Henderson R F, Sabourin P J, Bechtold W E, Steinberg B, Chang I Y
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Toxicol Appl Pharmacol. 1993 Nov;123(1):50-61. doi: 10.1006/taap.1993.1220.
Isobutene (2-methylpropene) (CAS No. 115-11-7) is a gas widely used in the chemical manufacturing industry. As an aid to planning long-term toxicity studies, research was conducted to determine the effect of exposure concentrations on the absorption and metabolism of isobutene in F344/N rats. Male F344/N rats (11-15 weeks of age) were exposed for 2 hr to 0, 40, 400, or 4000 ppm isobutene, and a time-course evaluation of blood levels of isobutene was performed using headspace analysis methods. Blood levels of isobutene were linearly related to exposure concentrations between 40 and 400 ppm but increased in a supralinear fashion at the highest concentration, suggesting that the capacity of the rats to metabolize isobutene had been exceeded. Total uptake, excretion patterns, and metabolic conversions were studied in rats exposed for up to 6 hr to 0, 2, 40, 400, or 4000 ppm [14C]isobutene. Absorption of the inhaled isobutene was approximately 8% up to 40 ppm isobutene, but decreased at the higher concentrations. The amount of isobutene metabolized per ppm.hr of exposure was also linear up to 40 ppm but decreased at higher concentrations. Over 90% of the absorbed isobutene was metabolized at exposure concentrations up to 400 ppm, but the exposure to approximately 4000 ppm isobutene resulted in approximately 20% of the absorbed dose exhaled as the unmetabolized isobutene. Two urinary metabolites were identified as isobutenediol and 2-hydroxyisobutyric acid. Two other urinary metabolites were tentatively identified as sulfate conjugates of isobutenediol. Based on these studies, linear dose-response relationships would be expected in chronic toxicity studies for exposures up to 40 ppm isobutene. Additional studies would be required to determine if repeated exposures would induce higher metabolic capacities in the exposed rats.
异丁烯（2-甲基丙烯）（化学物质登记号：115 - 11 - 7）是一种在化学制造业中广泛使用的气体。为辅助规划长期毒性研究，开展了相关研究以确定暴露浓度对F344/N大鼠体内异丁烯吸收和代谢的影响。将雄性F344/N大鼠（11 - 15周龄）暴露于0、40、400或4000 ppm的异丁烯中2小时，并使用顶空分析法对异丁烯的血液水平进行时间进程评估。异丁烯的血液水平在40至400 ppm之间与暴露浓度呈线性相关，但在最高浓度时呈超线性增加，这表明大鼠代谢异丁烯的能力已被超出。在暴露于0、2、40、400或4000 ppm [¹⁴C]异丁烯长达6小时的大鼠中研究了总摄取量、排泄模式和代谢转化情况。吸入的异丁烯在异丁烯浓度达40 ppm时吸收约8%，但在更高浓度时吸收减少。每ppm·小时暴露量下代谢的异丁烯量在40 ppm时也呈线性，但在更高浓度时减少。在暴露浓度达400 ppm时，超过90%的吸收异丁烯被代谢，但暴露于约4000 ppm异丁烯时，约20%的吸收剂量以未代谢的异丁烯形式呼出。两种尿代谢物被鉴定为异丁烯二醇和2 - 羟基异丁酸。另外两种尿代谢物被初步鉴定为异丁烯二醇的硫酸盐共轭物。基于这些研究，预计在异丁烯暴露量达40 ppm的慢性毒性研究中会出现线性剂量反应关系。需要进一步研究以确定重复暴露是否会诱导暴露大鼠产生更高的代谢能力。
