Evaluation of the teratological and dominant lethal potential of N,N-bis-(2-hydroxyethyl)-p-phenylenediamine sulphate in a 6-month feeding study in rats.
N,N-Bis-(2-hydroxyethyl)-p-phenylenediamine sulphate (N,N-Bis) was administered to 40 male and 45 female Sprague-Dawley rats per group by admixture with their diets at levels of 0.03, 0.1 and 0.3% for periods up to 6 months. Methaemoglobin levels were determined at wk 6. After 90 days ten animals/sex/group were killed for studies of possible target organs, haematology and blood chemistry. After 90 days, 25 females in each group were mated to untreated males in a teratology study. At wk 20, 20 males in each group were transferred from the test diets containing N,N-Bis to the control diet and were mated to untreated females in a dominant lethal study. The remaining animals were killed after 6 months for terminal studies (gross examination of organs, haematology and blood chemistry). The males used in the dominant lethal study were also killed at month 6, to serve as a comparison recovery group (gross examination of organs). Feeding of N,N-Bis at levels up to 0.3% in the diet caused a significant reduction in the body weight of male rats. The only signs of gross pathology after either 3 or 6 months of N,N-Bis feeding were darkened thyroids. This effect was noted in the high-dose group at both time intervals and, to a lesser extent, in the mid-dose group at month 6, and it was also seen in most of the high-dose recovery males and in a small number of mid-dose recovery males. No pathological effects were detected microscopically after the feeding of N,N-Bis for 90 days. N,N-Bis was not teratogenic, nor did it induce a dominant lethal effect in this study when administered to rats at levels including those causing borderline toxicity.
D000818:Animals; D004032:Diet; D005260:Female; D005799:Genes, Dominant / Q000187:drug effects; D005804:Genes, Lethal / Q000187:drug effects; D006202:Hair Dyes / Q000633:toxicity*; D006203:Hair Preparations / Q000633:toxicity*; D008297:Male; D009153:Mutagens; D010655:Phenylenediamines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects; D013723:Teratogens; D013997:Time Factors
D006202:Hair Dyes; D006203:Hair Preparations; D009153:Mutagens; D010655:Phenylenediamines; D013723:Teratogens; C050768:N,N-bis-(2-hydroxyethyl)-4-phenylenediamine