Mirex carcinogenicity

Carlson J, Abraham R. 1985. Nuclear ploidy of neonatal rat livers Effects of two hepatic carcinogens (mirex and dimethylnitrosamine). J Toxicol Environ Health 15(5) 551-559. 

Mirex has caused liver tumors in mice and rats and must be considered a potential human carcinogen (Waters et al. 1977 NAS 1978). Long-term feeding of 50 and 100 mg mirex/kg ration to rats of both sexes was associated with liver lesions that included neoplastic nodules and hepatocellular carcinomas neither sign was found in controls (Ulland et al. 1977). 

Ulland, B.M., N.P. Page, R.A. Squire, E.K. Weisburger, and R.L. Cypher. 1977. A carcinogenicity assay of mirex in Charles River CD rats. J. Natl. Cancer Inst. 58 133-140. 

We do not know for sure whether either mirex or chlordecone causes cancer in humans. The Department of Health and Human Services (DHHS) has determined that mirex and chlordecone may reasonably be expected to be carcinogens. The International Agency for Research on Cancer (IARC) has determined that mirex and chlordecone are possibly carcinogenic to humans. The EPA has not classified mirex or chlordecone as to carcinogenicity. In rodents, mirex causes liver, adrenal, and blood cancer. Chlordecone also causes liver cancer in rodents, but because of problems with these animal studies, more information is necessary to be sure. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of mirex and chlordecone are indicated in Tables 2-1 and 2-2 and Figures 2-1 and 2-2. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for mirex and chlordecone. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

In its evaluations, the DHHS has determined that both mirex and chlordecone may reasonably be anticipated to be carcinogenic on the basis of sufficient evidence of carcinogenicity in animals (NTP 1994). However, neither mirex nor chlordecone has been classified by the EPA with regard to cancer inducing potential (EPA 1994). 

Cancer. No studies have been conducted in human populations to determine whether mirex or chlordecone causes cancer. However, studies in mice and rats have demonstrated the ability of mirex to cause liver tumors (Innes et al. 1969 NTP 1990 Ulland et al. 1977a), pheochromocytomas (NTP 1990), and rare renal tumors (NTP 1990). A study in mice and rats also showed the ability of chlordecone to increase liver tumors (NC11976). As indicated above, available data on the genotoxicity of mirex and chlordecone indicate that these chemicals do not cause cancer by a mutagenic mechanism but rather by tumor promotion. Both mirex and chlordecone are considered by the DHHS to be substances that may reasonably be anticipated to be carcinogens and by IARC to be possible human carcinogens. EPA has not classified mirex or chlordecone as to their carcinogenicity. 

No evidence for carcinogenicity in exposed humans was found in the available literature. Animal studies provide sufficient evidence that mirex and chlordecone are carcinogenic after oral exposure... 

DHHS. 1991. Mirex Chlordecone Sixth Annual Report on Carcinogens. Summary 1991. ppg 238-240, 261-262. U.S. Department of Health and Human Services, Public Health Service. 

IARC. 1979c. Mirex. IARC Monographs on the evaluation of carcinogenic risk of chemicals to humans. Lyon, France World Health Organization, International Agency for Research on Cancer 20 283- 301. 

There are no reports of chronic toxicity in humans with mirex exposure. On the basis of findings in animal studies, mirex should be considered a potential carcinogen for humans. 

Highly toxic by oral, dermal, and possibly other routes of exposure toxic properties similar to those of Mirex however, more toxic than the latter symptoms include tremors, ataxia, hyperactivity, muscle spasms, and skin changes highly injurious to liver, kidney, and central nervous system a teratogenic substance caused testicular atrophy, sterility, low sperm count, and breast enlargement in experimental animals sufficient evidence of carcinogenicity in experimental animal also, possibly carcinogenic to humans. (lARC... 

Mirex has caused liver tumors in mice and rats and must be considered a potential human carcinogen. Long-term feeding of 50.0 and... 

Mirex is classified as a Group 2B carcinogen, indicating that it is a possible human carcinogen. For the protection of human health, oral intake should not exceed 0.0002 mg/kg... 

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... 

Enzyme induction is an increase in enzyme activity as a result of increased concentration of enzyme protein. Hundreds of chemicals have been shown to induce CYP450 and other enzymes. Most of these are Upophiles. These include pharmaceuticals, hormones, organochlorine pesticides, PAHs, including PCBs, and other carcinogenic species [3]. Some pesticides and their decomposition products are powerful inducers. Mirex induces at levels as low as 1 mg/kg. TCDD induces at a level of 1 ig/kg in some animal species. 

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