Carcinogenic alkylating agents

Alkylation Hazards arise from the alkylating agents, e.g. dimethyl sulphate (suspected human carcinogen), hydrogen fluoride (highly toxic irritant gas) Thermal alkylation processes require higher temperatures and pressures, with associated problems... 

As alkylating agent an alkyl halide, alkyl tosylate or dialkyl sulfate is used in most cases the latter type of reagent is often used in the preparation of methyl and ethyl ethers by employing dimethyl sulfate and diethyl sulfate respectively. Dimethyl sulfate is an excellent methylating agent, but is acutely toxic as well as carcinogenic." ... 

There is much evidence to suggest that carcinogenic N-nitros-amines are metabolised by an oxidative process to produce an alkylating agent (J f2) One potential metabolite is therefore the corresponding N-nitrosamide resulting from 2-electron oxidation at the oc-carbon atom, and, indeed, such compounds appear to induce tumours at the site of application without metabolic activation (3) It follows that the chemical properties of N-nitrosamides are relevant to the etiology of cancer ... 

N-nitroso compounds, once formed and present in vivo> generally do not revert easily or readily back to precursors. Instead, in vivo> they are metabolized or otherwise converted to alkylating agents as terminal or proximal carcinogens. 

HD is a vesicant (blister agent) and alkylating agent producing cytotoxic action on the hematopoietic (blood-forming) tissues which are especially sensitive. The rate of detoxification of HD in the body is very slow, and repeated exposures produce a cumulative effect. It causes blisters, irritates the eyes, and it is toxic when inhaled. HD has been determined to be a human carcinogen by the International Agency for Research on Cancer. 

Administered by gavage for 1.5 years, allyl chloride was not carcinogenic to rats but caused a low incidence of squamous cell carcinomas of the forestomach in mice. It is geno-toxic in a number of in vitro assays and is a direct alkylating agent." The lARC has determined that there is inadequate evidence in experimental animals for the carcinogenicity of allyl chloride and that it is not classifiable as to its carcinogenicity to humans. ... 

Preussman R Direct alkylating agents as carcinogens. Food Cosmet Toxicol6-.516-Sn, 1968... 

Dimethyl carbamoyl chloride is a direct-acting alkylating agent with a wide spectrum of genotoxic activity." ACGIH has classified dimethyl carbamoyl as A2-a suspected human carcinogen with no threshold limit value (TLV). 

Van Duuren BL, Goldschmidt BM, Katz C, et al Carcinogenic activity of alkylating agents. 7 Natl Cancer Inst Sh-.695-1QQ, 1974... 

BPL is a direct-acting alkylating agent and forms DNA adducts. It is mutagenic in a wide variety of in vitro and in vivo systems, both in somatic and germ cells. The lARC has determined that BPL is carcinogenic in experimental animals and that it is possibly carcinogenic to humans. ... 

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