van Raaij J A, van den Berg K J, Engel R, Bragt P C, Notten W R
TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
Toxicology. 1991 Mar 25;67(1):107-16. doi: 10.1016/0300-483x(91)90168-z.
Effects of administration of equimolar doses of hexachlorobenzene (HCB) and its metabolites pentachlorophenol (PCP) and tetrachlorohydroquinone (TCHQ) on serum thyroxine (TT4) and triiodothyronine (TT3) levels in rats were studied. Furthermore, it was investigated whether the observed effects were related to the serum levels of HCB or PCP. Rats received either corn oil (controls) or HCB, PCP or TCHQ in a single equimolar intraperitoneal dose of 0.056 mmol/kg. Results indicated that HCB did not alter serum TT4 and TT3 levels for a period up to 96 h after dosing. In contrast, PCP and TCHQ were both capable of reducing serum TT4 levels with a maximum effect between 6 and 24 h after exposure. TCHQ was more effective in repressing TT3 than TT4 blood levels. Dose-response experiments were carried out in order to obtain insight into the sensitivity of the observed effects. Rats received different doses of PCP or TCHQ intraperitoneally. The reductions of TT4 levels by PCP were inversely related to serum PCP levels in exposed animals, based on the toxicokinetics and dose-response profiles. Furthermore, PCP serum levels after HCB administration appeared too low to cause an effect. The results of this study indicate that not HCB itself, but rather its metabolites PCP and TCHQ may be involved in reduced serum thyroid hormone levels after HCB administration.
研究了给予等摩尔剂量的六氯苯(HCB)及其代谢产物五氯苯酚(PCP)和四氯对苯二酚(TCHQ)对大鼠血清甲状腺素(TT4)和三碘甲状腺原氨酸(TT3)水平的影响。此外,还研究了观察到的效应是否与血清中HCB或PCP的水平有关。大鼠接受玉米油(对照组)或HCB、PCP或TCHQ,腹腔内单次给予等摩尔剂量0.056 mmol/kg。结果表明,给药后长达96小时内,HCB未改变血清TT4和TT3水平。相比之下,PCP和TCHQ均能降低血清TT4水平,在暴露后6至24小时达到最大效应。TCHQ在抑制TT3方面比抑制TT4血药水平更有效。进行了剂量反应实验,以深入了解观察到的效应的敏感性。大鼠腹腔内接受不同剂量的PCP或TCHQ。根据毒代动力学和剂量反应曲线,暴露动物中PCP对TT4水平的降低与血清PCP水平呈负相关。此外,给予HCB后PCP的血清水平似乎过低,无法产生效应。本研究结果表明,HCB给药后血清甲状腺激素水平降低可能不是HCB本身,而是其代谢产物PCP和TCHQ所致。