Reproductive effects of inhaled XXXX in the male Fischer 344 @entity35 . I. Mating performance and dominant lethal assay.

@entity4199 @entity19 @entity4198 @entity1358 @entity35 @entity4201 @entity204 @entity4200
@entity4198 ( @entity4199 ) is a direct-acting mutagen in bacteria, induces @entity1358 in male @entity19 , and is a potent reproductive toxicant in the male Fischer 344 (F-344) @entity35 . A dominant lethal assay was performed to examine the possibility that @entity4199 may be a germ cell mutagen in the F-344 male @entity35 . Groups of 40 @entity35 each were exposed to 0, 1000, or 3000 ppm @entity4199 6 hr/day for 5 consecutive days, or received a single ip injection of 0.2 mg @entity4200 ( @entity4201 )/kg as a positive control. Each male was bred to a single female weekly for 8 weeks, and the standard criteria of dominant lethal tests were recorded. Exposure to 1000 ppm @entity4199 caused no consistent change in any parameter relative to control values. TEM caused increases in pre- and postimplantation loss indices in Weeks 1 to 5 postexposure, corresponding to sperm exposed in the epididymis and as early to late stage spermatids in the testis. Exposure to 3000 ppm @entity4199 caused a slight increase in postimplantation loss at Week 1 postexposure only, i.e., in sperm exposed in the epididymis or vas deferens, and increases in preimplantation loss throughout the 8 weeks postexposure. Fertility of the 3000 ppm @entity4199 -exposed males was significantly decreased by Week 2 after exposure, and never recovered to control values during the period of observation. It is suggested that the increased preimplantation losses are due, at least in part, to cytotoxic rather than genotoxic effects. High concentrations of inhaled @entity4199 , however, do induce dominant lethal mutations (reflected as an increased level of postimplantation fetal @entity204 ) in sperm located within the vas deferens and epididymis at the time of exposure.
