VOL.: 26 (1981) (p. 115)
Chlorambucil can induce teratogenic effects in several animal species and embryolethality at doses nontoxic to the mother. It has been shown to induce mutations in bacteria and yeast, and chromosomal aberrations in human lymphocytes in culture.
The available data are not sufficient to evaluate the teratogenic or mutagenic potential or chromosomal effects of chlorambucil in humans.
Although no well-controlled epidemiological study of chlorambucil alone was available to the Working Group, several highly suggestive descriptive studies and numerous case reports point to the increased occurrence of acute nonlymphocytic leukaemia in patients treated with chlorambucil.
The experimental and clinical evidence taken together indicate that chlorambucil is very likely to be a human carcinogen.
N.B. - Since the meeting of the Working Group, the Secretariat became aware of a new epidemiological study, which documents an excess incidence of acute leukaemia in patients treated with chlorambucil (Berk et al., 1981). In a prospective, randomized clinical trial, 431 previously untreated patients with polycythemia vera were treated by phlebotomy alone, by phlebotomy plus chlorambucil or by phlebotomy plus radioactive phosphorus. The risk of acute leukaemia in patients given chlorambucil was 13 times that in patients treated by phlebotomy alone (p < 0.002). This study, in conjunction with the evaluation of the Working Group would provide sufficient evidence that chlorambucil is carcinogenic in humans.
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluation: Vol. 9 (1975)
Subsequent evaluation: Suppl. 7 (1987)
See Also: Toxicological Abbreviations