© 1993 Oxford University Press
research-article |
The Effects of Prenatal Administration of Azo Dyes on Testicular Development in the Mouse: A Structure Activity Profile of Dyes Derived from Benzidine, Dimethylbenzidine, or Dimethoxybenzidine1
Developmental Reproductive Biology Section, RTB, DTD, USEPA MD-72, Research Triangle Park, North Carolina 27711
Received June 22, 1992; accepted October 16, 1992
In mice and rats, prenatal exposure to the dye Congo red permanently reduces the number of germ cells in male and female offspring. In the current investigation, nine other dyes structurally related to Congo red were examined for developmental testicular toxicity. In this study, the structural component of the dyes responsible for the prenatal induction of germ cell aplasia was identified. We found that only benzidine-based dyes altered testicular development and caused hypospermatogenesis in mice during adulthood. Dimethyl-and dimethoxybenzidine-based dyes were without effect. Pregnant mice were dosed orally on Days 8–12 of gestation with a benzidine-, dimethlybenzidine-, or a dimethoxybenzidine-based dye and the testes of 45- to 50-day-old male offspring were examined. The testes of postpubertal male offspring exposed to the benzidine-based dyes, Congo red, diamine blue, and Chlorazol Black E, were small and contained some tubules completely devoid of germ cells, but the dimethlybenzidine-based dyes, trypan blue, Evans blue, and benzopurpurin 4B, and the dimethoxybenzidine-based dye, Chicago sky blue, did not alter testicular development in this manner. Azoic diazo component 48, a dimeth-oxybenzidine congener, and two other diazo dyes, naphthol blue black and Sudan III, were also without effect on the germ cells. Experiments with Chlorazol Black E (CBE) indicate that the period of susceptibility in the male fetus is limited to the period of primordial germ cell migration and division. When CBE was administered on Days 8–10 of gestation it reduced testis weight after puberty by 30%, while treatment after Day 13 did not affect testicular function. It is interesting to note that the structure—activity relationship of the dyes for developmental toxicity following oral administration differs considerably from that produced by maternal ip administration.