Epichlorohydrin, carcinogenicity

Ammonia. l-Chloro-2,3-epoxypropane (epichlorohydrin). Carcinogenicity of cadmium and its compounds. 

Some laboratory studies with rats and mice have linked trichloroethylene exposure to various types of cancers. Several of these studies, however, should be viewed cautiously, since the tumorigenic activity might be influenced by the presence of direct-acting compounds, namely the epoxides (e.g., epichlorohydrin) added as stabilizers in trichloroethylene. Epoxides are known to be very reactive, and some, such as epichlorohydrin, are potent carcinogens themselves. 

Toxicology. Epichlorohydrin is a severe irritant of skin, eye, and respiratory tract. Repeated or prolonged exposure can cause lung liver and kidney damage. It is a direct-acting mutagen and is carcinogenic in experimental animals. 

The carcinogenic risk to humans cannot be fully assessed, however, because of mixed exposures, limited number of deaths, and indeterminate levels and duration of exposure. The lARC has determined that there is sufficient evidence of carcinogenicity in animals and inadequate evidence in humans and that epichlorohydrin is probably carcinogenic to humans. ... 

The proposed 2003 ACGIH threshold limit value-time-weighted average (TLV-TWA) for epichlorohydrin is 0.1 ppm (0.38mg/m ) with an A2-suspected human carcinogen designation and a notation for skin absorption. 

Wester PW et al Carcinogenicity study with epichlorohydrin (CEP) by gavage in rats. Toxicology 36 325-339, 1985... 

Laskin S, Sellakumar AR, Kuschner M, et al Inhalation carcinogenicity of epichlorohydrin in noninbred Sprague-Dawley rats. J Natl Cancer Inst 65 7 51-757, 1980... 

Epichlorohydrin was tested for carcinogenicity in mice by subcutaneous injection it produced local sarcomas. It was active as an initiator in a two-stage carcinogenesis study in mice (lARC, 1976). 

There is inadequate evidence in humans for the carcinogenicity of epichlorohydrin. 

Laskin, S., Sellakumar. A.R., Kuschner, M., Nelson. N., La Mendola, S., Rusch, G.M., Katz, G.V., Dulak, N.C. Albert, R.E. (1980) Inhalation carcinogenicity of epichlorohydrin in non-inbred Sprague-Dawley rats.natl Cancer Inst., 65, 751-757... 

Sram, R.J., Tomatis, L., Clemmesen, J. Bridges, B.A. (1981) An evaluation of the genetic toxicity of epichlorohydrin. A report of an expert group of the International Commission for Protection against Environmental Mutagens and Carcinogens. Mutat. Res., 87, 299-319... 

Based on animal studies and mutagenicity studies, trace amounts of organic polymers do not appear to present a toxicity problem in drinking water. The reaction products with both chlorine and ozone also appear to have low toxicity. The principal concern is the presence of unreuctcd monomer and other toxic and potentially carcinogenic nonpolymeric organic compounds in commercial polymeric flocculants. The principal contpuimds are acrylamide in acrylamide based polymers, dimethyldiallyammonium chloride in allylie polymers, and epichlorohydrin and chlorinated propanols in polyamines, as well as the rcaclion products of these compounds with ozone and chlorine. 

Sultaines are made by condensing propane sultone with a tertiary amine. These products are relatively rare in industry. Propane sultone is a known human carcinogen, so it must be handled with great care and thus the cost of these products is fairly high. The properties are similar to those of hydroxysultaines which are made by condensing epichlorohydrin with sodium bisulfite to make a propanechlorohydrin sulfonate which is then reacted with a tertiary amine to make a hydroxysultaine with sodium chloride as a by-product (see Figure 6.16). 

Older epoxy resins were noticed to cause skin cancer in laboratory animals. This was most likely due to the epichlorohydrin. Most newer epoxy resins, which contain less epichlorohydrin, do not seem to cause cancer in animals. Certain curing agents, such as metaphenylene diamine (MPDA) and diaminodiphenyl sulfone (DADPS), and certain gly-cidyl ethers are carcinogenic in laboratory animals. It is not known if these materials cause cancer in humans. 

There is sufficient evidence in experimental animals for the carcinogenicity and teratogenicity of epichlorohydrin exposure via oral and inhalation routes. Epichlorohydrin was tumorgenic in rats exposed (inhalation) to concentrations as low as 100 ppm per 6 h day over 30 days. 

Epichlorohydrin has been shown to cause chromosomal aberrations in humans, and is classified as a probable human carcinogen (group 2A). 

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