Carcinogenicity studies testing protocols

U.S. EPA (1991) derived a cancer inhalation unit risk for sulfur mustard based on the results of inhalation animal studies conducted by McNamara et al. (1975, see Section 3.7.2) however, it was emphasized in the EPA report that the studies of McNamara et al. (1975) contained deficiencies which made a quantitative analysis difficult. Conducted in 1970, the studies do not conform to the modem norms of acceptable experimental protocol, and it is likely that there was bias in the assignment of the animals to the test categories (U.S. EPA, 1991). In addition, many of the exposures were very brief, included only a few animals, and many of the animals were sacrificed (and some were replaced) before their capacity to develop late-appearing tumors was fully developed (U.S. EPA, 1991). Despite these shortcomings, it was noted by EPA that the McNamara et al. data are the best available for estimating the carcinogenic potency of sulfur mustard. The authors of the EPA report analyzed two sets of McNamara s data one from a toxicity study and one from a carcinogenicity study (see Section 3.7.2). 

Phenol was tested for carcinogenicity by oral administration in rats in one study and in mice in one study. An increased incidence of leukaemia was reported in male rats treated with the lower dose but not in high-dose rats or in mice or female rats. Phenol was a promoter of mouse skin carcinogenesis in two-stage protocols. 

Cho SD, Kim JH, Kim DY, Lee Y, Kang KS (2003) Prevalidation study for OECD enhanced test guideline 407 protocol by gavage for 4 weeks using propylthiouracil and tamoxifen. Toxicol Lett 144 195-204 Clemmesen J, Hjalgrim-Jensen S (1978) Is phenobarbital carcinogenic A follow-up of 8078 epileptics. Ecotoxicol Environ Saf 1 567-70... 

Chronic exposure is needed to identify most carcinogens. The cancer bioassay is thus similar to the chronic toxicity test covered in the last chapter. The major difference is that the toxicologist and the pathologist are generally searching only for evidence of tumor formation, and certain of the clinical measurements typically associated with the chronic toxicity study may be omitted from the protocol. 

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