Repeated-Dose Dermal Toxicity Test 21- and 28-Day Study

Repeated-Dose Dermal Toxicity Test (21- and 28-Day Study) 

Test System The adult rat, rabbit, or guinea pig have been considered useful for repeated dermal toxicity studies. Other species may be used if justified. The body weight for different species should range as follows rats 200 to 300 g rabbits 2 to 3 kg guinea pig 350 to 450 gm. 

At least 10 animals (5 male, 5 female) with healthy skin should be used at each dose level. Females should be nulliparous and nonpregnant. If interim sampling or sacrifices are planned, the number should be increased by the number scheduled 

The dose levels for repeated dermal toxicity studies in animals should have at least three concentrations, including an appropriate vehicle control. Except for treatment with the test chemical, the control group should be handled in a manner identical to the test group. The highest-dose level should not produce evidence of toxicity attributable to the test chemical. 

Where there is usable estimation of human exposure, the lowest level should exceed this. Ideally, the intermediate-dose level(s) should produce minimal observable toxic effects. If more than one intermediate dose is used, the dose levels should be spaced to produce gradation of toxic effects. In the low and intermediate groups and in the controls, the incidence of fatalities should be low to permit a meaningful evaluation of the results. If application of the test chemical produces severe irritation, the concentration may be reduced. This reduction may result in a subsequent reduction in, or absence of, other toxic effects observed at the high-dose level. If the skin shows severe damage, it may be necessary to terminate the study and undertake a new study at lower concentrations. 

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