Dominant Lethal Assay of 2,4-Pentanedione Vapor in Fischer 344 Rats

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Abstract
2,4-Pentanedione (2,4-PD: CAS No. 123-54-6) is a volatile industrial chemical of moderate acute toxicity, centrally neurotoxic by repeated exposure to high vapor concentrations, fetotoxic, and clastogenic. Its wide use and known toxicology indicated the conduct of a dominant lethal assay. Male Fischer 344 rats, 20 per group, were exposed to 2,4-PD vapor concentrations (mean ± SD) of 0, 99.1 ± 2.2, 412 ± 12.6 and 694 ± 9.1 ppm, for 6 hr/day for 5 consecutive days. The day following the final exposure they were bred to unexposed female Fischer 344 rats, 2 per week for 8 consecutive weeks. Weight loss occurred with males during 2,4-PD exposure for the 412 and 694 ppm groups, with compensatory increased weight at 694 ppm, for the first two weeks postexposure. No histopathological change was seen in brain, testes or thymus from high concentration males sacrificed after eight weeks of mating. Minor transient reproductive and gestational effects were present at 412 and 694 ppm. At week 2 there was a reduction, not statistically significant, in the number of corpora lutea and total and viable implants per dam at 694 ppm, and a slight increase in preimplantation loss. At week 3 the number of pregnant females was slightly reduced at 412 and 694 ppm, causing a lowered female fertility index. At week 4 there was a slight reduction in the number of total and viable implants per litter and a significant preimplantation loss at 694 ppm. The dominant lethal factor (FL%) was increased slightly at 694 ppm for weeks 2 and 4. Thus, the “no observable effect” level for dominant lethal effects was 99 ppm. The results, although not statistically significant, are dose-related and compatible with a transient slight dominant lethal effect at the spermatid stage of spermatogenesis.