For definition of Groups, see Preamble Evaluation.
VOL.: 50 (1990) (p. 169)
Chem. Abstr. Name: Acetamide, 2,2-dichloro-N-[2-hydroxy-1-(hydroxymethyl)-2-(4-nitrophenyl)ethyl]-[R-(R*,R*)]-
Chloramphenicol has been used widely as an antibiotic since the 1950s. Veterinary use of chloramphenicol has resulted in the occurrence of residues in animal-derived food.
No adequate study was available to evaluate the carcinogenicity of chloramphenicol to experimental animals.
Intraperitoneal administration of chloramphenicol to mice enhanced the incidence of lymphomas induced by 1,4-butanediol dimethanesulfonate.
Many case reports have described an unusual succession of leukaemia following chloramphenicol-induced aplastic anaemia and bone-marrow depression. Additional evidence for the association between use of chloramphenicol and leukaemia has come from a single large case-control study in China, which demonstrated a relationship with duration of exposure.
Use of chloramphenicol during the first trimester of pregnancy has not been associated with an increase in the incidence of congenital malformations. Chloramphenicol caused embryo- and fetolethality in mice, rats and rabbits.
In humans, chloramphenicol causes aplastic anaemia. In both humans and animals administered chloramphenicol, reversible suppression of the bone marrow is frequent whenever the drug reaches relatively high plasma concentrations.
Chloramphenicol induced chromosomal aberrations in bone-marrow cells of mice but not of rats treated in vivo. It induced chromosomal aberrations in meiotic cells of male mice. Contradictory results were obtained in dominant lethal tests in mice. In human cells, chloramphenicol did not induce sister chromatid exchange or chromosomal aberrations but gave contradictory results for DNA damage. It induced sister chromatid exchange in Syrian hamster cells. Chloramphenicol induced gene mutations in mouse lymphoma cells but did not induce DNA damage in hamster cells. Chloramphenicol did not induce sex-linked recessive lethal mutations in Drosophila. It induced chromosomal aberrations in plants. In haploid yeast, chloramphenicol induced petite mutations. In most studies, chloramphenicol was not mutagenic to and did not cause DNA damage in Salmonella typhimurium or Escherichia coli and did not induce DNA damage in Proteus mirabilis or Bacillus subtilis.
There is limited evidence for the carcinogenicity of chloramphenicol in humans.
There is inadequate evidence for the carcinogenicity of chloramphenicol in experimental animals.
In making the overall evaluation, the Working Group also took note of the following information. Chloramphenicol induces aplastic anaemia, and this condition is related to the occurrence of leukaemia.
Chloramphenicol is probably carcinogenic to humans (Group 2A).
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol. 10 (1976) (p. 85); Suppl. 7 (1987) (p. 145)
Last updated: 11 November 1997
See Also: Toxicological Abbreviations Chloramphenicol (WHO Food Additives Series 53) Chloramphenicol (WHO Food Additives Series 23) Chloramphenicol (WHO Food Additives Series 33) CHLORAMPHENICOL (JECFA Evaluation)