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大鼠对1,3 - 二苯基胍的皮肤吸收与分布

Dermal absorption and disposition of 1,3-diphenylguanidine in rats.

作者信息

Shah P V, Sumler M R, Ioannou Y M, Fisher H L, Hall L L

出版信息

J Toxicol Environ Health. 1985;15(5):623-33. doi: 10.1080/15287398509530691.

DOI:10.1080/15287398509530691
PMID:4046069
Abstract

Dermal absorption, distribution, and metabolism of 1,3-diphenylguanidine (CAS 102-06-7) (DPG), widely used as an accelerator in processing rubber and in food packaging, was studied in adult female Sprague-Dawley rats. DPG shows 10% penetration through clipped back skin of the rats in 5 d. The first-order dermal absorption rate constant as determined by least square method was 0.021 +/- 0.002 d-1 (T1/2 = 33.6 d). Approximately 13% of the absorbed dose remained in the body in 5 d. Retention in skin, muscle, liver, intestine and fat contributed most to the body burden of DPG-derived radioactivity in 5 d. All tissues showed tissue to blood ratios greater than 1, with liver and intestine ratios of 26 at 5 d. Approximately 61% of the absorbed dose was eliminated into urine and 27% into feces in 5 d showing rapid clearance of absorbed DPG from the body. High-pressure liquid chromatography (HPLC) analysis of urine revealed two major peaks [parent compound and metabolite(s)]. Within 72 h, approximately 50% of the DPG-derived radioactivity excreted in the urine was parent compound. After 72 h, the DPG-derived radioactivity in the urine was present in the form of a single metabolite, and no parent compound was detected. No parent compound was detected in feces. Two metabolites, neither of which occurred in urine, were detected in feces. The HPLC analysis of the radioactivity at the application site showed only parent compound. Even though DPG shows slow dermal penetration, this route of exposure needs to be considered in the risk assessments because of the suspected chronic toxicity of DPG.

摘要

1,3 - 二苯基胍(CAS 102 - 06 - 7)(DPG)广泛用作橡胶加工和食品包装中的促进剂,本研究在成年雌性Sprague - Dawley大鼠中对其皮肤吸收、分布和代谢情况进行了考察。DPG在5天内透过大鼠背部剪毛皮肤的渗透率为10%。通过最小二乘法确定的一级皮肤吸收速率常数为0.021±0.002 d⁻¹(半衰期 = 33.6天)。在5天内,约13%的吸收剂量留存于体内。皮肤、肌肉、肝脏、肠道和脂肪中的留存对5天内DPG衍生放射性的体内负荷贡献最大。所有组织的组织与血液比值均大于1,肝脏和肠道在第5天的比值为26。在5天内,约61%的吸收剂量经尿液排出,27%经粪便排出,表明吸收的DPG能从体内快速清除。尿液的高压液相色谱(HPLC)分析显示有两个主要峰[母体化合物和代谢物(一种或多种)]。在72小时内,尿液中排出的DPG衍生放射性约50%为母体化合物。72小时后,尿液中DPG衍生放射性以单一代谢物的形式存在,未检测到母体化合物。粪便中未检测到母体化合物。在粪便中检测到两种尿液中未出现的代谢物。应用部位放射性的HPLC分析仅显示有母体化合物。尽管DPG的皮肤渗透较慢,但鉴于其可疑的慢性毒性,在风险评估中仍需考虑这种暴露途径。

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