Lloyd S C, Blackburn D M, Foster P M
Imperial Chemical Industries PLC, Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom.
Toxicol Appl Pharmacol. 1988 Mar 15;92(3):390-401. doi: 10.1016/0041-008x(88)90179-2.
Trifluoroethanol (TFE) and trifluoroacetaldehyde (TFALD) produced a reduction in testis weight 3 days after a single oral dose of 10 mg/kg. In contrast, administration of trifluoroacetic acid (TFAA) caused no observable testicular effects. Reduction in testis weight was accompanied by morphological changes, involving specific damage to pachytene and dividing spermatocytes, and round spermatids. In an in vitro Sertoli/germ cell co-culture system, only TFALD was found to produce dose-related effects at concentrations of 10(-3) and 10(-4) M. There was increased germ cell loss from the cultures, particularly loss of pachytene and dividing spermatocytes, accompanied by leakage of the pachytene spermatocyte marker enzyme, lactate dehydrogenase-X. TFE and TFAA did not produce these effects in the culture system at concentrations equimolar with TFALD. These results suggest that TFALD may play a critical role in the development of the testis lesion seen with TFE in vivo. The effects seen both in vivo and in vitro were remarkably similar to those previously reported for another substituted alcohol and its metabolites, ethylene glycol monomethyl ether. It is postulated that the two series of compounds may have a similar mode of action on rat testis.
单次口服剂量为10毫克/千克的三氟乙醇（TFE）和三氟乙醛（TFALD）在给药3天后可使睾丸重量减轻。相比之下，给予三氟乙酸（TFAA）未引起明显的睾丸效应。睾丸重量减轻伴随着形态学变化，包括对粗线期和正在分裂的精母细胞以及圆形精子细胞的特异性损伤。在体外支持细胞/生殖细胞共培养系统中，仅发现TFALD在浓度为10⁻³和10⁻⁴M时产生剂量相关效应。培养物中的生殖细胞损失增加，特别是粗线期和正在分裂的精母细胞的损失，同时伴有粗线期精母细胞标记酶乳酸脱氢酶-X的泄漏。TFE和TFAA在与TFALD等摩尔浓度的情况下在培养系统中未产生这些效应。这些结果表明，TFALD可能在体内TFE所致睾丸损伤的发生中起关键作用。体内和体外观察到的效应与先前报道的另一种取代醇及其代谢产物乙二醇单甲醚的效应非常相似。据推测，这两类化合物对大鼠睾丸可能具有相似的作用模式。
