International Agency for Research on Cancer (IARC) - Summaries & Evaluations

(Group 2A)

For definition of Groups, see Preamble Evaluation.

VOL.: 54 (1992) (p. 213)

CAS No.: 64-67-5
Chem. Abstr. Name: Sulfuric acid, diethyl ester

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Diethyl sulfate is manufactured from ethylene and sulfuric acid. It is used principally as an intermediate (ethylating agent) in the manufacture of dyes, pigments and textile chemicals, and as a finishing agent in textile production. It is an obligatory intermediate in the indirect hydration (strong acid) process for the preparation of synthetic ethanol from ethylene.

No data were available on levels of occupational exposure to diethyl sulfate.

5.2 Human carcinogenicity data

One cohort study at a US isopropanol and ethanol manufacturing plant revealed an increased risk for laryngeal cancer. A subsequent case-control study nested in an expanded cohort at this plant indicated that the increased risk was related to exposure to sulfuric acid; the risk persisted even after exclusion of workers in the ethanol and isopropanol units. A cohort study from two US plants producing ethanol and isopropanol suggested an increased risk for cancers of the larynx, buccal cavity and pharynx, but not of the lung, in strong-acid workers. An association between estimated exposure to diethyl sulfate and risk for brain tumour was suggested in a study of workers at a US petrochemical plant.

No measurement of exposure diethyl sulfate was available for the industrial processes investigated in the epidemiological studies. It is therefore difficult to assess the contribution of diethyl sulfate to the increased cancer risks. Furthermore, exposure to mists and vapours from strong inorganic acids, primarily sulfuric acid, may play a role in increasing these risks.

5.3 Animal carcinogenicity data

Diethyl sulfate was tested for carcinogenicity by oral and subcutaneous administration in one strain of rats. After subcutaneous administration, a high incidence of malignant tumours occurred at the injection site. Following oral gavage of diethyl sulfate, forestomach tumours were observed. A low incidence of malignant tumours of the nervous system was observed in the same strain of rats after prenatal exposure.

5.4 Other relevant data

Diethyl sulfate induced specific locus mutations in mouse germ-line cells. It was clastogenic in mice and newts, induced DNA damage in mice and rats and ethylated DNA in mice. Diethyl sulfate induced chromosomal aberrations and micronucleus formation in cultured human lymphocytes. It induced alkali-labile sites in cultured human leukocytes in one study. In cultured mammalian cells, diethyl sulfate induced chromosomal aberrations, micronucleus formation, sister chromatid exchange, forward mutation and DNA single-strand breaks; it also induced unscheduled DNA synthesis in primary cultures of rat hepatocytes. In single studies, diethyl sulfate did not induce aneuploidy or reciprocal translocation in Drosophila melanogaster but did induce sex-linked recessive lethal mutations and genetic crossing-over. In plant cells, diethyl sulfate induced chromosomal aberrations, mutation and unscheduled DNA synthesis. It induced reverse mutation and mitotic recombination in yeast. Diethyl sulfate induced mutation and DNA damage in bacteria.

5.5 Evaluation

There is inadequate evidence for the carcinogenicity in humans of diethyl sulfate.

There is sufficient evidence for the carcinogenicity in experimental animals of diethyl sulfate.

Diethyl sulfate is a strong alkylating agent which ethylates DNA. As a result, it is genotoxic in virtually all test systems examined including induction of potent effects in somatic and germ cells of mammals exposed in vivo.

Overall evaluation

Diethyl sulfate is probably carcinogenic to humans (Group 2A).

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluations: Vol. 4 (1974) (p. 277); Suppl. 7 (1987) (p. 198)

Subsequent evaluation: Vol. 71 (1999)


Last updated: 13 April 1999

    See Also:
       Toxicological Abbreviations
       Diethyl sulfate (ICSC)
       Diethyl Sulfate  (IARC Summary & Evaluation, Volume 71, 1999)