Teratogenicity mustard

Bone marrow toxicity is the major side effect of chlorambucil. Nausea is uncommon or mUd, and hair loss does not occur. Chlorambucil shares the immunosuppressive, teratogenic, and carcinogenic properties of the nitrogen mustards. 

Flales BF. 1982. Comparison of the mutagenicity and teratogenicity of cyclophosphamide and its active metabolites, 4-hydroxycyclophosphamide, phosphoramide mustard, and acrolein. Cancer Res 42 3016-3021. 

Mirkes PE, Fantel AG, Greenaway JC, et al. 1981. Teratogenicity of cyclophosphamide metabolites phosphoramide mustard, acrolein, and 4-ketochlorophosphamide in rat embryos cultured in vitro Toxicol Appl Pharmacol 58 322-330. 

Cyclophosphamide requires metabolic activation to form the teratogenic metabolites, phosphoramide mustard, and acrolein (Figure 34.5). The former metabolite produces single-stranded DNA breaks, DNA-DNA and DNA-protein crosslinking. In contrast, acrolein preferentially binds to proteins, and it concentrates in the... 

The subcommittee considered other possible studies, such as those of Hackett et al. (1987) and McNamara et al. (1975). The study by Hackett et al. (1987) was a teratology study in which rats and rabbits were intragastrically intubated with sulfur mustard. For rats, maternal toxicity and teratogenic effects were observed at all doses tested (0.5, 1.0, and 2.0 mg/kg per day) for rabbits, there was no evidence of teratogenic effects at any of the doses tested (0.4, 0.6, and 0.8 mg/kg per day) but maternal toxicity was observed at the two highest doses. Dosing lasted only a few days (10 days for rats or 14 days for rabbits) in the Hackett et al. (1987) study compared with the 21 weeks in the Sasser et al. (1989a) study. 

The long-term consequences from mustard gas exposure, particularly at low doses, are unknown. However, a one-time high-dose exposure can result in chronic and recurrent lung and eye problems. Mustard gas is also a known carcinogen, and can cause lung cancer later in life. The ability to cause birth defects in the children of exposed adults is not presently known however, it has the potential to be teratogenic. 

All vinca alkaloids are severe vesicants that can induce necrosis, cellulitis, and/or thrombophlebitis. Proper needle placement before administration should be assured to eliminate the risk of extravasation. Unlike the tissue damage caused by the vesicant action of nitrogen mustards and antibiotic antineoplastics, cold exacerbates tissue destruction. If extravasation occurs, apply heat for 1 hour fours time a day for 3 to 5 days, coupled with local hyaluronidase injections. Vinca alkaloids are all Category D teratogens and are fatal if administered by the intrathecal route. 

Danforth CH, Cater E (1954) Nitrogen mustard as a teratogenic agent in the mouse. Proc Soc Exp Biol Med 86 705-707. 

R. L. Rommereim and P. L. Hackett, Evaluation of the Teratogenic Potential of Orally-Administered Sulfur Mustard in Rats and Rabbits, Teratology, 1986,33, C70. 

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