Comparison of the dominant lethal effects of acrylonitrile and acrylamide in male Fischer 344 rats

Acrylonitrile (ACN) and acrylamide (AA), structurally similarvinyl monomers, are both animal carcinogens. ACN is weakly mutagenicin bacteria and induces sister-chromatid exchange, unscheduledDNA synthesis and cell transformation in cells in culture. AAinduces chromosomal aberrations in bone marrow, blood and germcells in vivo, and dominant lethal mutations in the germ cellsof male mice and rats. In the current study, the ability ofAA and ACN to induce dominant lethal mutations in the germ cellsof male Fischer 344 rats was compared. Three groups of 50 maleswere gavaged daily for 5 days with ACN (60 mg/kg in normal saline),AA (30 mg/kg in normal saline) or vehicle only; an additionalgroup of 20 males received a single i.p. injection of 0.2 mg/kgtriethylenemelamine (TEM) on the afternoon of day 5. Starting1 day after exposure, each male was bred to one female per weekfor 4 weeks (TEM-exposed group) or 10 weeks (ACN, AA and controlgroups). Mating rates were reduced only during week 1 in theTEM-treated group; pregnancy rates were reduced only duringweek 2 in the AA-exposed group and week 4 in the TEM-treatedgroup. Females were necropsied 13 days after the end of theappropriate mating week and the amount of pre- and post-implantationloss calculated. ACN treatment of male rats induced no increasesin either pre- or post-implantation loss in females in any ofthe 10 weeks post-exposure examined. AA induced significantlyelevated amounts of post-implantation loss for 3 weeks afterexposure and pre-implantation loss for 4 weeks post-exposure;both measures returned to control values for the remaining 6weeks of the study. The positive control TEM caused both indicesto increase during all 4 weeks examined. We conclude that AAis a dominant lethal mutagen in male rat germ cells in vivo,specifically in mature spermatozoa and late-stage spermatids.In contrast, the structurally related chemical ACN has neitherfertility nor dominant lethal effects in the male Fischer 344rat after oral administration, and may not pose a significantmutagenic risk to germ cells.