Hubbs A F, Castranova V, Ma J Y, Frazer D G, Siegel P D, Ducatman B S, Grote A, Schwegler-Berry D, Robinson V A, Van Dyke C, Barger M, Xiang J, Parker J
National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Toxicol Appl Pharmacol. 1997 Mar;143(1):37-46. doi: 10.1006/taap.1996.8053.
Following a formulation change, a leather conditioner was involved in a 1992 nationwide outbreak of respiratory illness. We investigated the composition and toxicity of the conditioner produced before (previous product) and after (new product) the disease outbreak. The new product induced tachypnea, pulmonary edema, pulmonary hemorrhage, and sporadic deaths in exposed guinea pigs and rats. Ultrastructurally, these changes were associate with direct pulmonary cytotoxicity characterized by necrosis of alveolar type I cells and alveolar septal interstitial edema. Chemical analyses suggested major alterations in the fluorohydrocarbon constituents in the new formulation of the leather conditioner. While these alterations could not be specifically identified, they appeared to include changes from fluoralkanes to fluoroalkenes, fluorophenyl, and/or fluoroalcohol compounds. Changes in solvent composition were consistent with traces of 2-butoxyethanol and isomers of dipropylene glycol methyl ether, and additional C10-C12 alkanes. In this study, we demonstrated the toxicity of the new product in laboratory animals. Some of the altered constituents of the new product have been identified and are potential candidates for additional investigations to identify specific etiologic agents.
在一次配方变更后,一种皮革护理剂引发了1992年全国范围的呼吸道疾病暴发。我们调查了疾病暴发前(旧产品)和暴发后(新产品)生产的护理剂的成分和毒性。新产品在暴露的豚鼠和大鼠中引起呼吸急促、肺水肿、肺出血和散发性死亡。在超微结构上,这些变化与直接的肺细胞毒性相关,其特征为I型肺泡细胞坏死和肺泡间隔间质水肿。化学分析表明皮革护理剂新配方中的氟代烃成分有重大改变。虽然这些改变无法具体确定,但似乎包括从氟代烷烃转变为氟代烯烃、氟代苯基和/或氟代醇化合物。溶剂成分的变化与痕量的2-丁氧基乙醇和二丙二醇甲醚异构体以及额外的C10 - C12烷烃一致。在本研究中,我们证明了新产品对实验动物的毒性。新产品中一些改变的成分已被确定,是进一步调查以确定特定病原体的潜在候选物。