins control the pathway of drug and alcohol addiction

[137]
Dzung Anh Le and colleagues 2009 found that alcohol releases endogenous opioid peptides such as endorphins, enkephalins and dynorphins in the midbrain/Ventral Tegmental Area (VTA) region. Low to moderate levels of alcohol alter beta-endorphin release in the VTA region, producing the pleasant effects that likely reinforce alcohol consumption.

The euphoric or rewarding effects of alcohol is triggered by the stimulation of the natural opioid peptides in the VTA pathway, which consequently activates dopamin involved in drug and alcohol addiction. Alcohol does not release other families of endogenous opioid peptides such as enkephalins and dynorphins.

Like morphine, endogenous opioid peptides can induce analgesia and a mild euphoric effect, reduce anxiety, and may lead to a general feeling of well being.

Naltrexone [138] is currently used as treatment of alcoholism blocking opioids not specifically []. The authors, however, suggest to target specifically the endorphins in the VTA beta-endorphin pathway in treatment of alcohol abuse and craving.

Le and colleagues stress that low to moderate but not high doses of alcohol increase the release of beta-endorphin in the VTA region mediating some of the rewarding effects of alcohol. High doses of alcohol, however, induce sedative and hypnotic effects, and often increase rather than decrease anxiety and depression. The authors, therefore, recommend to stop drinking should the pleasant effects of alcohol not be experienced, otherwise negative effects may appear.

Health risks of different addictive drugs, according Rouques - Report

Harm Heroin(opiate) Alcohol Cocain
Physical addiction very strong very strong weak
Psychic addiction very strong very strong strong,changing
Neurotoxic weak strong strong
General toxicity strong strong strong
Social danger very strong strong very strong
Treatment chances yes yes yes


Harm Ecstasy psychostimulants benzodiazepine tobacco
Physical addiction very weak weak middle weak
Psychic addiction no informations middle strong very strong
Neurotoxic very strong strong 0 0
General toxicity very strong strong very weak very strong***
Social danger weak weak weak 0
Treatment chances no no no research yes
***Cancer

Harm Cannabinoides
Physical addiction weak
Psychic addiction weak
Neurotoxic 0
General toxicity very weak
Social danger weak
Treatment chances no research


The use and abuse of alcohol in pharmacy

Alcohol is used in many medicaments mainly as solvent and preservative of herb extracts, tinctures, antitussives, tonics, sedatives and many other traditional pharmaceutical preparations and last but not least it is used to improve the taste of certain medicaments. The above mentioned publications are a great challenge to pharmacy to reduce the use or ban alcohol in their preparations because of following reasons:
  1. Alcohol, even in small doses is carcinogenic Alcohol was classified as carcinogenic substance by a German commission of scientists of DFG classifying ingredients of working materials.
  2. Alcohol is an addictive drug of first category The Rouque - Report has classified the dangerousness of alcohol as strong.
  3. Alcohol should not be taken together with certain medicaments. Alcohol is listed in the incompatibility list of medicaments such as antibiotics, neuroleptics and many other. Patients under antibiotics have to avoid tonics or other additional medicaments because of their content of alcohol.


Dioxin in milk

[219] The great demand of orange juice has cause intensive farming of orange trees in Brazil. Derivates of this farming are orange oil and the peel which is dried as pellets used as cattle fodder in Germany.
These Brazilian orange peel pelletsmainly exported by "Coimbra Frutesp" company together with calcium of combustion exhaust washer was responsible to an increase of dioxin levels in milk, butter, cream and meat in Germany. The average level of dioxin in milk was 0,5 Picogramm in one gram fat. In August 1998 this level was three times as high as four month ago. In Süd Baden (Germany) milk with 4,83 Picogramm had to be destroyed as special garbage.
The orange peel pellets from Brazil used as fodder had 147 picogram dioxin per gram.
According to Abecitrus this contamination comes from the use of perchloretylene containing mineral oil used to dry the pellets. Chalk used to wash combustion gases from smokestacks had also been added to the bovine fodder. The real origin of the dioxin in the citrus pellets therefore could not be found.

Dioxin in feed
In the beginning of 2006 pig, poultry and rabbit farms in Europe were supplied with dioxin contaminated feed.

The Netherlands and Belgium announced that some of the meat from contaminated farms was sold in shops over the last two months, but no serious risk to public health was expected.

Tessenderlo, a feed ingredients company was the source of the contamination, blaming an inadequate PCB test which was not suited for testing dioxins as the cause had of the error. The first alert came from pig fat originating from Belgium with 25 times the maximum permitted concentration in pork fat.

Two defective filters at Tessenderlo Chemicals caused an error in the treatment of hydrochloric acid which was then used by PB Gelatin to extract pig fat from the process of making gelatin at PB Gelatins, a unit of Tessenderlo, a Belgian chemical company. The extracted fat was later distributed to animal feed producers such as Leroy and Algoet, it said. The level of toxicity equivalent, or TEQ, in the contaminated fat was 400 picograms per one gram of fat. The maximum acceptable level is 2 picograms.

Dioxin contaminated feed was then distributed to pork farms in Belgium, Germany and The Netherlands.The dioxin was no longer present in subsequent batches of extracted fat at PB Gelatins [262]

Recent meat pollution: Maximum levels of sum of dioxins and dioxin-like PCBs
The European Commission has adopted in 03.02.2006 new implementing legislation setting maximum levels for the sum of dioxins and dioxin-like Polychlorinated Biphenyls (PCBs) in food and feed.

Maximum levels for dioxins in food of animal origin and all animal feed have been applicable since July 2002. However, due to lack of sufficient data and scientific information at the time, no levels were set for dioxin-like PCBs. Since 2002, new data on dioxin-like PCBs has become available, and the legislation adopted today lays down mandatory limits for the combined level of dioxins and dioxin-like PCBs.

From November 2006, any food or feed in which the sum of dioxins and dioxin-like PCBs exceeds these maximum levels will not be allowed to be marketed in the EU. [220]


Food poisoning

Food may contain toxins originated by a biological activity such as mycotoxins, pollutants resulting from pollution of the environment such as dioxins and poisons resulting from human activities such as antibiotics, hormones, antihelmintica and other pesticides (lindane, carbendazim and chlopyrifos) resulting from animal breeding, mercury in fish from industrial sewage,PAC (polycyclic aromatic carbon) resulting from smoke used in food,dioxin (Polychlorated dibenzodioxin PCDD) , dibenzofuran (PCDF), Heavy metals such as arsenic, lead, cadmium, Japan had two great food poisoning:
1954 - contaminated fish with cadmium causing the "Itai-Itai disease. 1968 - contaminated fish with mercury in Minamata, resulting from industrial sewage. Mercury is found in mediteranean fish, such as tuna in concentrations up to 1 mg/Kg. Fish is the most important poison source for mercury.


Changing ecology and toxic foods

The Minamata disease in Japan: The disease was first known in Japan where 1,500 citizens of the small village Kumamoto on the shore of the Minamata bay contracted symptoms in the 1950s after an industrial release of mercury in the waters of the Minamata Bay. The Japanese victims had eaten the mercury contaminated fish.

The disease in Tapajós region: Minamata disease has been found in the fishing communities of the Tapajós River in Brazil's Amazon basin. It causes serious damage to the nervous system, resulting in uncontrollable shaking and muscle wasting. It also produces deformities in the children of offsprings.


Origin of mercury in the Amazon region:

A research team analysing the problem includes specialists in cytogenetics, ethnobotany, biogeochemistry, sociology, the environment, and forestry from the Amazonian Federal University of Pará(UFPa) in Belém, the UFPa outreach campus in Santarém, the Federal University of Rio de Janeiro, UQAM, and the Grupo do Defencia do Amazona in Santarém. Their work is supported by the International Development Research Centre (IDRC).

Gold mining:

Gold-mining activity was blamed to be responsible for the presence of mercury in the Tapajós. Independent miners mixe elemental mercury with river sediments and soil in order to extract the gold. It has been calculated that only 68 tonnes mercury/year due to poorly conducted amalgamation practice by volatilisation during amalgam distillation are liberated in the environment and is left there in the metal form. This is a small amount compared with the size of the problem.

The Minamata cases involve soluble methyl mercury, and the sufferers live hundreds of kilometers from the nearest mine.

The ecology

Slash and burn: In addition, "slash and burn" agricultural practices, leading to large-scale deforestation and erosion of soil heavily laden with natural mercury, are a major source of mercury pollution. The mercury content in wood is about 0.1 to 0.5 ppm. Slash an burn liberates this mercury.

Heavy agricultural activities such as cattle pastures, soybean, maize and cotton plantations will promote further erosion of soil which will increase mercury in the rivers of the Amazon region.

Fish from reservoirs in Northern Manitoba showed high Hg levels. Forest fires may be expected to mobilise Hg contained in biomass and redistribute it into the atmosphere either as vapor or attached to particulates.

Wild forest fires and wood combustion: Wild forest fires are estimated to release 20 tonnes of Hg to the atmosphere, which is less than 1% of natural emissions. Intentional wood combustion represents 60 to 300 tonnes of Hg about 5% of all man-made emission.

Deforestation: The deforestation by fires in the Amazon liberate about 75 tonnes of mercury in the atmosphere every year. The land is generally used for pasture and reburned in a cycle between 2 to 7 years.

Cerrado vegetation, which is mainly grass and bush, covers wide area of Brazil takes up mercury from soil and deposition by rain. Only 10% of the biomass burnt is from the deforestation and 90% is from cerrado burning.

Emission from vegetation: The formation of methylmercury called methylation, in the Amazon region differs from temperate regions due to specific sediments, floating macrophyte mats and flooded soils, together with the unique aquatic and semi-aquatic systems of the Amazon and the high mercury content of organic soils. This favorises the methylation of mercury in the region.

Mercury is present as an environmental contaminant in foods, notably in fish and seafood in the form of methylmercury. Vulnerably groups in particular select fish from a wide rage of species without consuming too much large predatory fish that tend to contain higher levels of methylmercury, such as swordfish and tuna.

The provisional tolerable weekly intake (PTWI) of methylmercury established by FAO/WHO and Food Additives (JECFA) is 1.6 microg/kg body weight. The US National Researche Council has set a maximum of 0.7 $\mu$g/kg body weight per week.
Fish as local food: Predator fish contain the highest mercury levels because it has an upper place in the food chain. Eating herbivorous fish and choosing low mercury species the intake of this metal can decrease. The local population, however, eat what they can get and this is most often the predator fish.

Flooded soil Bacteria living in oxygen-starved conditions in river sediments are believed to convert inorganic mercury into the dangerous methylated form. Flooded soils and semi aquatic sediments had higher Hg-methylation potentials than river sediments. The high net Hg-methylation potentials found in newly flooded soils are interesting, because vast areas of the Amazon are flooded in annual cycles.

As we know how dreadful the poisoning with mercury in the bay of Minamata (Japan) was all efforts should be made to avoid a total poisoning of the Amazon region. Gold mining using elementary mercury, deforestation and agriculture causing leaching of mercury should be prohibited.

Formation of Methylmercury in the North Pacifi Ocean

[226]
Sunderland and colleagues 2009 report that mercury levels of samples of water from the Pacific Ocean in 2006 were approximately 30 percent higher than those measured in the mid-1990s.

The authors found that algae from the surface fall to deeper water when they dye. There they settle, forming the particulate organic carbon which is decomposed by bacteria. Together with mercury II brought down from the surface methylmercury is produced.

Tuna from the Pacific ocean is a predator which accumulates methylmercury, accounting for 40% of the mercury ingested by humans. Marine fish and shell fish account for 75 percent of human exposure to mercury. Pregnant women who consume mercury can harm their children.

Mercury gets into the atmosphere by emissions from land-based combustion facilities. Increasing mercury content of the water of the ocean results from fallout near the Asian coasts and is transported on long range by strong circulating currents.


PCB in fish from the North Sea

According to the Belgian Ministry of Health in June 2000 the amount of PCB ( polychlorinated biphenyl) in fish from the North Sea is in some cases as high as 500 Nanogram in one gram fat.In 30% the upper limit for meat of 200 Nanogram PCB in 1 g fat is surpassed.
The Belgian Health Ministry urges the European Commission to establish an upper limit for PCB in fish.The limit used for meat does not apply for fish because of the low fat content of fish compared to meat. The upper limit for PCB in fish is therefore expected to be set much higher as 200 Nanogramm /g fat.


Poison of heated foods

HAA, Heterocyclic Aromatic Amines: They are cause by heating protein rich foods.They are carcinogenic.
PAK Polycyclic Aromatic Carbon and PAH Polycyclic Aromatic Hydrogen:Thy are formed when fat drips from grill foods and are brought back with smoke and flames contaminating the foods which are done.They are carcinogenic.
To avoid heterocyclic and polycyclic aromatic toxic compounds one should take care not to overheat foods, discard burned parts and refuse smoked food.such as smoked ham.


Hydrocyanic acid

Hydrocyanic acid HCN is a strong poison which is present in certain foods, cigarette smoke and exhaust gases from cars.
Hydrocyanic acid in food is present as hydrocyanic glycoside, nitrilosid or cyanoside. These compound can liberate hydrocyanic acid.
Acute intoxication can be cause by intake of great amount of bitter almonds and some kernels of apricots, cherry, peaches, poppy seed, lima beans and millet. A chronic intoxication can be caused by manioc.


Definitions


Chemical contaminants

: "Contaminant" means any substance not intentionally added to food which is present in food as a result of the production (including operations carried out in crop husbandry and veterinary medicine), manufacture, processing, preparation,treatment, packaging, transport or holding of such food, or as a result of environmental contamination. Extraneous matter, such as, for example, insect fragments, animal hair etc are not covered by this definition (Codex).

Definition of residues limits in food


NOAEL:

No Observed Effect Level. It is determined on the most sensitive animal and gender, being the level where no adverse effect is found.


ARfD:

Acute Reference Doses (ARfD in units mg/kg body weight) uses short-term studies for the evaluation. If the ARfD exceedes even for once only, an acute impairment of human health make take place.


ADI:

Acceptable daily intake or ADI is a measure of the amount of a specific substance that can be ingested over a lifetime without an appreciable health risk. ADIs are expressed in milligrams per kilograms of body mass per day. The ADI is determined from toxicity studies in which chronic endpoints are examined. These are often carcinogenicity, reproduction or multigeneration studies. The no observed adverse effect level established from the relevant studies is then divided by a so-called (un)certainty factor which should take into account both inter-species differences (i.e. between animals and humans) as well as intra-species differences (i.e. between individuals). The factor 100 is normally used for this. There is no immediate harm if the ADI is exceeded for once, or even for a limited time, because this limit is calculated for a lifelong exposion.


Pesticides:

Pesticides are substances which are used to prevent, destroy, repel, or mitigate any pest. This includes herbicides, insecticides, fungicides, fumigants and algaecides.
Other contaminants of food: They are found in food, water and environment.
Regulations for pesticides: Important regulations in EU are the Directive 90/642/EC setting Maximum Residue Levels (MRLs) for pesticides on raw agricultural products.
According to Directive 97/41/EC Maximum Residue Levels on processed products should be derived of the MRLs for the raw materials.

Important herbicides:Herbicides are the most widely used pesticides in agriculture.
Herbicide Use as growth control Possible harm
     
Atrazine: Weed in crops of corn, Possible carcinogen.
member of soybeans and sorghum. Harm aquatic microorganism.
steriazine group Inhibit photosynthesis Slight tendency to
    bioaccumulate
     
Metachlor: Grasses and weeds in crops Possible carcinogen.
member of beans,corn, cotton, Moderate toxic to fish.
chloracetamides peanuts, peas, potatoes, It does not bioaccumulate.
  safflower, sorghum, soybeans  
  sunflowers.  
  Perturbe protein synthesis  
     
Alachlor: Grasses and many broadleaf Restrict use because of
member of weeds in crops of beans, corn, groundwater contamination
chloracetamides cotton, milo, peanuts, peas Toxic to saltwater fish and water
  soybeans and sunflower. plants.
  Perturbe protein synthesis.  
     
2,4-D Agrotect: Stimulates plant growth Toxic to fishes and aquatic
member of the hormones (auxin), causing invertebrates. Because these
Chlorophenoxy uncontrolled cell proliferation compounds contain chlorine,
acetic acid Because these compounds they may change to dioxin.
herbicides contain chlorine, they pose  
  a risk for dioxin formation  
     
Trifluralin Grasses and broadleaf weeds in Harmful to fish and aquatic life.
Member of the a variety of tree fruit, nuts Practically non-toxic to man.
Dinitroaniline vegetables and grain crops such The enzymatic process that is
herbicides as soybeans, alfalfa and cotton. disrupted in plants is different
  Nitrosamine in some technical enough from that of humans and
  products. animals that the later experience
    no effects from the chemicals.
     
Glyphosphate: Inhibits synthesis of essential Glyphosate is probably not a
Member of the aminoacids and promotes carcinogen, group E. Possibility
Organophosphate destruction of photosynthetic for toxicity when glyphosate is
herbicides(non- pigments in foliage applied to aquatic environments.
nitrogen based    
herbicides a) Isopropylamine salt, control According to Myriam
  of weeds in broadleaf and Fernandez of the Semiarid
  grasses. Prairie Agricultural Researche
Centre in Swift Current    
  b) Sodium salt, growth regulator Saskatchewan, glyphosate-
  for peanuts and sugar cane. treated wheat appeared to have
    higher levels of Fusarium head
  c) Monoammonium salt, control blight (a toxic fungal disease)
  of weeds in tea plantation, that wheat fields where on
  orchards, rubber, plantation glyphosate had been applied.
  corn, sugarcane and forests.  
     
Dicamba: Broadleaf weeds, Chickweed, Dicamba is not carcinogenic
Member of the mayweed and bindweed in  
benzoic acid and cereals and other related crops  
and analogue    
herbicides    
     
Cyanazine and Grasses and broadleaf weeds in Cyanazine: Cancer-causing
simazine: cereals, cotton, maize, onions potential in experimental
Members of the peanuts, peas, potatoes, animals and possible risks to
s-triazine soybeans, sugar cane and wheat humans. The rat strain used was
herbicides fallow predisposed to develop the
    mammary tumours observed.
    Practically nontoxic.
     
2,4,5-T Stimulate plant growth May lead to teratogenic effects
Member of the hormones (auxin), causing in mammals.
chlorinated uncontrolled cell proliferation  
phenoxyalkanoic Because these compounds  
aciherbicideses contain chlorine, they pose a  
acid herbicides risk for dioxin formation  


Insecticide Insecticide Breakdown Remarks
groups      
       
Organophosphates Malathion Easy No residues in crops, not stored
  Ethyl-   in animal tissue.
  parathion    
  Diazinon   These pesticides affect the
      nervous system by disrupting the
      enzyme that regulates
      acetylcholine, a neurotransmitter.
      Most organophosphates are
      insecticides. They were
      developed during the early 19th
      century, but their effects on
      insects, which are similar to their
      effects on humans, were
      discovered in 1932. Some are
      very poisonous (they were used
      in World War II as nerve agents).
      However, they usually are not
      persistentin the environment.
       
Organosulfurs Tetradifon    
       
Carbamates Carbaryl Degradade They are a danger to many useful
    rapidly in the insects, especially honeybees.
    environment They affect the nervous system
      by disrupting an enzyme that
      regulates acetylcholine, a
      neurotransmitter. The enzyme
      effects are usually reversible.
      There are several subgroups
      within the carbamates
       
Formamidines Amitzaz    
       
Dinitrophenols 2,4    
  Dinitrophenol    
       
Organotins Cyhexatin    
       
Pyrethroids Permethrin   Pyrethroid Pesticides were
      developed as a synthetic version
      of the naturally occurring
      pesticide pyrethrin, which is
      found in chrysanthemums. They
      have been modified to increase
      their stability in the environment.
      Some synthetic pyrethroids are
      toxic to the nervous system
       
Nicotinoids Imidacloprid    
  (Gaucho)    
  Acetaprimid    
       
Fiproles Fipronil    
       
Pyrroles Chlorofenapyr    
       
Pyrazoles Tebufenpyrad    
       
Pyridazinones Pyridaben   No residues in crops, not stored
      in animal tissue
       
Chlorinated   Persistence - Accumulate in the fat tissue. Harms
hydrocarbons   its resistance fishes, earthworms, and robins.
(DDT) or organo   to breakdown They were commonly used in the
chlorines(Such as   in the past, but many have been
DDT, HCC,   environment removed from the market due to
Dieldrin,   is enormous their health and environmental
Toxophene     effects and their persistence (e.g.
      DDT and chlordane


Botanicals (Plant Insecticide Extracted from
extracts)    
     
     
Pyrethrum Pyrethrum Flowers of a
    Chrisanthenum. Kenia and
    Ecuador
     
Nicotine Nicotine Tobacco
     
Rotenone Rotenone Legumes
     
Limonene Limonene Citrus peel


Fumigants Insecticide Remarks
     
     
(They become gas above Methylbromide The most frequent used
40C and contain the   fumigants
halogens Cl, Br or F    
     
Ethylene dichloride Ethylene dichloride  
     
Phosphine gas (PH$_{3}$) Phosphine gas (PH$_{3}$)  


Insect repellents: Before a more edified approach to insect olfaction and behaviour was developed, it was assumed that if a substance was repugnant to humans it would likewise be repellent to insects.
Repellent Registration Agent Remarks
       
       
Benzyl benzoate Registration lost    
Indalone Registration lost    
Rutgers 612 Registration lost    
Dibutyl phtalate Registration lost    
       
MGK repellent 326 Registration lost Dipropyl It is used to expand
  Potential cancer isocinchomeronate the repellency of
  risk.New analysis   DEET, MGK 264,
  of risk   pyrethroids, and
      other active ingredients.
       
N-butyl acetanilide Registration lost   Repellent for
      military clothes
       
Dimelone Registration lost Dimethylcarbamate  
       
DEET, Delphene(r) Still registrated N,N-Dimethyl-meta- DEET is used
    toluamide worldwide for
      biting flies and
      mosquitos.No harm
      if used as labelled.

EU Regulation of maximum residue levels of pesticides

[227]
Regulation (EC) No 396/2005 establishes the maximum residue levels MRLs of pesticides permitted in products of animal or vegetable origin intended for human or animal consumption. The Regulation is applicable since September 2008.

The EFSA suggestion on some Pesticide MRLs

[228]
EFSA calles for lower MRLs where safety concerns were identified and also for substances where data available were not sufficient to substantiate the safety of the current MRL.

According to the EFSA the MRLs of active substances not authorised in the European Union should be set at the lowest level which can be measured through routine monitoring.

Pesticides Existing MRL EFSA proposed Remarks
  (mg/Kg) MRL (mg/Kg)  
       
Tetraconazole 0,02 ADI 0,04mg/Kg bw/d In apricots
    ARfD 0,05 mg/Kg bw/d  
       
Clomazone 0,01 to be maintained In rice
Mandipropamid 0,01 10,0  
Lambda-cyhalothrin 0,01 0,20 In currant
Indoxacrab 0,02 0,10  
Trifloxistrob - 0,10 Passion fruits, Kenia
Thiram 0,10 0,20 In bananas
Fluroxypyr 0,05 0,20  In leek
Teflubenzuron 0,50 1,00 In pepper
Azoxystrobin - 0,10 In passion fruit Kenya
Azoxystrobin 0,05 0,10 In turnips
Fludioxonil - 3,00 Pomegranades, USA

MRLs of concern

[228]
The EFSA found the MRLs of concern for the active substances and suggests significant reduction of the actual MRLs: Vinclozolin, procymidone, pirimiphos-methyl, oxydemeton-methyl, methomyl and thiodicarb, methamidophos, fenarimol, carbendazim, fenamiphos, ethephon, benfuracarb and carbosulfan, methomyl and thiodicarb,

Reaction of food industry

[229]
Food manufacturers say serious problems will arise from a tightening of pesticides regulations. According to the Food and Drink Federation (FDF) the reduced MRLs, the ban of some chemicals and the tighter management of pesticides may cause a reduction of 20 to 30 per cent in yields. A range of fruit and vegetables will be unable to grow in UK.
Food and Drink Federation (FDF) says that the the legislation had no scientific or practical basis.

Study complains about high pesticide MRLs in fruit juices

[230]
Study from Juan F. Garcia-Reyes and colleagues 2008, says that pesticide MRLs in fruit juices are hundreds of times higher as those for water and mineral water.

Juices and fruit-based soft drinks produced in Spain and UK were found by the authors to have the highest levels of pesticides like carbendazim, thiabendazole, imazalil and malathion, compared with products from Russia and United States which had the lowest pesticide residues in the trial. This justifies actions of the EFSA facing a reduction of pesticide levels. Fruit juices promoted as very healthy for kids need to be strongly regulated.
The authors present a new methodology to analyse pesticide residues in juices and fruit-based beverages.

The pesticide clothianidin is responsible for dying of German bees at the Rhine valley

[231]
The German Federal Institute for Risk Assessment BVL has stopped the use of the insecticide PONCHO with the chemical clothianidin widely used to fight the corn borer, following analyses of dead bees which were positive for the insecticide. The use of clothianidin to treat corn seed and rape seed was stopped by the BVL on 16.05.2008.

According to the German Minister of Agriculture Peter Haug  chlothianine plays an important role in the death of bees.

The Julius-Kühn Institute, the federal research institute for cultivated plants confirmed the presence of clothianidin in all dead bees which were examined. Experts say that special seed pneumatic machines loosened the insecticide from the corn seeds during sawing. This may be the way the insecticides was liberated and then spread by the local wind. The Institute says that it is unclear if honey of the region is contaminated or not with the pesticide which is extreme water soluble. [232]

The trademarks of the chlothianidin containing products are: [233]
Antarc 4674-00
Chinook 4672-00
Cruiser 350 FS 4914-00
Cruiser OSR 4922-00
Elado 5849-00
Faibel 4704-00
Mesurol liquid 3599-00
Poncho 5272-00

Pesticide risk assessment

The EFSA assessed the risk of several pesticides and presented its conlusions

Abamectin

[234]
According to the EFSA,Abamectin is a mixture of avermectins, containing more than 80% avermectin B1a and less than 20% avermectin B1b. These two components, B1a and B1b have very similar biological and toxicological properties. The avermectins are insecticida or antihelmitic compounds derived from the soil bacterium Streptomyces avermitilis as a fermentation product. It is used to control insect and mite pests. [235]

The acceptable daily intake (ADI) and acceptable operator exposure level (AOEL) are 0.0025 mg/kg bw/day based on the short term dog studies, whereas the acute reference dose (ARfD) is 0.005 mg/kg bw based on the acute neurotoxicity study.

The EfSA concluded that a safe use with respect to aquatic invertebrates is demonstrated only for the use in lettuce in the field (pond scenario) and the use in lettuce and tomatoes in glasshouses (ditch). For all the other uses and scenarios the risk is not acceptable without sufficient risk mitigation measures (for example no-spray bufferzones varying from 14 (stream scenario) - 18 m (ditch scenario) for applications in citrus and 2 m for the applications in tomatoes and lettuce.

The relevant regulatory endpoint for the acute risk assessment for fish was the mean HC5 based on LC50-values (= 3.08 μg a.s./L) with a safety factor of 10 = 0.31 μg a.s./L. Based on this value the use in citrus needs a bufferzone of minimal 10 m. For the other uses no additional bufferzones are necessary. For the chronic risk assessment to fish an HC5 of 0.22 μg a.s./L was agreed upon.

For the use in citrus a buffer zone of minimal 15 m is needed to get an acceptable off-field risk. For the field uses in lettuce and tomatoes this buffer zone should be 5 m.

Fluazinam

[236]
The representative formulated product for the evaluation was "Fluazinam 500SC", a suspension concentrate containing 500 g/L fluazinam. Fluazinam is the technical grade active ingredient of Allegro 500F. It is used for the control of late blight on potatoes and is temporary registered under Section 17 of the Pest Control Products (PCP) Regulations of Canada.

In the acute studies, fluazinam was harmful by inhalation, severely irritating to the eyes and skin sensitizer. The liver was the target organ in repeat dose studies with rats, mice and dogs. Some haematological changes were also observed in dogs, and the increased vacuolation of white matter in brain and spinal cord observed at high doses was demonstrated to be directly related to one impurity.

The acceptable daily intake (ADI) is 0.01 mg/kg bw/day, the acute reference dose (ARfD) 0.07 mg/kg bw and the acceptable operator exposure level (AOEL) 0.004 mg/kg bw/day. Fish was the most sensitive aquatic organisms.

Metazachlor

[237]
Metazachlor is neither a skin nor an eye irritant. It was proposed to be classified as skin sensitiser. The relevant NOAELs for subacute and subchronic exposure in rats are 110 mg/kg bw/day and 21 mg/kg bw/day. Metazachlor did not show any genotoxic potential. Liver adenomas and thyroid tumours occurred in the rat, while the mouse showed slight increases in bladder transitional cell tumours at high dose levels. Since there was no genotoxicity and clear no- effect levels for tumour development were seen in all tests, it was apparent that tumour development could be considered to involve a threshold mechanism. A classification as "Limited evidence of a carcinogenic effect" was proposed.

An ADI of 0.08 mg/kg bw/day was derived for metazachlor.

A possible transfer of soil residues to rotational crops has been identified, but under usual rotation practices with rape seed no measurable residue level above the analytical limit of quantification is expected in food commodities from rotational crops.

There is a low exposure of livestock to residues present in feeding stuff but their transfer to edible animal commodities is not expected to reach analytically measurable levels.

Fenpropimorph

[238]
Fenpropimorph is rapidly and almost completely absorbed, largely distributed, extensively metabolised and without bioaccumulation in the body. In the acute toxicity studies, the compound was shown to be harmful if swallowed and irritating to the skin. In the short term studies, the liver was the target organ and the body weight was decreased in all species.

No effects on the reproductive parameters were observed in a multigeneration study in rats, but teratogenic findings in rats and rabbits led to the proposed classification "Possible risk of harm to the unborn child".

The agreed ADI (acceptable daily intake) was 0.003 mg/kg bw/day.

Mepiquat

[239]
In mammalian toxicity tests, mepiquat-chloride is harmful to rats after oral exposure and is proposed for classification with R22 "Harmful if swallowed" (LD50 464 mg/kg bw, equivalent to 270 mg/kg bw mepiquat). The dermal LD50 of mepiquat-chloride in rats is $>$2000 mg/kg bw; mepiquat-chloride is proposed for classification as "Harmful by inhalation".

The ADI is 0.2 mg/kg bw/day based on the NOAEL of 19.9 mg/kg bw/day.

Buprofezin (NNI-750)

[240]
The Acceptable Daily Intake of 0.01 mg/kg bw/day.

Target organs in subchronic and chronic studies are liver and thyroid, showing increased weights and histological and clinical chemistry findings. A potential transfer of residues to rotational crops has been noted. In soil under aerobic conditions NNI-750 exhibits medium to high persistence. NNI-750 is as very toxic to aquatic organisms. Buffer zones of 20 m are required for use in citrus to identify low risk.

Imidacloprid (Confidor, Gaucho) risk to bees

[241]
Imidacloprid is almost completely absorbed by oral administration, does not bioaccumulate and is excreted mainly by the urine. Showing a high acute oral toxicity in mice but a low toxicity after dermal or inhalative exposure.

The acceptable daily intake (ADI) was 0.06 mg/kg bw/day

No risk for the consumer has been identified under acute or chronic exposure to residues resulting from the representative uses of imidacloprid. The representative uses are spray application in apples (northern Europe and southern Europe) and tomatoes (southern Europe) indoors and outdoors and seed treatment of sugar beet.

Overall it is concluded that the spray applications of imidacloprid pose a high risk to bees. Risk mitigation is required for the use in orchards. The risk to bees is considered to be low if the product is not applied during flowering and if flowering weeds are removed/mown before the application. However it should be noted that bees potentially foraging in the off-crop area would still be exposed via spray drift and hence not be protected by the suggested risk mitigation measure. Flowering tomato plants are visited by honey-bees and other pollinators. The risk mitigation suggested for orchards is not an option for the use in tomato since the tomato plants flower almost continuously.

The spray application of imidacloprid will cause severe impacts on non-target arthropods in the infield and off-field area. However in semi-field and field studies it was demonstrated that recolonisation of the in-field area is possible. The available data suggest that ageing of residues of 273 days is required in order not to be hazardous to larvae of Poecilus cupreus. A high risk to soil dwelling arthropods cannot be excluded for the seed treatment use. The available semi-field test with P. cupreus was conducted at too low concentrations of imidacloprid to allow a conclusion on the risk from the representative use in sugar-beet.

Tralkoxydim

[242]
Based on increased incidences of Leydig cell tumours in male rats and increases in ovarian tumours in the carcinogenicity study in female hamsters a classification as "Limited evidence of a carcinogenic effect" is proposed. Based on adverse effects on gonads observed in hamster, dog and rat in subchronic and chronic studies a classification as "Possible risk of impaired fertility" is proposed. Based on postimplantation loss and malformations observed in rats and abortions and reduced litters in rabbits, a classification as "Possible risk of harm to the unborn child" is proposed. Based on these classifications the tralkoxydim metabolite R173642 was considered relevant according to the EU guideline Sanco/221/2000-rev.10.

The acceptable daily intake (ADI) and the acceptable operator exposure level (AOEL) have been set at 0.005 mg/kg bw/d based on the effects observed in the 90- day and the 1-year dog study applying a safety factor of 100. The acute reference dose (ARfD) of 0.01 mg/kg bw has been derived from a rat developmental study.

Risk mitigation comparable to 5 m buffer zones are required to protect non- target plants outside the treated field.

Napropamide

[243]
The acceptable daily intake (ADI) is set at 0.3 mg/kg bw/day.

Epoxiconazole

[244]
The liver has been identified as the main target of toxicity. Epoxiconazole increased liver tumours and the classification as "Harmful; Limited evidence of a carcinogenic effect" was proposed. Based on the effects on reproduction seen in a two- generation study in rats (dystocia, impaired fertility, prolonged gestation and vaginal haemorrhages) it was concluded to propose a classification with "Harmful; Possible risk of impaired fertility". Based on developmental effects such as increases in number of resorptions, skeletal variations and malformations observed in relevant studies in rats and rabbits also a classification with "Harmful; Possible risk of harm to the unborn child" was proposed.

The acceptable daily intake (ADI) is 0.008 mg/kg bw/d.

Bromuconazole (Granit)

[245]
In mammals, bromuconazole oral LD50 is 328 mg/kg bw. Classification as "harmful if swallowed" was proposed. The acute toxicity by dermal and inhalation route is low (LD50>2000 mg/kg bw and LC50>5 mg/L).

Hepatocellular and cholangiocellular carcinomas in rats and hepatocellular carcinoma in mice. In both rats and mice, the tumours were likely caused by liver toxicity and subsequent cell renewal. Overall, it was agreed that bromuconazole does not have carcinogenic potential relevant to humans. Based on a dose-dependent increase of placental weight and ossification delays or supernumerary bones in a number of skeletal structures it was proposed to be classified as "May cause harm to unborn child". The ADI of 0.01 mg/kg bw/day.

Flutolanil

[246]
During the mammalian toxicology studies, flutolanil was shown to be orally absorbed up to 70% and rapidly excreted. Its acute toxicity was low, it was not irritating and did not cause skin sensitization. In short term studies, the target organ was the liver in the different species. The acceptable daily intake (ADI) is 0.09 mg/kg bw/day based on the 2-year rat study.

Benfluralin

[247]
Benfluralin has a low acute toxicity, but showed irritating and sensitizing properties. Main target organs in short term and long term studies were the liver and kidneys. Classification as "limited evidence of a carcinogenic effect" was proposed based on neoplastic changes observed in the liver of rats and mice and thyroid tumours in rats upon long term exposure.

The acceptable daily intake (ADI) is set at 0.005 mg/kg bw/day. Bananas and chemicals: United Fruit Company used pesticides like Counter and Mocap (Nematicide-Insecticide). They are being sprayed by crop planes. Honduras and Costa Rica are strongly affected by the way United Fruit handles pesticide programs and social affairs.


Chemicals used in Water treatment

Algaecides: Chelated Complex Copper Algaecide in 9 percent formulation for very effective control of a broad range of planktonic, filamentous and macro algae. Copper sulfate is also used as bactericide.


Other aquatic herbicides

Fluridone: It is a systemic herbicide that kills the entire plant and is generally nonselective since most submersed plants will be killed or affected by a whole lake treatment. It inhibits the formation of carotene, chlorophyll without the protection of carotene is then degraded by sunlight.
The contact time between the plant and Fluridone must be maintained for many weeks, otherwise the plant can regenerate.

There are no swimming, fishing or drinking water restrictions for the application of Fluridone. It is moderately persistent in water of ponds and lakes. Average half-life in pond water is 21 days and 90 days in sediments, being degraded by sunlight and bacteria. Residues may persist longer depending on the amount of sunlight and the water temperature. Fluridone is not considered to be a carcinogen or mutagen and is not associated with reproductive or developmental effects in test animals.
Treated water should not be used for irrigation for thirty days because some terrestrial plants may be damaged, even by low concentrations of Fluridone.

Glyphosate for aquatic use: It is the same active ingredient of Roundup. It has been formulated for safe aquatic use. It is very effective for emerged aquatic weed control and shoreline vegetation.

Granular 2,4-D and liquid 2,4-D Amine: It is effective for control of many submerged, emerged and floating aquatic weeds. 2,4-D kills the entire plant, what is called to be a systemic herbicideindexHerbicide, systemic, acting as stimulant of plant stem elongation. It generally targets the broad-leaved plants (dicots) such as milfoil. Most other aquatic plants are monocots (grass-like) which are not affected by 2,4-D.

Cutrine: It is a chelated copper which stays in solution to continue controlling a broad range of algae long after application. There are no water use restrictions after application. Cutrine is used to control planktonic and filamentous algae, Phythophora, diatoms Chara, Nitella and Hydrilla verticillata. It was used in trout raceways and irrigation canals and is the favourite algaecide for fish farms.It is also being used to reduce secondary bacterial or fungal infections by reducing the phytoplanctonic irritants exposing the gill surface of the fish.

Diquat dibromide: It is a quarternary ammonium herbicide for watermilfoil, Parrot Feather (Myriophyllum), Hydrilla, Water Hyacinth, Water Lettuce, Giant Salvinia and Brazilian Elodea.

Diquat is often used to dessicate potato vines to make harvesting of underground tubers easier. It also promotes peridem formation in the tubers. Diquat should not be applied to potatoes if the soil is very dry, because under such conditions, the water may move from the shoots to the tubers via xylem instead of the normal opposite direction. Tubers, close to the surface become green, treated with Diquat, they may be damaged.
Diquat is nonselective, any plant can be damaged when light and chlorophyl is present.


Inorganic Insecticides

Sulfur: Sulfur is the oldest known, effective insecticide. Sulfur and sulfur candles were burned in the past for every purpose. Sulfur is used in integrated pest management programs targeting specific pests.

Sulfur dusts are especially toxic to mites of every variety, such as chiggers and spider mites, and to thrips and newly-hatched scale insects. Sulfur dusts are also used as fungicides, such as powdery mildews.
Mercury: Very toxic.
Boron: Boric acid is being used against cockroaches and other crawling household insects.

Sodium borate: It is being used to treat lumber and other wood products to control decay by fungi, termites and other wood infesting pests.
Thalium:

Arsenics: Copper arsenate, Paris green, lead arsenate and calcium arsenate. The arsenicals uncouple oxidative phosphorylation, inhibit certain enzymes that contain sulfidryl (-SH) groups and coagulate protein by causing the shape or configuration of proteins to change.

Antimony

Fluoride: Sodium fluoride, barium fluosilicate, sodium silicofluoride and cryolite are used as insecticides. Cryolite is a relative safe fruit and vegetable insecticide used in integrated pest management programs.

Silica gels or silica aerogels: Silica dusts are light, white, fluffy and are used in combination with pyrethrum in household insect control.

Miscellaneous compounds

Pyriproxyfen: It is a pyridine.

Buprofezin: It is a thiadiazine. Both are used to control the whitfly complex, a universal problem in cotton farming.

Clofentezine: It is a member of the group of the tetrazines, used as an acaricide/ovocide for fruits, citrus, cotton, cucurbits, vines and ornamentals,inhibiting mite growth.

Enzone(r) sodium tetrathiocarbonate: It is used only on grapes and citrus applied as a water application and irrigated into the soil. It breaks down in the soil to form carbon disulfide, which acts rapidly, decomposes quickly being active against nematodes, soil insects and soil borne diseases.

Clandosan(r): It is dried, powdered, chitin protein isolated from crustacean exoskeletons and blended with urea. It stimulates growth of beneficial soil microorganisms that control nematodes, but does not have a direct adverse effect on nematodes as such.

Other contaminants

The Regulation 466/2001/EC sets maximum for other contaminants in foodstuffs. Relevant for palmoil is the maximum level of lead in fats and oils for human consumption of 0,1 mg/KG.
The regulation 2375/2001/EC sets maximum levels for dioxinsin fats and oils meant for human consumption. In this regulation the limit for dioxin is set at 0,75 pg/g for all vegetable oils.
Copper: Various copper salts, including basic copper sulfate, coppersulfatechloride, -carbonate, -hydroxide and -oxychloride are able to cause serious intoxication
Ingestion of food, water and beverages,contaminated with copper have been related. Soft drinks like orange juice dispensed in contact with chromium plated copper tubes have caused intoxication. The acid of juices can cause migration of copper from the tube as soon as the chromium surface is corroded, leaving free the copper to react.

Lead: Lead is found in the ice of Greenland dated back to the Romans and the Greeks 2000 years ago. Layers or permafrost ice are a kind of deposition of almost every environmental contaminant.

In order to reduce the consumption of lead contaminated food, it is useful to avoid the use of glazed pottery and pewter dishes to serve or store food, to avoid the storage of beverages in leaded decanters, to keep the home clean and as dust free as possible, to eat a variety of foods and to eat foods rich in calcium, iron and vitamin C so the body will absorb less lead from specific food sources that have been exposed to lead

Lead absorption is increased with iron and calcium deficiency and nutritional deficiency.
Old paint is the most important source of contamination of the environment.

Lead water pipes are even more dangerous when they transport hot water.
Tin-coated lead foil capsules on wine bottles were banned in 1996. According to a study of the Bureau of Alcohol, Tobacco and Firearms 3 to 4 percent of wines were being contaminated during pouring from lead residues deposited on the mouth of the bottle by the foil capsule.
Lead-soldered food cans were banned in 1996. Some countries still use lead-soldered cans for food and are still sold in ethnic grocery stores.

Lead was banned from house paint in 1978, and phaseout of lead in gasoline was completed in 1995.
Lead in drinking water should not exceed 5 ppb. This is the detection limit of general available methods for water analysis.


Integrated Pest Management (IPM)

IPM represents an alternative to chemical poisoning of nature promoting minimised pesticide use, enhanced environmental stewardship and sustainable systems.

A public-private partnership resulted in The National Integrated Pest Management Network (NIPMN). It provides the latest informations on IPM on the World Wide Web.
IPM research develops alternatives to pesticides, using integrated management tactics such as:
Chemicals hazard
   
   
Benzene Freshwater, life, salt water
Carbon Tetrachloride Aquatic life, cancer risk
Chlorobenene Aquatic life, cancer risk
Toluene Aquatic life, cancer risk
Vinyl chloride Packaging


Chemicals hazard
   
   
Pentachlorphenol Aquatic life, Human consumptin
Acrylamide Human consumption
   
Polychlorinated Aquatic life, human consumption, cancer risk
Biphenyls  
   
2,3,7,8-TCD Aquatic life, human consumption, cancer risk
(dioxin)  


Herbicides in rainfall

Agricultural practices in the United States require extensive use of herbicides for producing three principal row crops-corn, soybeans, and grain sorghum.

Approximately 140 of the 218 million kilograms of herbicides used at the beginning of the 90th were mainly atrazine and Alachlor applied in the upper Mississippi River drainage basin, the Corn Belt of USA which is parts of Illinois, Indiana, Iowa, Ohio, Minnesota, and Nebraska.

They came into the atmosphere by volatilisation and entrainment on dust particles. Winds transported them to the region of the Great Lakes. The rainfall in this region contained atrazine and Alachlor as most frequent herbicide.

The degradation of atrazine in water is about only 1 % per year.Therefore this herbicide accumulates in the lakes.


Biopesticides

Biopesticides are certain types of pesticides derived from natural materials
Classes of biopesticides:
Microbial pesticides: They consist of a microorganism, such as bacteria, fungus, virus or protozoans as the active ingredient. Important microbial pesticides are strains of Bacillus thuringiensis which produce mixtures of proteins killing specificly one or a few related species of insect larvae. While some Bt's control moth larvae found on plants, other Bt's are specific for larvae of flies and mosquitoes. The target insect species are determined by whether the particular Bt produces a protein that can bind to a larval gut receptor, thereby causing the insect larvae to starve.

Plant-Incorporated-Protectans (PIPs): They are pesticidal substances that plants produce from genetic material that has been added to the plant, such as genes from Bacillus thuringiensis. Those who deny genetic engineering do not use plant-integrated-protectans.

Biochemical pesticides: Biochemical pesticides are substances, such as insect sex pheromones, that interfere with mating, as well as various scented plant extracts that attract insect pests to traps by non-toxic mechanisms. Conventional pesticides, by contrast, are generally synthetic materials that directly kill or inactivate the pest.


Conventional pesticides

Atrazine: It is the most widely used pesticide, controlling broadleaf and grassy weeds. It was registered in December 1958. Its estimated production is 76 to 85 million pounds annually.
It is used in the culture of corn, sugarcane, residential lawns, sorghum, guava, hay, macadamia nuts, pasture, winter wheat and on non-agricultural sites.

Atrazine is not likely to be carcinogenic to humans, however, it has been associated with imbalances in hormone levels in laboratory animals, possibly disrupting reproductive and developmental processes.

Azinphos-methyl: It is an organophosphate insecticide used on fruits and vegetables. It is a risk to children ages of one to six years and agricultural workers. It can over stimulate the nervous system causing nausea, dizziness, confusion, and at high exposures, respiratory paralysis and death.

Desert Locust

[2]
Yemen is facing its worst Desert Locust outbreak since 1993, FAO warned on 6 June 2007. An intensive survey and aerial control campaign using helicopters needs to be mounted to avoid massive locust infestations and serious damage to food crops.

If locust infestations are not controlled in time, agricultural crops in Wadi Hadhramaut and other areas including the Sana'a highlands will be at risk.

Locusts are migratory grasshoppers that often travel in vast swarms. A Desert Locust lives about three to five months. The life cycle comprises three stages: egg hopper and adult.

Eggs hatch in about two weeks, hoppers develop in five to six stages over a period of about 30-40 days, and adults can mature within three weeks. Swarms can travel from 5 to 130 kilometres or more in a day with the wind.

A Desert Locust adult can consume roughly its own weight in fresh food per day about two grams. A very small part of an average swarm eats the same amount of food in one day as about 500 people.

Contaminants in food

[221]
The European Commission noted on the 7. June 2007 what has been undertaken to reduce contaminants in food. According to the definition adopted by the EU, contaminants are substances that have not been intentionally added to food. These substances may be present in food as a result of the various stages of its production, packaging, transport or holding. They also might result from environmental contamination. Some contaminants have already studied by food safety authorities, such as mycotoxins (aflatoxins, ochratoxin A, fusarium-toxins, patulin), metals (cadmium, lead, mercury ,inorganic tin), dioxins and PCBs, polycyclic aromatic hydrocarbons (PAH), 3-MCPD and nitrates Ongoing investigations are:

Acrylamide - The Commission will collect data concerning surveys of acrylamide made by member states over three years between 2007 and 2009. [222]

Organotins - chemicals which can be found in water systems due to their presence in paints as anti-biofouling agents e.g. used on the hulls of ships and marine apparatus. The European Food Safety Authority (EFSA) has issued an opinion on the health risks to consumers associated with exposure to organotins in foodstuffs.

Scientific Committee on Health and Environmental Risks (SCHER) has recently adopted an opinion on the risks to health and the environment associated with the use of 4 organotin compounds. In this opinion food and non-food exposure routes were assessed. More informations are available at the EFSA opinion, SCOOP Report. [223]

Ethyl carbamate: It is a compound that can naturally occur in fermented foods and beverages. It often occurs in alcoholic beverages (in particular stone fruit brandies). Ethyl carbamate is formed by ethanol and certain precursors in the fruit mash under the influence of light during the distillation process. EFSA is currently collecting data on the presence of ethyl carbamate.

Furan: Furan has been identified in a number of foodstuffs that undergo heat treatment such as canned and jarred foodstuffs. A report on provisional findings on furan in food has been compiled by EFSA. [224]
EFSA is currently collecting more data on furan .e.g. on its mode of formation, levels in food and toxicity. [225]

Furan in heat treated foods

[249]
Furan was found by the FDA in a number of foods that undergo heat treatment, such as canned and jarred foods. The presence of furan is listed in the Department of Health and Human Services Report on Carcinogens and is considered possibly carcinogenic to humans by the International Agency for Research on Cancer .

Mechanisms of Formation
The primary source of furans in food is thermal degradation and rearrangement of organic compounds, particularly carbohydrates. A variety of experimental systems, including heating of sugars in the presence of amino acids or protein and thermal degradation of vitamins produced furans in food. Furan producing systems are: Thermal degradation of glucose; thermal degradation of glyceraldehydes, D-Erythrose, pentosans, hexoses, and polysaccharide; and a lactose-casein browning system. The specific mechanism that produce furan are unknown.

Among the model systems studied, ascorbic acid had the highest potential to produce furan, followed by glycolaldehyde/alanine $>$ erythrose $>$ ribose/serine $>$ sucrose/serine $>$ fructose/serine $>$ glucose/cysteine. [250]

Intake of dioxins and furans can take place through breathing contaminated air, drinking contaminated water or eating contaminated food. About 90% of exposure to dioxins and furans is from eating contaminated food.

Dioxins and furans can build up in the fatty tissues of animals. This means that eating beef, pork, poultry, fish as well as dairy products can be a source of exposure.

Recommendations EPA

[251]
The U.S. EPA has set a limit of 0.00003 micrograms of 2,3,7,8-TCDD per liter of drinking water (microg/L). The Food and Drug

Administration recommends not eating fish and shell fish with more than 50 parts per trillion (50 ppt) of 2,3,7,8-TCDD.

Foods which may contain furan

[252]
During heat treatment furan may be formed in foods rich in carbohydrates such as babyfoods with banana or potatoes, other foods likee fruits, vegetable juices, canned vegetables, coffee cocoa, bread, grilled meat and smoked foods. Furan is present in the smoke of cigarettes in concentration of 8,4 microgram in 40 ml breath (Egle et al. 1979)

Furan is the 1,4 -Epoxy-1,3-butadien, it is also called Furfuran, Oxol, Tetrol, Divinylenoxid, Oxacyclopentadien. Furan is not dibenzo-furan which is part of a group of dioxin-like substances called furane.

The CONTAM Panel Report on furan

[253]
Taking into account all the presently available data on the mode of action of furan, the Panel concluded that the weight of evidence indicates that furan-induced carcinogenicity is probably attributable to a genotoxic mechanism. However, chronic toxicity with secondary cell proliferation may indirectly amplify the tumour response.

From the presently available data it appears that there is a relative small difference between possible human exposures and the doses in experimental animals that produce carcinogenic effects, probably by a genotoxic mechanism. However, a reliable risk assessment would need further data on both toxicity and exposure.

Control of locusts

[254]
The Desert Locust is a difficult pest to control. Early warning and preventive control is the strategy adopted by locust affected countries in Africa and Asia to try to stop locust plagues from developing and spreading .FAOs Desert Locust Information Service (DLIS) in Rome, Italy monitors the weather, ecological conditions and the locust situation on a daily basis. Results and warnings are available on the FAOs Locust Watch web site. FAO also provides information.

An ecological method to control Desert Locust is with natural enemies. These include predatory anand parasitic wasps and flies, predatory beetle larvae, birds and reptiles, but are not sufficient to control great swarms Another old African method is by putting poisonous or aromatic plants next to the crop they are trying to protect.

Organophosphate insecticides

[254]
At present the primary method of controlling desert locust infestations is with organophosphate insecticides applied in small concentrated doses by vehicle-mounted and aerial sprayers. The insecticide must be applied directly to the insect.

Biological control of locusts:

Biopesticides include fungi, bacteria, neem extract and pheromones. The effectiveness of many biopesticides equals that of conventional chemical pesticides. They are usually harmless to other creatures and the environment.

Biological control of locusts

[254]
A biological control product is Green Muscle. It is based on a naturally occurring entomopathogenic fungus which is a fungus which infects fungus Metarhizium anisopliae var. acridum This fungus infects many groups of insects. It is harmless to humans and other mammals and birds. It is recommended for use mainly against hoppers, the wingless early stages of locusts. it allows the natural enemies of locusts and grasshoppers to continue their beneficial work.

Biopesticides are also safer to use in environmentally sensitive areas such as national parks or near rivers and other water bodies.

Green Muscle was developed under the LUBILOSA project Pathogens have the advantage that they can be produced in artificial culture in large quantities and be used with ordinary spraying equipment. The fungal spores are sprayed in oil. Oil-based formulations allow the application of fungal spores under dry conditions such as found in deserts.

Most insects living near the soil have evolved natural defenses against entomopathogenic fungi like M. anisopliae. This fungus is therefore locked in an evolutionary battle to overcome these defenses, which has led to a large number ofstrains that are adapted to certain groups of insects. Some strains are so specific that they have attained variety status, like Metarhizium anisopliae var. acridum, which almost exclusively infects grasshoppers. The use of Metarhizium anisopliaein the control of malaria mosquitos coating mosquito nets or cotton sheets attached to the wall with them.is under investigation. [255]


Antimicrobial agents

Antimicrobial agents are substances used to destroy or suppress the growth of harmful microorganisms whether bacteria, viruses, or fungi on inanimate objects and surfaces. More than 8000 antimicrobial products, containing about 300 different active ingredients, are sold as sprays, liquids, concentrated powders, and gases, ending in the environment.


Types of Antimicrobial Products

Non-public health products: are used to control growth of algae, odour causing bacteria, bacteria which cause spoilage, deterioration or fouling of materials and microorganisms infectious only to animals. They are used in cooling towers, jet fuel, paints, and treatments for textile and paper products. Public health products: They are intended to control microorganisms infectious to humans in any inanimate environment. The more commonly used public health antimicrobial products are:

Sterilisers (Sporicides): Used to destroy or eliminate all forms of microbial life including fungi, viruses, bacteria and their spores.
The term Sporicide is to be considered synonymous with "Steriliser". Sterilisations used to control infection and is widely used in hospitals on medical and surgical instruments and equipment. Types of sterilisers include steam under pressure (autoclaving), dry heat ovens,UV rays, low temperature gas (ethylene oxide), and liquid chemical sterilants. Gaseous and dry heat sterilisers are used primarily for sterilisation of medical instruments. Liquid sterilants are primarily used for delicate instruments which cannot withstand high temperature and gases.

Disinfectants: Disinfectants are used to destroy or inactivate infectious fungi and bacteria but not necessarily their spores. There are the type for hospital and the type for general use

Hospital type disinfectants: They are the most critical to infection control and are used on medical and dental instruments, floors, walls, bed linens, toilet seats, and other surfaces.

General disinfectants: They are the major source of products used in households, swimming pools, and water purifiers.


Sanitizers:

Sanitizers reduce, but not necessarily eliminate, microorganisms from the inanimate environment to levels considered safe. Sanitizers include food contact and non-food contact products. The food contact sanitizers are used to rinse surfaces and cooking utensils, as well as equipment of food-processing plants, and eating and drinking establishments. Non-food contact surface sanitizers include carpet sanitizers, air sanitizers, laundry additives, and in-tank toilet bowl sanitizers.

Pesticides

Chromated Copper Arsenate: This denomination is used for mixtures consisting of three pesticidal compounds (arsenic, chromium, and copper) which are registered for wood preservative uses.

The majority of the wood used outdoors is pressure-treated with this wood preservative to protect it from rot and decay. Heavy contamination of the soil of playgrounds with arsenic (up to 177 ppm) coming from wood treatment with chromated copper arsenate.The standard of risk for residential cleanup is 7.6 parts per million according to the Michigan's Department of Environmental Quality.

Arsenic is a known human carcinogen. A substitution for chromated copper arsenate should be developed. Sealants which stop the arsenic from coming out of the wood are not a good alternative, because arsenic remains in the environment.

Arsenic in rice and their products

[256]
Richard Stone reported in June 2008 that rice and products such as rice bran and rice crackers have elevated arsenic levels which increase cancer risk. Rice fields are recently extended to regions where arsenic pesticides had been used in cotton plantations. Rice accumulates arsenic ten-fold compared with wheat and other cereals.

The World Health Organisation stipulates a maximum level of 10 $\mu$g/litre of arsenic for water. China regulates arsenic in food, setting levels (0.15 $\mu$g/kg). In relation to shellfish US FDA recommends a tolerable daily intake of inorganic arsenic of 130 $\mu$g.

In 2007 high levels of arsenic were found in in a rice porridge sold in UK supermarkets for weaning infants, exceeding 150 $\mu$g of inorganic arsenic/kg. Rice bran from Japan and USA was also found to have high levels of arsenic.

The FSA, however, wrote in May 2008 that the organic form of arsenic is less harmful but the inorganic form is known to cause cancer. While the concentration of total arsenic in rice is low, about 50% of it is present as inorganic arsenic. Recent studies compare intakes of arsenic from baby food with standard of drinking water. It must be decided which level of arsenic in food should be accepted. In this case the FSA believes the amounts of arsenic found are of no concern, because the arsenic is naturally present, it is likely to have always been present in rice and recent studies show that the intake levels are not increasing.

Currently, the Agency does not feel that these reports require any changes in consumption of rice or rice products for either adults or children. [257]

Arsenic in groundwater in India

[258]
High arsenic content of water and some crops of rice are of local relevance. According to Dr.Ashok Ghosh there are regions of four districts of India facing heavy contamination of ground water and irrigation water with arsenic. The districts are Patna, Bhojpur, Vaishali and Bhagalpur. Bihar has is experiencing the highes contamination of its ground water. Hand pump water was found with up to 1861ppb arsenic. This justifies the need for expanding the study area to the remaining area of Bihar state, says Dr.Ghosh. Serious skin diseases and other ailmernts due to high arsenic in water, symptons of arsenicosis, were reported from the affected regions. [259]

Genetic engineering of rice to reduce arsenic in foods:

Zhu Yong-Guan of the Research Center for Eco-environmental Sciences in Beijing, China to investigate ways in which farm practices could be changed, for instance by growing paddy rice in raised beds or engineering rice plants to shed arsenic. Other studies include aquaglyceroporins which are proteins which transport arsenic and other metals across cell membranes. A transgenic rice with modified aquaglyceroporins settings or inclusion of bactzerial enzime, arsenite S-adenosyl-methyltransferase, may reduce final arsenic content of rice.

Other strategies are being suggeste, like blending high arsenic rice with low arsenic rice from other regions of the world is being suggested. Researchers suggest to grow upland rice on dry land which absorbs far less arsenic from the soil, or to grow rice aerobically in raised beds to reduce the mobilisation of soil arsenite.


Agent Orange

Approximately 20 million gallons of the herbicide Agent Orange was used in Vietnam from 1962 to 1971 to defoliate trees under which the enemy was hiding or some killed crops to deprive Viet Cong and North Vietnamese troops of food. It was a mixture of:

2,4,5-trichlorophenoxyacetic acid (2,4,5-T), contaminated with dioxin,
2,4-dichlorophenoxyacetic acid (2,4-D),
cacodylic acid and picloram.

2,4-D and 2,4,5-T were developed during World War II for destruction of the enemies crop but came not in use. With the beginning of its production in 1940 it was used in large scale by farmers, foresters and homeowners to control weed and brush. A byproduct of the industrial production of 2,4,5-T was a dioxin which was the toxic cancer causing component of the Agent Orange.

Effects of Agent Orange on mangrove Trees: Besides the cancer causing effect of Agent Orange the herbicide killer about 36% of the mangrove trees in the Southern part of South Vietnam were killed because of their high sensitivity to it. The mangrove trees will not return without extensive reseeding.

Persons exposed to herbicides similar to Agent Orange or some of its components have a high risk of Chronic LymphocyticLeukaemiaa,Diabetes, Hodgkins disease, multiple myeloma, prostate cancer, lung cancer. Highest use was in the period 1962-1971 for agricultural purposes, on lawns and turf, along rights-of-way, on private forests, to kill aquatic plants, and for other purposes. Almost everyone all over the world was in contact with this poison, a careless lack of knowledge.

Other herbicides were sprayed in Vietnam varying according the season, different vegetation and environment.

Other chemicals used for military activity: During 2000, the US Congress planned to use the fungus Fusarium as a biological control agent to kill coca crops in Colombia and another fungus to kill opium poppies in Afghanistan. These plans were dropped because the rest of the world could see it as unilateral biological war.

Sanho Tree is the director of the Drug Policy Project at the Institute for Policy Studies, Washington,DC says the US has supplied tens of thousands of gallons Roundup to the Colombian government for use in aerial fumigation of coca crops by crop dusters to dump glyphosate over hundreds of thousands of acres in one of the most delicate and bio-diverse ecosystems in the world.

Late sequelae of agent orange defoliant herbicide in Vietnam made by Monsanto and Dow

[260]
The Vietnamese Association of Victims of Agent Orange/Dioxin (VAVA) will launch their appeal at a federal court opening on 18 June 2007 in New York against 37 US companies that produced Agent Orange, a poisonous defoliant that the US army showered forests and rice paddies with during its war against Vietnam.

VAVA presented a claim against 37 companies who produced Agent Orange, among them being Dow Chemical and Monsanto, in January 2004. The claim specifies that the production of dioxin and other toxic substances used as weapons by US military forces against Vietnam has a direct link with extreme health problems and deformities of three millions of people in this country.

In 2005, VAVA's initial case was rejected as the court determined there were no legal grounds for the trial.

The US has compensated its own army veterans who have developed certain cancers since serving in Vietnam, but little has been done for the Vietnamese. In 1999, 20,000 South Koreans filed a lawsuit in Korea and in January 2006, the Korean Appeals Court ordered Monsanto and Dow to pay $62 million in compensation to about 6,800 Koreans.

Hai Bluhm a Vietnamese person seeking asylum in Potsdam, Germany is heavily signed by agent orange. He is one of the witnesses which will be heard by the court. The appeal is launched against the chemical factories of the defoliant because the constitution of the united States of America does not allow in this case action lawsuit to be been filed against the US Government. [261]

Reduction of input of pesticides: The government of Ontario launched a pesticide reduction program in 1982 based on rotation of the fields between corn and soybeans. The use of pesticides went down by 40 percent. At the same time the use of pesticides in USA increased by 10 percent. More effort should be spent in order to reduce the use of pesticides developing farming knowledge.


Pollutants in milk and dairy products

Pesticides in milk have their origin in animal feed. There is much being done in Europe regarding safety of feed.
The fat soluble pesticides like polychlorated hydrocarbons can contaminate easily milk. Pesticides such as insecticides, fungicides, herbicides, hexachlorobenzene (HCB) and isomers of hexachloro cyclohexane (HCH) are used in agriculture or are found on the fields.
Low concentration of pesticides in animal feed store in the body of animals and can be detected in the milk in high level.

Polychlorated biphenyl(PCB): Chlorated hydrocarbon such as Polychlorated biphenyl (PCB) were used in the past in transformers, refrigerators, in hydraulic oil and as all round chemicals.

Its level in milk has decreased after the use of PCB has been reduced. Other chlorated hydrocarbons such as polychlorated dibenzodioxine ( PCDD ) and polychlorated dibenzofurane ( PCDF ) are also present in the human milk and in the milk of cows, but not as high as Chlorine hydrocarbons ( HCB, DDT and PCB ).

The identification of polychlorinated dibenzodioxins and dibenzofurans requires expensive equipment. Many countries with low budge neglect the surveillance of these contaminants.

Use of DDT for indoor spraying

[2265]
In September 2006 WHO issued a clear statement outlining their position on indoor spraying with long-lasting insecticides such as DDT, specifying where and how spraying will be implemented in accordance with WHO guidelines, and how they will provide all possible support to accelerate and manage this intervention effectively.

According to Dr Arata Kochi, Director of WHO's Global Malaria Programme, one of the best tools against malaria is indoor residual house spraying DDT.

Indoor residual spraying is the application of long-acting insecticides on the walls and roofs of houses and domestic animal shelters in order to kill malaria-carrying mosquitoes that land on these surfaces.

The Presidents Malaria Initiative (PMI) is a five-year initiative to control malaria in Africa. Announced by President Bush on June 30, 2005, it is a collaborative U.S. Government effort led by USAID
The PMI used initially pyrethroids, however, Anopheles funestus developed resistance to this insecticide and the indoor residual spraying moved to DDT. Only Mozambique refused the use of DDT and accepted the use of carbamates such as Bendiocarb and Propoxu. [2264]

Insecticide-treated mosquito nets
The use of bed nets has long been encouraged by WHO, the recent development of "long-lasting insecticidal nets" (LLINs) has dramatically improved their usefulness. Unlike their predecessors, the long-lasting nets need not be re-dipped in buckets of insecticide every six months as they remain effective for up to five years without retreatment.

Uganda and DDT [2265] The health minister of Uganda Jim Muhwezi has told the Parliamentary Committee on Social Services that government will soon start indoor spraying of DDT. Uganda is proposing that DDT is only used indoors, and not outdoors. It will be sprayed onto the inside walls of houses and is expected to dramatically reduce the number of mosquitoes in residential accommodation. Consequently the incidence of malaria in Uganda should fall dramatically.
However outdoor spraying of DDT was halted in Europe and America in the 1960s after it was discovered that it can accumulate in the food chain.

The one proviso should be that government puts in place strict safeguards to ensure that no outdoor spraying of DDT takes place in Uganda. If this happened and was detected by the European Union, exports of agricultural and horticultural products could be banned.

Chlorpyrifos

The indoor exposure of young children to the semivolatile pesticide chlorpyrifos is higher than previous estimations. Gurunathan and colleagues found that the pesticide continues to accumulate on children's toys and hard surfaces 2 weeks after spraying. [2262] [2266]

According to a joint agreement between the U.S. EPA and the registrants of chlorpyrifos-based products Chlorpyrifos and products based on in 1997, a number of indoor uses of the pesticide, including broadcast spraying and direct uses on pets will be phased out. While crack and crevice treatment of insects (such as cockroaches and termites) by chlorpyrifos will still continue, it appears prudent to explore other insect control options, including the use of baits, traps, and insect sterilants and growth regulators.

Mycotoxines (aflatoxins): Aflatoxins such as aflatoxin B1 may be present in ground peanuts or cotton seeds come in through animal feed. The cows changes the aflatoxin B1 to aflatoxin M1.

This is why animal feed should be protected against deterioration. Feed with mould should be discarded.

Heavy metals: Heavy metals such as lead, cadmium and mercury are of small importance because their concentration in milk is low due to their low solubility. All efforts should be made to avoid contamination because milk is used to feed children and dairy products such as cheese or yoghurt are consumed in large scale. Concentration in human fat depot takes place

Contagious diseases: Foods bearing pathogenic bacteria viruses or other agents of diseases like BSE should be avoided through rigorous epidemiological measures.

Contaminated or spoiled food should not be fed to animals. Often spoiled food and cereals are given to the production of animal feed in order to get rid of them.

Radioactive pollution of milk: In Europe the nuclear accident of Tschernobyl had caused a considerable increase of radioactivity in milk and milk products in 1986.

The amount of radioactive material which was liberated into the atmosphere was several times the amount liberated by the Hiroshima bomb in 1945. Immediately after the accident due to west bounded winds there were the following radionuclides found in West Europe: Iodine-131, cesium-134 and cesium-137 and a small amount of Strontium-90.

Strontium-90 is still very high in Brazil nuts of the Amazon region originated from nuclear bomb test in Nevada, in the forties. The radioactive pollution was carried through the Stratosphere and came down as fall-out in the rain forest.

These incidents show how carefully radioactivity should be handled. In milk the nuclides are concentrated in the whey and remain there. That is why whey powder was highly contaminated causing headlines. The contamination with Strontium 90 in butter was low.
In whey powder due to the concentration, radioactivity can increase from 200 Bq/liter to 7.200 Bq/kg. In 1986 500 tons of whey powder were discarded in Germany having high radioactivity resulting from the concentration of cesium. In cheese the remaining cesium amount is very low.
After some weeks only cesium -134 and cesium -137 were left.

Low levels of radioactivity are told to increase the efficiency of the DNA repair-system increasing the activity of the immune system. This is not valid for nuclide in food because they are deposited in bones and organs and with the time this material is being concentrated in the body. Damage of cells is than possible.
Therefore radioactivity in food must be kept as low as possible.

Pollutants in milk and dairy products in Bavaria,(South of Germany): The pollutants in milk and dairy products are being controlled over 25 years by the laboratory MUVA Kempten (Veterinary medical analytical office of Kempten). This laboratory has monitored the organochlor-pesticides, PCB, halogenated solvents and heavy metals.

The results of these analyses made it possible to find the cause of the contamnation and helped to reduce it. At the moment most of the former pollutants of organochlor-pesticides have fallen below detection level in milk from Bavaria. Only lindan is still increased.

This is an example of handling the environment problems making long term monitoring of food with the cooperation of the laboratory, the agriculture and the industry.

One important concern of the laboratory is the contamination of food caused by migration of packing components into the food, such as styrol from polystyrol, dioxines from cardboard, plasticiser, heavy metals, nitrosamines from rubber, and (Bisphenyl-A-diglycidilether), problems which come from coating of tin cans. About 70% of canned food were found to be contaminated with BADGE and BFDGE (Bisphenol-A-diglycidilether) according to the French magazine "test achat". Heavy contamination was found in cans containing fish and foods with high amount of acid like lemon, vinegar or tomatoes.

BADGE / BFDGE: The European Commission has completed in early 1999 a study concerning the safety of BADGE. According to this study there is no danger coming from BADGE. Therefore the Commission decided to rise the maximum allowed amount of BADGE in foods from 20 microgram in one kilogram up to 1 milligram in one kilogram food.

This is intended only for tin cans coated with plastics. As there are no limits established for coatings with clear varnish, many countries use this high value also for varnished cans. The toxicology of BADGE and the catabolic products of BADGE and BFDGE are still unknown. Discarding the immersion brine can reduce Badge and BFDGE of canned foods.

The cooperation between official supervision of food, agriculture and industry has brought good results in research and improvements since repressive supervision had been changed to open discussion and mutual good will of all parts engaged in the long way from farming to the consum.

Levels of dioxins and environmental pollutants PCBs in UK food: According to the survey of 2001 the total amount of dioxins in the diet has fallen by around 50 per cent for all age groups since the last survey in 1997.

Exposure to dioxins in food has fallen by around 85 per cent over the last 20 years and continues to fall steadily.

Polychlorinated biphenyls (PCBs) tend to accumulate particularly in foods containing fat, such as milk, meat, fish and eggs. Any potential health risks will only come from long term exposure to dioxins and dioxin-like PCBs at the highest levels found in foods.

PCBs WHO TEQ/kg WHO TEQ/kg UK Tolerable Daily Intake
  bw/day bw/day (TDI)WHO TEQ/kg
  1997 2001 bw/day2001
       
       
average adult 1,8pg 0,9pg 2pg
Children 1,6-5,1pg 0,7-2,3pg Source: FSA UK


Only 1 per cent of adults are now estimated to exceed the TDI for dioxins from the average diet, falling from 35 per cent in 1997. The percentage of schoolchildren likely to exceed the TDI for dioxins from an average diet has also fallen considerably - from 62 per cent in 1997 to 10 per cent in 2001. The percentage of toddlers likely to exceed the TDI for dioxins is now 37 per cent, falling from 97 per cent in 1997.

Dioxin and dioxin-like PCBs in fish oil supplements: The FSA controlling 33 products of fish oil, found a wide range of concentration of dioxins.

According to the FSA, exposure to dioxins has decreased by 75 per cent over the past 20 years. Consumers should not avoid fish oils as a result of the survey, since the benefits of the product far outweighed the potential risks if taken in the right amounts.

The Food Standards Agency reviews fish advice on account of sustainability

[2267]
The FSA says that it is reviewing its advice on eating fish in relation to the sustainability of some types of fish to cope with the concern about the sustainability of fish stocks and the wider environmental impact of fishing and fish farming.

The Agency's current nutritional advice remains that consumers should be eating more fish and should be aiming to eat at least two portions of fish a week, one of which should be oily. There may be low levels of pollutants in oily fish that can build up in our bodies, so pregnant and breastfeeding women, girls and women who one day may have a baby should not eat more than two portions of oily fish a week. Others can eat up to four portions a week.

Organohalogens and vitamin A metabolism: Contamination of foods by organohalogens, in particular dioxins (PCDD and PCDF) and dioxin-like PCBs (polychlorinated biphenyls) PCBs are of concern. The most toxic dioxin is TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin).

Dioxins and dioxin-like PCBs affect the skin, the liver, and the nervous system but also have some effect on cancer development, disturbance in the immune system and on the growth and development of the foetus.

Dr. Abraham Brouwer at the Institute for Environmental Studies in Amsterdam, leading an EU project, concluded that organohalogens disturbed processing of retinoid-controlled pathways. The organohalogens cause a functional hyper-vitaminosis A with increased concentrations in plasma, liver and kidney, which can result in developmental abnormalities resembling the symptoms of excessive vitamin A intake.

Contaminants in baby foods: In baby food phthalat DBP and DEHP were found.They have endocrinous activities, hormone disruption.Milk used as ingredient for these products was the source of these plasticisers.(Bavaria, MUVA Kempten)

Use of Phthalates as Plasticiser:
Phthalates Abbreviation
   
Dietylhexylphthalate DEHP
Dibutylphthalate DBP
Diisodecylphthalate DIDP
Butylbenzylphthalate BBP
Bisphenol A BPA
Diisononyl phthalate DINP

In Western Europe, about one million tonnes of phthalates are produced each year, of which approximately 900,000 tonnes are used to plasticise PVC (polyvinyl chloride). All efforts should be made to reduce or even to avoid the possibility of contamination of the milk on its origin.


Plasticisers as possible cancer-causing agents

BPA is a synthetic resin used in food packaging and polycarbonate plastic products. and BBP is a widely used plasticiser used in food wraps and cosmetics. These compound can leach out of the plastic and migrate into the food when plastic is heated, old or scratched

According to Fox Chase Cancer Center in Philadelphia, BPA and BBP are environmental estrogens capable of affecting gene expression in the mammary glands of young female laboratory rats exposed to the compounds through their mothers milk. The changes of the gene expression profile of mammary tissue changes occording to the age. The decrease of the expression of the GADI gene is one of these changes. The GADI gene encodes a key enzyme of the GABA-ergic system, which could be involved in hormonal regulation and breast cancer development. GADI has consistently been overexpressed in primary breast cancer.

BBP exposure modifies the genomic expression of the mamary gland, more studies are therefore necessary to see wether these estrogens can lead to cancer and its implications to human kind.[2268].


Growth stimulating hormones in beef

Growth stimulating hormones and other chemicals are present in animal feed, beef and related products in Brazil and other developing countries. The most impportant are:

Dietylstilbestrol: It is a growth stimulating hormone.

Zeranol: (6-(6, 1C-dihydroxyundecyl) -resorcylic acid -2lactone) Non-hormonal anabolic agents for use as implants in several countries of the American continent. It is sold under the commercial brand-name of Ralgro.

Nortestosterone: Nortestosterone is a hormone that helps to increase protein synthesis, decrease protein breakdown, and increase workout intensity, increasing muscle size.

Trembolone: Trembolone acetate is a steroid having a short half life, probably no more than a day or two, though it is an extraordinarily potent AAS, being about three times as effective as testosterone esters.

Hexestrol: Is a diethylstilbestrol derivative having the uses of estrogen.

Dinestrol: It is an estrogen hormone.

Estradiol: Estradiol is the most active of the estrogens, the female sex hormones, and is responsible for the development of female sex organs and characteristics.

Testosterone: Testosterone is the most important representative of the male sex hormones collectively called androgens.

Medroxyprogesterone It is a growth stimulating hormone.

Salbutamol It is a beta sympathomimetics.

Clenbuterol It promotes muscle gains as well as fat loss and weight loss.

The BPA National Health and Nutrition Examination Survey (NHANES)

[2269]
According to Calafat and colleagfues 2008 BPA is used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP) . The authors measured the total urinary concentrations of BPA and tOP in the 2003-2004 National Health and Nutrition Examination Survey. BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively.

The authors concluded that urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. The study should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.

BPA: Bisphenol A (BPA; 2,2-bis(4-hydroxyphenyl)propane):
BPA is used in the manufacture of polycarbonate plastic and epoxy resins, which can be used in impact-resistant safety equipment and baby bottles, as protective coatings inside metal food containers, and as composites and sealants in dentistry. Exposure to BPA is thought to result primarily from ingestion of food containing BPA. [2270] [2271].

tOP: 4-tertiary-octylphenol (tOP; 4-(1,1,3,3-tetramethylbutyl)phenol):
tOP is both a degradation product of and an intermediate in the manufacture of octylphenol ethoxylates, which are nonionic surfactants used in detergents, pesticide formulations, and other applications. Exposure to tOP may occur from contact with personal care products, detergents, water, and food containing tOP.

BPA and tOP are of concern to environmental public health because of the high potential for exposure of humans to these phenols and their demonstrated animal toxicity.

Exposures to tOP can result in developmental and reproductive alterations in aquatic species and in laboratory animals. At high doses, BPA demonstrates estrogen-like effects on uterine and prostate organ weights in experimental animals. At doses below the putative lowest observed adverse effect level, exposure to BPA has reportedly resulted in decreased sperm production, increased prostate gland volume, altered development and tissue organization of the mammary gland, altered vaginal morphology and estrous cycles, disruption of sexual differentiation in the brain, and accelerated growth and puberty.

BPA in drinking bottles

[2272]
Hoa H. Le and colleagues evaluated the migratio of BPA into water stored in new or used high-quality polycarbonate bottles used by consumers. they found migration rates ranging from 0.20 ng/h to 0.79 ng/h. At room temperature the migration of BPA was independent of whether or not the bottle had been previously used. Exposure to boiling water (100$^{o}C$) increased the rate of BPA migration by up to 55-fold.

The authors concluded that the amounts of BPA found to migrate from polycarbonate drinking bottles should be considered as a contributing source to the total "EDC-burden" to which some individuals are exposed.

BPA and nonylphenol (NP) pollution a consequence of human domestic and industrial waste discharge

[2273]
Hodaka Kawahata and colleagues analyzed endocrine disrupters nonylphenol (NP) and bisphenol A (BPA) levels at various sites in Okinawa and Ishigaki Islands, Japan. River-water samples showed low to undetectable concentrations of NP and BPA, but appreciable amount of NP and BPA were detected in sediments at one coral reef site and in river sediment.

The authors stress that the influence of endocrine disrupters may have already begun on adjacent coral reefs and conclude that NP and BPA pollution is a consequence of human waste discharge, both domestic and industrial, and not by agricultural activities.

Sewage treatment plant effluents cannot be the only sources for tech.-4-NP found in the river water in Germany

[2274]
Four small freshwater streams in the region known as Hessisches Ried in Germany were investigated with respect to the temporal and spatial concentration variations of the endocrine disruptors bisphenol A (BPA), 4-tert-octylphenol (4-tert-OP), and the technical isomer mixture of 4-nonylphenol (tech.-4-NP).

Quednow and Püttmann 2007 found that BPA levels concentration were decreasing due to the European Directive 2003/53/EG which restricts the marketing and the use of nonylphenols [2275]. Results from the analysis of additionally collected water samples from sewage treatment plant effluents indicate that these efluents cannot be the only sources for tech.-4-NP found in the river water.

The European Directive 2003/53/EG [2275] aims to protect the environment and in particular the soil, when sewage sludge is used in agriculture, establishing a concentration limit value for NP and NPE in sewage sludge that is to be spread on land.

In order further to protect the environment, the placing on the market and the use of NP and NPE should be restricted for specific uses which result in discharges, emissions or losses to the environment.
Nonylphenol C6H4(OH)C9H19 and Nonylphenol ethoxylate (C2H4O)nC15H24O may not be placed on the market or used as a substance or constituent of preparations in concentrations equal or higher than 0,1 % by mass for the following purposes:

(1) industrial and institutional cleaning except:
- controlled closed dry cleaning systems where the washing liquid is recycled or incinerated,
- cleaning systems with special treatment where the washing liquid is recycled or incinerated;

(2) domestic cleaning;
(3) textiles and leather processing except:
- processing with no release into waste water, - systems with special treatment where the process water is pretreated to remove the organic fraction completely prior to biological waste water treatment (degreasing of sheepskin);

(4) emulsifier in agricultural teat dips;
(5) metal working except:
- uses in controlled closed systems where the washing liquid is recycled or incinerated;

(6) manufacturing of pulp and paper;
(7) cosmetic products;
(8) other personal care products except:- (9) spermicides; (10) co-formulants in pesticides and biocides.

Meat from USA and Australia with ractopamine refused by China:

Ractopamine is a beta-agonist like Clenbuterol. It is a feed additive to promote leanness in pigs raised for their meat.It was approved by the FDA in 1999 and also in countries like Australia, Brazil, Canada, Mexico, and Thailand. The EU did not approve it yet.

China refused 18 tons of US kidneys of pork, and 24 tons of Canadian cutlets because of traces of Ractopamine.

Only a trace amount of ractopamine need be added for a marked increase in protein and decrease in fat accretion in animals, in particular swine. For the last 90 pounds of live weight gain, a mere 18.5 grams of ractopamine added to a ton of feed (20 ppm) will increase protein by 24% and decrease fat by 34%. [2276]

When fed at the maximum rate (18g/ton), RAC can increase the amount of lean removed from the carcass from 51.8 to 57.5% (Schinckel et al., 2002). Schinckel found that ractopamine has a positive impact on barrows and gilts with substantially different genetic potentials for lean growth and carcass lean percentage, according to Schinkel. [2277]


International trade of Pesticides

The Rotterdam Convention on for Certain Hazardous Chemicals and Pesticides in International Trade text was agreed by governments in Rotterdam in September 1998. It requires 50 ratifications before it will come into force, and so far 20 governments have done so.

Growth in internationally traded chemicals during the 1960sand 1970s led to increasing concern over pesticides and industrial chemical use, particularly in developing countries that lacked the expertise or infrastructure to ensure their safe use. Therefore the following organisations were founded:

International Code of Conduct for the Distribution and Use of Pesticides by the Food and Agriculture Organisationn (FAO)

London Guidelines for the Exchange of Information on Chemicals in International Trade by the United Nations Environment Programme (UNEP).

Rotterdam Convention on the Prior Informed Consent (PIC) Procedure for Certain Hazardous Chemicals and Pesticides in International Trade September 1998.

The convention covers the export and import of hazardous chemicals and, by implication, their use and regulation.In both instances, less-advantaged importing countries often lack the means to manage hazards chemicals throughout their life cycle, from importation through use and safe disposal.
Many countries also face the problem of huge quantities of unused chemicals, dumped illegally or forgotten in unsafe storage areas, which can contaminate soil, water and air. Effective disposal systems for hazardous chemicals rarely exist. This was the case of the nitrofen scandal in animal feed in Germany where a warehouse, formerly used as nitrofen storage contaminated large quantities of feed grain.


List of the Rotterdam Convention on the Prior Informed Consent of banned or severely restricted chemicals

The list covers 29 of the most hazardous chemicals, most of them pesticides. The most important are:

Binapacryl: It is toxic to the liver, kidney and nervous system, especially among workers in hot environments. Can cause toxic psychosis and convulsions.

Ethylene dichloride: Effects range from liver and kidney damage to death from pulmonary oedema. Shown to cause stomach, lung, breast and other types of cancer in animals.

Ethylene oxide: Exposure results in respiratory tract irritation, sleeplessness, muscular weakness, diarrhoea, nausea, conjunctivitis and neurological disorders.

Toxaphene: Severe poisoning provokes convulsive seizures and coma. In some cases, it leads to hyperthemia, rapid heartbeat and death.

Granox TBC: In July 2000, sixteen farmers in Senegal died due to intoxication with Granox TBC and Spinox T, used to protect newly planted groundnut seeds against fungus and insects.

Spinox T
Parathion
Tetraethyl lead
Tetramethyl lead
Tributyltin oxide

Monocrotophos: It is an insecticide that is applied in many developing countries, particularly in Asia, to control insects and spider mites and weedkiller.

DNOC: It is a fungicide which is highly toxic to humans.

All forms of asbestos.


Annex III - Chemicals Subject To The Prior Informed Consent Procedure - Category Pesticide

2,4,5-T
Aldrin
Captafol
Chlordane
Chlordimeform
Chlorobenzilate
DDT
Dieldrin
Dinoseb and dinoseb salts
1,2-dibromoethane (EDB)
Fluoroacetamide
HCH (mixed isomers)
Heptachlor
Hexachlorobenzene
Lindane
Mercury compounds, Pesticide including inorganic mercury compounds, alkyl mercury compounds and alkyloxyalkyl and aryl mercury compounds
Pentachlorophenol.

Heptachlor in feed with fishmeal

[2278]
According to the EFSA Scientific Panel on Contaminants in the Food Chain heptachlor was commercially introduced as a non-systemic contact insecticide in 1945. It was also a major constituent (about 10%) of technical chlordane.

Heptachlor was used for agricultural purposes, soil and seed treatment, wood protection and termite- and household insect control. It has been banned for use in the European Union since 1984 and in most other countries worldwide because of the persistency in the environment of the two break-down products heptachlor epoxide and photoheptachlor.

All these compounds are lipophilic and particularly heptachlor epoxide and photoheptachlor tend to accumulate in the food chain.

Toxicity:

Heptachlor shows moderate acute toxicity and heptachlor epoxide and photoheptachlor are more toxic than heptachlor. In mammals, the main target organs are the nervous system and the liver, but also the reproductive and the immune system are affected. Heptachlor and heptachlor epoxide cause liver tumours in mice, but are not genotoxic.

Heptachlor is classified by IARC as possibly carcinogenic to humans (group 2B). Heptachlor is moderately or highly toxic to fish exposed via water, but no data from oral studies have been found.

Food chain:

Amongst the species studied, the domestic hen is the most sensitive species and egg production and hatchability are the critical endpoints. Total heptachlor (sum of heptachlor and heptachlor epoxide) is not frequently found in feed commodities. When present, it is mostly in fish derived products and only very infrequently in feed materials of plant origin. Heptachlor epoxide is the predominant contaminant.

Human exposure to heptachlor:

The present dietary exposure of the adult population to total heptachlor is below 1 ng/kg b.w. per day, which is two to three orders of magnitude below the tolerable daily intake of 0.0001 mg/kg b.w. as established by WHO in 2006.

Recommendations:

To reduce human exposure to heptachlor Scientific Panel on Contaminants in the Food Chain recommends to increase surveillance of feed:
- the Besides heptachlor and heptachlor epoxide, the analyses of feed samples, especially of marine origin, should also include the determination of photoheptachlor.
- In the clean-up of samples, treatment with sulfuric acid must be avoided in order to prevent the decomposition of the analytes.
- Inter-comparisons performed on biological samples revealed large discrepancies in the performance of laboratories, indicating scope for improvement of the analytical methods.
- Toxicity and kinetic studies in fish exposed to heptachlor and heptachlor epoxide via the diet are lacking and should be conducted.
- The Members States are requested by the Commission to report the results of their monitoring programmes on undesirable substances in animal feed.
- Special attention should be paid to the control of feed materials coming from areas of the world where heptachlor has recently been or still is used.

Category Severely hazardous

Methamidophos

Category Severely hazardous pesticide formulation

Monocrotophos
Phosphamidon
Methyl-parathion
Parathion

Category Industrial

Crocidolite
Polybrominated biphenyls (Hexa-, Deca-, Octa-)
Polychlorinated biphenyls (PCB)
Polychlorinated terphenyls (PCT)
Tris (2,3-dibromopropyl) phosphate

Non dioxin-like polychlorinated biphenyls (PCB) in feed and food

[2279] Polychlorinated biphenyls (PCB) cover a group of 209 different PCB congeners which can be divided into two groups according to their toxicological properties. One group, consisting of 12 congeners, show toxicological properties similar to dioxins, is therefore termed "dioxin-like PCB" (DL-PCB), and these have been included in the "Risk Assessment of Dioxins and Dioxin-Like PCBs in Food" performed by the EU Scientific Committee on Food (SCF). The other PCB, referred to as "non dioxin-like PCB" (NDL-PCB), have not been previously evaluated by the SCF or EFSA. Both groups of PCB, NDL-PCB as well DL-PCB, are usually found in feed and food.

PCB were widely used in a number of industrial and commercial applications. It is estimated that more than 1 million tons of technical PCB mixtures were produced world-wide since their first commercial use in the late 1920s. Although produced by comparable production processes, technical PCB mixtures contain both DL and NDL-PCB and may vary considerably with respect to their congener composition due to differences in the amount of chlorine and the reaction conditions applied.

Moreover, technical PCB mixtures contain other dioxin-like compounds as impurities, such as polychlorinated dibenzofurans (PCDF). The different compositions as well as the presence of toxicologically relevant impurities may have a significant impact on the results of toxicological studies with technical PCB mixtures.

Although the manufacture, processing and distribution of PCB has been prohibited in almost all industrial countries since the late 1980s, their entry into the environment still occurs, especially due to improper disposal practices or leaks in electrical equipment and hydraulic systems still in use. PCB are highly persistent and are globally circulated by atmospheric transport and thus are present in all environmental media.

Data on the occurrence of NDL-PCB in food and feed have been reported in different ways:
  1. as the sum of three PCB congeners (PCB 138, 153 and 180)
  2. as the sum of six PCB congeners (PCB 28, 52, 101, 138, 153, 180) often referred to as indicator PCB. The sum of these six indicator PCB represent 50% of total NDL-PCB in food, and is being used by the EU Scientific Committee on Food (SCF)
  3. as the sum of seven (sum of six indicator PCB plus PCB 118).
Accumulation of NDL-PCB and carry-over
Following exposure of farm animals, NDL-PCB will accumulate in meat, liver and particularly in fat tissues. PCB 138 and 153, both with six chlorine atoms, show the highest carry-over into milk and eggs, in the order of 50-60%. After cessation of exposure, levels in eggs and milk initially decrease rapidly to about 50%, followed by a slower elimination phase. In fattened animals like calves, piglets, and poultry, and also farmed fish, no steady state is obtained, due to the fact that these animals are slaughtered at a young age.

More than 90% of the NDL-PCB exposure in the general population is via food. Average daily dietary intakes of total NDL-PCB can be estimated to be in the range of 10-45 ng/kg body weight (b.w.) per day. Limited exposure data for young children, up to six years of age, indicates that the average intake (breastfeeding excluded) of total NDL-PCB is about 27-50 ng/kg b.w. per day. However, where data on both adults and children within a specific population were available, in general children had exposure levels 2.5 fold higher than adults. In specific subpopulations with high dietary PCB exposure such as Baltic Sea fishermen the daily intake from fish of the sum of the six NDL-PCB could be about 40 ng/kg b.w., corresponding to an intake of total NDL-PCB of 80 ng/kg b.w. per day before taking into account the rest of the diet. Breastfed infants are a group of high NDL-PCB intake which might be two orders of magnitude higher than adult exposure.

Other routes of exposure such as ambient and indoor air, dust and soil, do not usually contribute significantly to the body burden of the general population. However, there are situations in which contribution from contaminated indoor air could be considerable.

Technical PCB mixtures used in toxicity studies contain both NDL-PCB and dioxin-like compounds such as DL-PCB. These mixtures exert a variety of toxicological effects such as effects on liver, thyroid, immune function, reproduction and behaviour as well as carcinogenicity. The adverse effects reported in laboratory animals following exposure to individual NDL-PCB were effects on the thyroid, liver and brain biochemistry, as well as immunotoxicity, oestrogenicity, and reproductive and neurodevelopmental effects. The latter effects are particularly found in the offspring of rodents following in utero exposure. However, these effects are not all specific for NDL-PCB but are also to be seen following exposure to polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and DL-PCB.

Several NDL-PCB congeners are metabolised to hydroxy-PCB and/or methylsulfonyl-PCB. Some of these metabolites may contribute to hormone-like effects seen with PCB.

Results of in vitro and in vivo genotoxicity studies indicate that PCB are not mutagenic at the gene or chromosome level. Some NDL-PCB, in particular the lower chlorinated congeners, caused DNA damage, probably resulting from the formation of reactive oxygen species. In two-stage initiation-promotion studies, technical PCB mixtures containing NDL-PCB as well as DL-PCB promote liver carcinogenesis in rats, following initiation with genotoxic carcinogens. Data from animal experiments with several technical mixtures (Aroclor 1016, 1242, 1254 and 1260) indicate that PCB can cause liver and thyroid neoplasms in rats.

The International Agency for Research on Cancer (IARC) classified PCB in Group 2A (probably carcinogenic to humans), based on limited evidence in humans and sufficient evidence in animals. Evaluation of the cancer studies in rats with technical PCB mixtures, and comparison with data obtained with TCDD, indicate that the dioxin-like components in technical PCB mixtures are likely to be responsible for the carcinogenic response of these mixtures. No peer reviewed data are available on the carcinogenicity of individual NDL-PCB congeners.

Occupational exposures to PCB have been reported to be associated with an increased risk of cancer of the digestive system and possibly other sites. Some studies suggest that environmental PCB exposure may be linked to the development of breast cancer, although perhaps only in certain vulnerable sub-groups.

The most sensitive effects seen in studies with individual NDL-PCB congeners in experimental animals were liver and thyroid toxicity.

Considering that the "lowest observed adverse effect level" BB for the most sensitive effects (liver, thyroid) were 10 times higher than the NOAEL BB (400, 800, and 1,200 microg /kg b.w. for PCB 28, 128, and 153, respectively), the Panel chose an overall body burden of 500 microg /kg b.w. as a representative conservative body burden at the NOAEL (NOAEL BB) for all individual NDL-PCB and for the sum of NDL-PCB occurring in human tissues. Based on the median total concentration of all NDL-PCB measured in human milk sampled in European countries of about 240 nanog/g fat, and assuming 20% fat content in the human body, a median human body burden of about 50 µg/kg b.w. was estimated. Consequently the overall NOAEL MoBB is about 10.

During the nursing period, breastfed infants may have daily intakes, on a body weight basis, of NDL-PCB estimated to be about two orders of magnitude higher than the average adult intake. This elevated intake by the infants is related to the mother's long-term intake of NDL-PCB with food. However, the subtle neurodevelopmental effects that were reported in some studies of human infants were mainly associated with exposure to a mixture of NDL-PCB, DL-PCB, and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans, and any causal role of NDL-PCB is unclear. The Panel noted that in many other studies of infants, breastfeeding was associated with beneficial effects, in spite of the contaminants present in human milk.

Conclusion
In conclusion, no health based guidance value for humans can be established for NDL-PCB because simultaneous exposure to NDL-PCB and dioxin-like compounds hampers the interpretation of the results of the toxicological and epidemiological studies, and the database on effects of individual NDL-PCB congeners is rather limited.

There are however indications that subtle developmental effects, being caused by NDL-PCB, DL-PCB, or polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans alone, or in combination, may occur at maternal body burdens that are only slightly higher than those expected from the average daily intake in European countries.

Because some individuals and some European (sub)-populations may be exposed to considerably higher average intakes, a continued effort to lower the levels of NDL-PCB in food is warranted.
Dichlorovos [2280]
Dichlorvos is an organophosphate insecticide that acts by inhibiting acetylcholinesterase (AChE), which results in a disturbance of nerve signal transmission and induces rapid respiratory failure in most insects. The same mechanism is responsible for the acute toxicity in mammals, including humans. Dichlorvos is highly toxic by oral, dermal and inhalatory exposure (oral LD50 is 80 mg/kg b.w., dermal LD50 is 120 mg/kg b.w. and LC50 is 0.083 mg/l). It was also demonstrated to be a skin sensitizer.

The only use of dichlorvos supported by one applicant is against flower bulb pests during storage.

Dichlorvos has been evaluated for carcinogenicity in five long-term studies in mice and in six long-term studies in rats. The substance was administered orally via the diet in the drinking water or by gavage, or by inhalation (one study in rats).

Most of the studies provided no evidence for the induction of neoplasia and only in two gavage studies, one in F344/N rats and the other in B6C3F1 mice, was there some evidence for neoplastic responses. In these studies, increases in the incidence of mononuclear cell leukaemia in male rats, mammary fibroadenomas combined with adenomas in female rats, pancreatic acinar adenomas in male rats and forestomach tumours in male and female mice were reported. After considering all of the available data the PPR Panel concluded that with the exception of tumours of the forestomach in mice, there was no convincing evidence for a compound-related increase in tumour incidence. The response on mouse forestomach was a consequence of local, rather than systemic, exposure.

The PPR Panel concluded that the available data clearly demonstrate that dichlorvos is an in vitro mutagen, and that there is some limited evidence that dichlorvos is a site-of-contact in vivo mutagen but that the mechanism of this effect is unclear; the evidence for alkylation of DNA in vivo, a possible mechanism, is very weak.

The Panel was of the opinion that the weight of evidence suggests that this would not occur at the levels of exposure that would be encountered by the proposed use of the compound. In addition severe systemic toxicity would occur before any concentration in tissues other than in the forestomach is reached that would induce the tumourigenic effect.

Tryptophan and eosinophilia-myalgia-syndrome (EMS)

Tryptophan became popular in the 1970s as a safe, nonaddictive treatment for insomnia, premenstrual syndrome and depression. [2281]

Tryptophan had been produced for many years using non-genetically engineered bacteria convert nutrients into L-tryptophan. In the late 1980's the company Showa Denko decided to introduce a new, genetically engineered bacterium called Strain V.to accelerate and increase the efficiency of tryptophan production.

The product was released without primary tests and sold in 1988. It caused the deaths of 37 people and caused 1500 more to be permanently disabled. EMS is a debilitating disease characterized by severe muscle and joint pain, weakness, swelling of the arms and legs, fever, skin rash, and an increase of eosinophils in blood.

EBT (1-1-ethylidenebis tryptophan), was identified as a dimerization product of tryptophan. The high yields of tryptophan using the GM method made it possible for these compounds to react with themselves, generating the toxin. The activated charcoal used in filtering the tryptophan was reduced from 20 to 10 kilograms per batch to reduce costs. The desire to increase productivity and failing to comply with safety tests resulted in this catastrophe.

Studying samples of lots which caused the EMS epidemic outbreak in 1989 using RP-HPLC, six contaminant peaks were traced. Further contaminants could be classified as tryptophan metabolites, non-physiological oxidation compounds or carbonyl condensation compounds.

The authors stress the fact that knowledge of the identity and formation conditions of these contaminants may help to prevent their formation in a prospective manufacturing practice to comply strict demands on purity by licensing authorities and the etiologic agent of EMS is still not been identified beyond all shadow of doubt.

Simat and colleagues conclude that biotechnological processes require high purification process of the end-product because of side reactions of the fermentation. The purification process causes price difference between tryptophan for feed or for infusion quality. The purity criteria that must be complied with, set by the European Pharmacopoeia is 400 ppm of substances which are detected at 220 nm and includes all contaminants which might be responsible for EMS disease. [2282]

Chloropropanol in Soy sauce and vegetable hydrolyses.
Chloropropanols were found in surveys of acid hydrolysed vegetable protein (acid HVP) and some soy sauces and related products. The chloropropanols are 3-monochloropropane-1, 2-diol (3-MCPD) and 1, 3-dichloro-2-propanol (1, 3-DCP). Both are suspected carcinogens.

All sauces with high chloropropanols had been produced using an acid hydrolysis process. Soy sauces manufactured using only a traditional fermentation process did not give rise to the chloropropanols. It seems that acid hydrolysis was introduced to cut costs in the production of soy sauce, whereas the traditional process of fermentation was much expensive but the safe way.

3-MCPD (3-monochloropropane-1,2-diol) is a chemical which may be formed in foods by the reaction of chloride with lipids. It is the most commonly found member of a group of chemical contaminants known as chloropropanols. More recent evaluations by the European Commission's Scientific Committee on Food (SCF) and other expert committees have concluded that there is a lack of evidence of in vivo genotoxicity and proposed a provisional TDI level of 2 microg/kg body weight/day for the amount of 3-MCPD

Conotoxins [2283] A conotoxin, discovered in venom from the fish-eating cone snail Conus magus or magician's cone, made it possible to develop a pain treatment medicine, Prialt.

Cone shells are carnivorous; they eat other mollusks, worms, or fish. Cone shells are predominantly nocturnal, burrowing in the sand and coral during the daytime. The cone shells injects paralytic and lethal oligopeptide toxins in its preys,The venom mixture is specific to each cone shell species, containing 30-200 conotoxin peptides. According to Michael McIntosh, a new alpha conotoxin OmIA isolated from a cone snail species named Conus omaria was discovered. The conotoxin blocs nicotinic acetylcholine receptors. It activates production of the hormone dopamin which is deficient in Alzheimer patients. Conotoxins will be a useful tool in designing new medicines for a variety of brain disorders, including Alzheimer's and Parkinson's diseases, depression, nicotine addiction and perhaps schizophrenia.

Novel Class of Nicotinic Receptor Antagonists from snail Conus [2284]
The venoms of predatory marine snails (Conus spp.) contain diverse mixtures of peptide toxins with high potency and selectivity for a variety of voltage-gated and ligand-gated ion channels.

The authors describe the chemical and functional characterization of three novel conotoxins alfa D-VxXIIA, alfa D-VxXIIB, and alfa D-VxXIIC which are potent inhibitors of nicotinic acetylcholine receptors (nAChRs).

What to eat and drink in case of food poisoning
Food poisoning may be cause by chemicals (pesticides, heavy metals ...), bacteria (Salmonella, Shigella...)or their poisons (Staphylococcin...). Appropriate medication is necessary. See your doctor.
Mineral water cannot harm. Eat as little as possible. Take the food you have appetite for. Follow the diet given by your doctor.

Pyrrolizidine alkaloids as undesirable substances in animal feed

[2285]
The European Food Safety Authority released an opinion concerning pyrrolizidine alkaloids (PAs), a group of more than 350 individual compounds that share as a basic structure one of the four necine bases platynecine, retronecine, heliotridine, or otonecine. PAs are produced as secondary metabolites of more than 6000 plant species, belonging to the families of Boraginaceae, Compositae (Asteraceae) and Leguminosae (Fabaceae) and occur world-wide.

Basic alkaloids seem to accumulate in the seeds, whereas the respective N-oxides dominate in the green parts of a plant. In farm animals, however, acute intoxications caused by PAs are rare, as animals avoid PA containing plants if other feed is available. However, this recognition fails in preserved forages such as silage and hay.

PAs intoxication in animals:

Acute intoxications: hepatotoxicity and hemorrhagic liver necrosis. Long-term exposure: hepatic megalocytosis, veno-occlusion in liver and to a lesser extent in the lungs, proliferation of the biliary tract epithelium, fatty liver degeneration and liver cirrhosis.

PAs intoxication in humans:

In humans, PAs cause primarily hepatic veno-occlusive disease (VOD). Toxicological concerns about the potential human exposure to PAs were based on the results of extensive rodent studies indicating a carcinogenic potential of this class of compounds, and on the in vitro investigations that convincingly demonstrated that the dehydropyrrolic metabolites of PAs can form DNA-adducts, DNA-cross links and DNA-protein cross links, and result in genotoxicitiy and mutagenicity in a variety of bioassays conducted in rodent models.

PAs carry over in food:

PAs are excreted with milk of dairy cows (and lactating sheep) albeit at a low rate, varying between 0.04 and 0.08% of the ingested dose. Analyses in Australia indicated the presence of certain PAs in eggs. No residues have been found in other animal tissues. The contribution of the residues in animal derived tissues to human exposure is low; however, honey, in which PA residues are regularly found, deserves special attention.

Veterinary medicine residues in eggs and poultry meat


Nicarbazin in eggs

[2286]
According to a report from the UK Food Standards Agency into the possible causes of nicarbazin residues in chicken. Nicarbazin is a medicated feed additive used to treat a debilitating poultry disease called coccidiosis.

Nicarbazin is a coccidiostat used to treat a protozoan disease, coccidiosis, that can be debilitating or even fatal to poultry. It is used as a feed additive to control the disease at a critical period of the birds' lives but should not be used within five days of the birds' slaughter. This ensures no appreciable residues of it remain in chicken for human consumption. It is combined in equal amounts with another coccidiostat, narasin, in the only UK-licensed product that contains nicarbazin, Maxiban.

Residues can be found in poultry meat but are more common in poultry liver. Neither is a significant food safety risk at the levels found, but can be avoided with good farm practice. A UK action level for residues has been set at 200 $\mu$g/kg based on international Joint FAO/WHO Expert Committee on Food Additives (JECFA) considerations. Residues over 1000 $\mu$g/kg are investigated on-farm by Animal Health, as this amount suggests a possible failing in feed management. This recent investigation considered all detectable residues, including those below 200 $\mu$g/kg, which greatly increased the amount of data available to assess risk factors.

Nicarbazin application as an infertility agent

[2287]
Nicarbazin was tested in 2004 in field studies on its efficacy to support its registration by the Environmental Protection Agency (EPA) as a reproductive control agent for Canada geese. As a reproductive inhibitor for Canada geese in baits with contraceptive doses it reduces hatchability of eggs about 51 per cent. This is intended to reduce the population of at airports and resorts

Nicarbazin testing

[2288]
According to Andrew Cannavan and colleagues 1999 nicarbazin is a mixture of 4,6-dimethyl-2-hydroxypyrimidine (DMHP) and 4,4A-dinitrocarbanilide (DNC) It is licensed for use as a feed additive, at concentrations of 100-125 mg kg, in broiler chickens up to a maximum age of 28 days. The treatment must be withdrawn for at least 9 days prior to slaughter. Nicarbazin is not licensed for use in commercial egg-laying chickens in the UK, and consequently eggs should be free from nicarbazin residues. A joint FAO/ WHO Expert Committee recommended the use of DNC alone as the marker residue for nicarbazin, and fixed a maximum residue limit (MRL) of 200 mg kg21 in broiler chicken tissues.
Cross-contamination of feed of mill production lines can cause unwanted residues in eggs and broiler chickens.

The authors describe a method for the determination of nicarbazin in feeds using liquid chromatography-electrospray mass spectrometry (LC-ESI-MS).

Testing method of Eggs and meat

[2289]
Huet and colleagues 2005 write that accidental cross-contamination of feed can lead to residues of these compounds in eggs and/or muscle. They developed an ELISA method to screen for halofuginone and for dinitrocarbanilide (marker residue for nicarbazin) in eggs and meat.

Halofuginone hydrobromide in chicken and turkeys

[2290]
Halofuginone hydrobromide is a non-ionophoric plant-derived quinazolinone compound that is authorised as a coccidiostat feed additive for use in chickens for fattening, chickens reared for laying up to 16 weeks of age, and turkeys up to 12 weeks of age at a minimum-maximum concentration of 2-3 mg/kg in complete feed (Regulation (EC) No 2004/C 50/01). Despite the requirements set for feed business operators in Regulation (EC) No 183/2005, it is generally acknowledged that under practical conditions during the production of mixed feeds, a certain percentage of a feed batch remains in the production circuit and these residual amounts can contaminate the subsequent feed batches. This cross-contamination may result in the exposure of non-target animal species, and hence the potential health risks for non-target animal species as well as the potential residue deposition in foods derived from these non-target animal species have been evaluated.

Accidental ingestion of feed intended for chickens or turkeys containing halofuginone at the maximum authorised level of 3 mg/kg feed, could present a health risk for several non-target animal species, including rabbits, geese, partridges and quails, which might react with feed refusal and decreased body weight gain. This dose could also cause mortality in partridges.

The Panel on Contaminants in the Food Chain (CONTAM Panel) conclude that adverse health effects in non-target animals are unlikely to occur as a result of cross-contamination of feed up to a hypothetical level of 10% of the maximum authorised level of halofuginone in feed for target animals.

No kinetic or occurrence data were available to estimate the amount of halofuginone hydrobromide residues in milk, meat or offal from non-target animal species. Hence, consumer exposure was estimated using data from eggs and kinetic data from chickens for fattening at practical zero withdrawal time. The data were extrapolated to a concentration of 0.3 mg/kg feed to correspond to feed cross-contaminated with halofuginone at a level of 10% of the maximum authorised level. Using a food basket approach for foodstuffs of animal origin, the maximum human exposure level was estimated to be 0.1 $\mu$g/kg b.w. from eggs and 0.29 $\mu$g equivalents/kg b.w. for a 60 kg person) from liver, kidney, muscle and skin/fat.

Due to the unknown nature and toxicity of the residues in avian species, the CONTAM Panel could not reach conclusions on the potential impact for consumers of such exposure.

Bitter apricot kernel warning

[2291]
The German Federal Institute for Risk Assessment says that bitter apricot kernels can lead to poisoning. These kernels are being sold increasingly on the Internet. In some cases it is claimed that they can help to fight cancer.[2292] However, there is no scientific evidence to back this claim. [2293] [2294]

According to the German Federal Institute for Risk Assessment bitter apricot kernels have a high natural level of amygdalin. During digestion hydrocyanic acid is released from the glycoside which can lead to severe, acute poisoning. At high doses it can even prove fatal. Hence, bitter apricot kernels may involve health risks. Eating just a few kernels can already lead to the onset of acute poisoning symptoms. [2291]

Consumers should not, therefore, eat more than one or two bitter apricot kernels a day or even none at all for precautionary reasons. Unsubstantiated health claims, which could encourage desperate sick people to buy them, are irresponsible. [2291]

Amygdalin (called here vitamin B17)has been studied by FDA in USA and found useless to fight cancer. [2295]

The claim cancer cells have within them an enzyme which unlocks the poison in the amygdalin, and in this way the cancer cells are destroyed. Normal, healthy cells do not have this enzyme. Is not backed by any study. [2294]

Acute cyanide intoxications may arise from eating apricot kernels, choke cherries, and other stone fruit kernels with high concentrations of cyanogenic glycosides. Inadequately prepared cassava, when constituting the major part of the diet, may be hazardous. Amygdalin is also present in some sorts of cassava. [2295]

Fresh salat contaminated with poisonous groundsel

[2296]
The German Federal Institute for Risk Assessment (BFR) found flowers and leaves from the common groundsel (Senecio Vulgaris L) in fresh salad ready too eat mix of radicchio, frisee and lamb's lettuce.

Groundsel is a poisonous plant which recently grows together with radicchio and other lettuce types because some herbicides which control groundsel were prohibited. The plant produces senecionin and riddelin , which belong to the group of unsaturated pyrrolizidin alcaloids (PA). These alcaloids were found to be carcinogenic and mutagenic. Producer and consumer should wash carefully lettuce and discard all pieces of extraneous plants.
Photography of Senecio Vulgaris L.: http://wisplants.uwsp.edu/scripts/detail.asp?spcode=SENVUL

Nitrofurans in Shrimps from Bangladesh

[2297]
Import of frozen shrimp and fish from from Bangladesh are threatened because of high contents of nitrofurans . The EU introduced strict laws against the presence of nitrofurans in food and rejected food with nitrofurans above zero level. The United States admits hat is 0.3 parts per billion as permissible level for nitrofurans.

Imports of sea food may be stopped as the Bangladesh government does not pay attention to the matter. The problems with nitrofurans are known since 2005.

UK FSA response to nitrofurans in shrimps

[2298]
Test results have been received on warm water prawns and shrimps from SE Asia. The test results revealed that 16 out of the 77 samples of tested positive for illegal and unacceptable residues of nitrofuran drugs. These drugs are no longer permitted in the European Union for use in food producing animals. This is because of concerns including a possible increased risk of cancer in humans through long-term consumption.

The shrimps and prawns that were found to contain these residues are from Thailand, Vietnam, Indonesia, India and Bangladesh. Most of the samples with residues were tiger prawns and king prawns and not the cold water types which are used in the UK to make sandwiches and prawn cocktails. The affected batches are being recalled.

Illegal use of nitrofurans in Portugal

[2299] Although nitrofurans in food production are forbidden in the EU illegal use may still continue. According to a report from Antunes, Machado and Peixe 2006 indiscriminate use of nitrofurans might be implicated in the emergence in Portugal of two multiresistant Salmonella Typhimurium and of Salmonella Enteritidis in poultry industry. These bacteria presented a decreased susceptibility to nitrofurantoin.

Drugs contaminate US drinking weater from California to New York

[2300]
According to an investigation of Associated Press published by the Washington Post on March 10, 2008 pharmaceuticals such as antibiotics, anti-convulsants, mood stabilizers, acetaminophen Carbamazepine, Monensin (antibiotic administered to cattle), Sulfamethoxazole (antibiotic used in humans and animals), ibuprofen, chemotherapy drugs, and sex hormones (such as used in the anti-baby pill) are found in the US drinking water supplies.

Water authorities say that the water is safe because it is far below the levels of a medical dose. However, scientists are worried about long-term consequences to human health.

The article explains that pills and medicine taken all over the country is almost entirely eliminated by the body and is flushed down the toilet. Wastewater treatment does not eliminate these drugs and they are discharged into reservoirs, rivers or lakes and return as tap water.

According to Benjamin H. Grumbles, assistant administrator for water at the U.S. Environmental Protection Agency EPA recognizes this contamination as a growing concern.


Perfluorinated chemicals may reduce human fertility

[2301]
Fei, McLaughlin, Lipworth and Olsen found perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) to be hormonal disruptors. Both belong to the group of perfluorinated chemicals (PFCs), and are used in food packagings, such as grease-resistant packaging for microwave popcorn bags and pizza boxes, other applications are in the field of pesticides, clothing, carpets and personal care products, industrial surfactans emulsifiers and products like Teflon. PFOS may be concentrated in the food chain.

According to the study, women who had higher levels of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in their blood took longer to become pregnant than women with lower levels. If the findings of Fei and colleagues will be reproduced by other studies, the compound will have to be added to the list of risk factors for infertility.

The authors say that Men's sperm may also be affected by PFCs and contribute to the associations between PFC levels and time to pregnancy, however, however, data on PFC effects in fathers are not available yet.

The biological mechanisms by which exposure to PFOS and PFOA might reduce fertility are unknown, but interference in menstrual period indicate a possible pathway.

The authors concluded that exposure to PFOS and PFOA at levels plasma levels common in the general population in developed countries may reduce fecundity.

Data remain controversial

[2302]
Negri and colleagues, in a 2008 review found that research on health effects of perfluoroalkyl-compounds (PFOA) on possible endocrine disruption, thyroid and liver carcinogenicity, and development alteration remain controversial. Environmental Protection Agency (EPA) established in 2006 that every PFOA emission will be eliminated before 2015.

EFSA calls for more studies on PFOS and PFOA

[2303]
According to an opinion of the European Safety Agency in 2008, that fish seem to be an important source of human exposure to PFOS and also contribute to human exposure to PFOA. The agency, however, stresses that findings may be influenced by an over-representation of studies from polluted areas.

The Panel of the EFSA concluded that the general population in Europe is unlikely to suffer negative health effects from PFOS and PFOA, but high consumers of fish might slightly exceed the TDI for PFOS. The Panel called for further research on contamination of foods and feeding stuffs of these compounds.


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