For definition of Groups, see Preamble Evaluation.
VOL.: 63 (1995) (p. 245)
CAS No.:
Chem. Abstr. Name: Trichloroacetaldehyde
5.1 Exposure data
Chloral has been produced commercially since the 1940s by chlorination of ethanol. Until the early 1970s, its major use was in the production of the insecticide DDT. Chloral is also used as an intermediate in the production of the insecticides methoxychlor, naled, trichlorfon and dichlorvos, the herbicide trichloroacetic acid and the hypnotic drugs chloral hydrate, chloral betaine, -chloralose and triclofos sodium.
Human exposure to chloral (or its hydrate) can occur during its production and use, from drinking chlorinated water and from pharmaceutical use.
Chloral is rapidly converted to its hydrate in contact with aqueous solutions.
5.2 Human carcinogenicity data
No data were available to the Working Group.
5.3 Animal carcinogenicity data
Chloral hydrate was tested for carcinogenicity in one adequate study in male mice by oral administration. It increased the incidence of hepatocellular adenomas and carcinomas.
5.4 Other relevant data
Chloral hydrate is metabolized rapidly in both humans and experimental animals to trichloroethanol and trichloroacetate. Its main acute toxic effects in humans are inhibition of respiration and induction of cardiac arrhythmia. Repeated administration of chloral hydrate damages the liver in mice and in male rats. Exposure of mice by inhalation results in damage to Clara cells in the lung.
Chloral hydrate crosses the human placenta, but there have been no reports of adverse results other than an increased likelihood of hyperbilirubinaemia in infants. No malformations and no effect on development were observed in the offspring of mice administered chloral throughout gestation.
Chloral hydrate is a well-established aneuploidogenic agent. It clearly induced aneuploidy and micronuclei in mammals treated in vivo, whereas chromosomal aberrations were not found in most studies. Conflicting results were obtained with regard to the induction of DNA damage in mammals treated with chloral hydrate in vivo.
Chloral hydrate induced aneuploidy and micronuclei in cultured human cells in vitro, but the results with regard to the induction of sister chromatid exchange were inconclusive. In rodent cells in vitro, chloral hydrate increased the induction of micronuclei but did not induce DNA damage; chromosomal aberrations were induced in a single study in vitro. In fungi, chloral hydrate clearly induced aneuploidy, while the results of studies on mitotic recombination and gene conversion were inconclusive. A single study showed induction of somatic mutation by chloral hydrate in insects. The results of assays for mutagenicity in bacteria were inconsistent.
5.5 Evaluation
There is inadequate evidence in humans for the carcinogenicity of chloral and chloral hydrate.
There is inadequate evidence in experimental animals for the carcinogenicity of chloral.
There is limited evidence in experimental animals for the carcinogenicity of chloral hydrate.
Overall evaluation
Chloral and chloral hydrate are not classifiable as to their carcinogenicity to humans (Group 3).
For definition of the italicized terms, see Preamble Evaluation.
Synonyms for chloral
Last Updated 05/22/97
See Also:
Toxicological Abbreviations
Chloral and chloral hydrate (IARC Summary & Evaluation, Volume 84, 2004)