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

Acrylonitrile (ACN) and acrylamide (AA), structurally similar vinyl monomers, are both animal carcinogens. ACN is weakly mutagenic in bacteria and induces sister-chromatid exchange, unscheduled DNA synthesis and cell transformation in cells in culture. AA induces chromosomal aberrations in bone marrow, blood and germ cells in vivo, and dominant lethal mutations in the germ cells of male mice and rats. In the current study, the ability of AA and ACN to induce dominant lethal mutations in the germ cells of male Fischer 344 rats was compared. Three groups of 50 males were gavaged daily for 5 days with ACN (60 mg/kg in normal saline), AA (30 mg/kg in normal saline) or vehicle only; an additional group of 20 males received a single i.p. injection of 0.2 mg/kg triethylenemelamine (TEM) on the afternoon of day 5. Starting 1 day after exposure, each male was bred to one female per week for 4 weeks (TEM-exposed group) or 10 weeks (ACN, AA and control groups). Mating rates were reduced only during week 1 in the TEM-treated group; pregnancy rates were reduced only during week 2 in the AA-exposed group and week 4 in the TEM-treated group. Females were necropsied 13 days after the end of the appropriate mating week and the amount of pre- and post-implantation loss calculated. ACN treatment of male rats induced no increases in either pre- or post-implantation loss in females in any of the 10 weeks post-exposure examined. AA induced significantly elevated amounts of post-implantation loss for 3 weeks after exposure and pre-implantation loss for 4 weeks post-exposure; both measures returned to control values for the remaining 6 weeks of the study. The positive control TEM caused both indices to increase during all 4 weeks examined. We conclude that AA is 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 neither fertility nor dominant lethal effects in the male Fischer 344 rat after oral administration, and may not pose a significant mutagenic risk to germ cells.