Dieldrin carcinogenicity

In contrast to animal studies, epidemiological studies of workers employed in the manufacture of aldrin provide no conclusive evidence of carcinogenicity in humans. " One study of a cohort having mixed exposure to aldrin, dieldrin, and endrin found 9 deaths from cancer versus 12 expected. The workers had been exposed to the pesticides for a mean of 11 years and followed a mean of 24 years. A more recent examination of 2384 manufacturing workers, employed between 1952 and 1982, with exposure to a number of pesticides including aldrin found no excess mortality rates attributable to occupational exposures. Similarly, a 2 3-year follow-up of 570 aldrin- and dieldrin-exposed workers found no increase in overall mortality rates or mortality from liver cancer."... 

National Cancer Institute Bioassays of Aldrin and Dieldrin for possible Carcinogenicity. NCI Carcinogenesis Technical Report Series No 21, Washington, DC, DHEW Pub No (NIH) 78-821, 1978... 

Epidemiological studies examining cancer mortality in workers exposed to dieldrin showed no conclusive evidence of carcinogenicity in humans. A study of 870 men employed in the manufacture of aldrin, dieldrin, and endrin found no increase in mortality from all cancers there were apparent increases in mortality from cancers of the esophagus, rectum, and liver based on very small numbers. In another report, follow-up of 232 workers with similar exposures revealed 9 cancer deaths with 12 expected. Updated epidemiological studies of manufacturing workers have confirmed the earlier findings. A cohort... 

Accumulating evidence suggests that dieldrin is not a likely human carcinogen and that it acts as a species-specific hepatocar-cinogen in mice through nongenotoxic mechanisms. ... 

Aliphatic Epoxidation. Many aliphatic and alicylcic compounds containing unsaturated carbon atoms are thought to be metabolized to epoxide intermediates (Figure 7.4). In the case of aldrin the product, dieldrin, is an extremely stable epoxide and represents the principle residue found in animals exposed to aldrin. Epoxide formation in the case of aflatoxin is believed to be the final step in formation of the ultimate carcinogenic species and is, therefore, an activation reaction. 

Aldrin and endrin are listed as indefinite animal carcinogens dieldrin, as a known animal carcinogen (ref. 104). 

Long-term occupational exposure to fairly low levels of aldrin and dieldrin has not been documented to show any demonstrable adverse effects. Studies with animals fed dieldrin have shown that the liver can be damaged, and the immune system can be suppressed. Oral doses of aldrin and dieldrin have caused liver cancer in mice but not in rats. Data are inadequate to judge the carcinogenicity of aldrin and dieldrin in humans, but the USEPA considers them probable carcinogens based on sufficient evidence in animals. 

Dieldrin CNS effects (tremors convulsions, coma), nausea, vomiting Carcinogen (animal positive), liver damage (glycogen depletion, fatty infiltration, necrosis), kidney damage (fatty changes, necrosis)... 

The dangerous acute dose of the technical mixture has been estimated at about 30 g and the dangerous dose of lindane at about 7 to 15 g. However, as already mentioned, a single dose of 45 mg (or approximately 0.65 mg/kgD of lindane caused convulsions. Lindane shows a marked difference in toxicity to different species. Its toxic effect on laboratory animals compares favorably with that of DDT, but for several domestic animals, notably calves, lindane is more toxic than DDT or dieldrin. On a chronic systemic basis the a, p and y isomers are experimental carcinogens. Has been implicated in aplastic anemia. 

P-450s carry out aliphatic and aromatic hydroxylat-ions, aromatic epoxidations (leading to stable epoxides like dieldrin from aldrin, or arene oxides), 0-, N-, and S-dealkylations and oxidations, oxidative deaminations, and desulfurations among other reactions. Although the primary evolutionary role of the P-450 enzymes is to convert hydrophobic xenobiotics into more hydrophilic compounds and enhance their removal from the body, P-450s also catalyze reactions that lead to more reactive (and hence toxic) compounds. Several xenobiotics are converted into potential carcinogens via the cytochrome P-450 system. 

The perfect fit of Haber s rule to the carcinogenic action of dieldrin in mouse liver provided no evidence of a subthreshold dose. Therefore, nongenotoxic carcinogens should not be assumed to exhibit a threshold per se rather they must be evaluated with regard to mode of action and human relevance, as discussed in Chapter 13. 

In experiments on mice, aldrin and dieldrin showed a carcinogenic effect. Although no direct conclusion regarding the danger to human beings can be drawn from these experiments, their manufacture for crop protection purposes in the United States was prohibited from October 1974 by the Environmental Protection Agency. Maximum permissible residue values for dieldrin vary, in general, between 0 and 0.1 ppm. 

Heavily chlorinated hydrocarbon carcinogens such as dieldrin, DDT, and carbon tetrachloride are not positive in either the Ames test, the E. coli polA test, or yeast mitotic recombination assay. The reason for the lack of positive results for these compounds in all of the microbial assays is not known but may be related to their highly lipophilic nature which may result in their entrapment in microbial cell wall membranes. 

It is particularly true with respect to the assessment of carcinogenic risks that we have had to place virtually complete reliance upon extrapolation from animal tests. This has resulted in the restriction of use or removal from the marketplace of several chemical substances including pesticides - such as DDT, Aldrin, Dieldrin, Chlordane and Heptachlor. Other pesticides and chemicals already in use have also been found to be carcinogenic to one or more animal species in the National Cancer Institute testing program - now part of the National Toxicology Program. 

Hexachlorocyclopentadiene is the basis for a number of pesticides such as Chlorodane, Aldrin, Dieldrin, and Kepone. The production of some of these materials has been banned in many regions because of their carcinogenic properties and toxicity to wildlife. Hexachlorocyclopentadiene is also the raw material for chlorendic acid, which is used as a flame retardant (product information from Velsicol Chemical Corp.) for imsatimated polyester resins. 

Twelve different chemicals are commonly referred to as POPs, including aldrin, chlordane, dichlorodiphenyl-trichloro-ethene (DDT), dieldrin, endrin, heptachlor, hexachlorobenzene, mirex, PCBs, polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and toxaphene. Other POP chemicals are considered carcinogenic and include polycyclic aromatic hydrocarbons (PAHs), brominated flame retardants, as well as some organometallic compounds such as trib-utyltin. 

The lARC classified aldrin, dieldrin and endrin as Group 3 chemicals not classifiable as to their carcinogenicity to humans, but all the other chlorinated hydrocarbons (chlordane, heptachlor, mirex, toxaphene, hexachlorobenzene, pentachlorophenol and... 

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