Tyl R W, Ballantyne B, Fisher L C, Tarasi D J, Dodd D E
Bushy Run Research Center, Union Carbide Corporation, Export, Pennsylvania.
Toxicol Ind Health. 1989 May;5(3):463-77. doi: 10.1177/074823378900500307.
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.
2,4 - 戊二酮（2,4 - PD：化学物质登记号123 - 54 - 6）是一种具有中等急性毒性的挥发性工业化学品，反复接触高浓度蒸汽会导致中枢神经毒性、胚胎毒性和致染色体断裂性。鉴于其广泛使用以及已知的毒理学特性，开展了显性致死试验。每组20只雄性Fischer 344大鼠，分别暴露于浓度（均值±标准差）为0、99.1±2.2、412±12.6和694±9.1 ppm的2,4 - PD蒸汽中，每天暴露6小时，连续暴露5天。末次暴露后的次日，将它们与未暴露的雌性Fischer 344大鼠交配，连续8周，每周交配2次。412 ppm和694 ppm组的雄性大鼠在2,4 - PD暴露期间体重减轻，694 ppm组在暴露后的前两周体重有代偿性增加。交配8周后处死的高浓度组雄性大鼠，其脑、睾丸或胸腺未观察到组织病理学变化。412 ppm和694 ppm组出现轻微的短暂生殖和妊娠效应。在第2周，694 ppm组每只母鼠的黄体数、总着床数和存活着床数减少，但差异无统计学意义，着床前损失略有增加。在第3周，412 ppm和694 ppm组怀孕雌性数量略有减少，导致雌性生育指数降低。在第4周，694 ppm组每窝的总着床数和存活着床数略有减少，着床前损失显著增加。在第2周和第4周，694 ppm组的显性致死率（FL%）略有增加。因此，显性致死效应的“无可见效应”水平为99 ppm。这些结果虽然无统计学意义，但与剂量相关，并且与精子发生的精子细胞阶段出现的短暂轻微显性致死效应相符。
