Toxicity 90-day study

Subchronic Dermal Toxicity 90-Day Study (Original Guideline, adopted 12 May 1981)... 

OECD, 1981c, Test Guideline 412, Repeated Dose Inhalation Toxicity 28-Day or 14-Day Study. OECD, 1981d, Test Guideline 413, Subchronic Inhalation Toxicity 90-Day Study. 

The committee concluded that the best evaluation for this purpose was a 90-day study in rats. An ADI of 0 to 2 mg/kg body weight was allocated based on a NOEL of 200 mg/kg body weight per day (the highest dose tested in the study) and a safety factor of 100. Although the ADI was based on the results of a shortterm study, the supporting data and lack of effects at much higher doses in some studies (e.g., a study of developmental toxicity) indicated that the safety factor of 100 was appropriate. 

In a 90-day toxicity study in which 179 mice received diisopropyl methylphosphonate in the diet at doses of 0, 27, 91, or 273 mg/kg/day, two deaths occurred in the 91 mg/kg/day male group. Since no deaths were observed in the 273-mg/kg/day group and no other signs of toxicity were observed, it was concluded that there was no evidence of toxicity in this 90-day study (Hart 1976). Four male rats died (1 control, 1 low-dose, and 2 high-dose animals) out of a total of 256 animals in a 90-day study, in which rats received diisopropyl methylphosphonate in the diet at doses of 0, 30, 100, or 300 mg/kg/day. The deaths were neither dose nor duration related and were not considered of toxicologic importance (Hart 1976). 

One of the toxic effects the chronic study is designed to detect is cancer formation. Some toxicologists believe, in fact, that cancer is the only form of toxicity not detectable in 90-day studies Indeed, it is difficult to find many examples of forms of toxicity occurring in chronic studies that were not detectable, at higher doses, in 90-day studies. It appears that, in most cases, the chronic exposure allows the effects that were detected in 90-day studies to be detected at lower doses, but does not reveal new forms of toxicity, except possibly cancer. This is not a sufficiently well-established generalization to support rejection of the need for chronic studies, and, of course, the toxicologist obviously needs to determine whether a chemical can increase the rate of tumor formation. So chronic studies will be around for some time. 

Reproductive Toxicity. No studies were foimd regarding reproductive toxicity of 3,3 -dichloro-benzidine. Should data suggesting that reproductive organs are affected in a 90-day study become available, multigenerational reproductive studies in animals may be warranted. 

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