磷酸三(1,3-二氯异丙基)酯对大鼠的急性和亚慢性毒性作用

doi:10.3969/j.issn.1004-616x.2023.06.005

Abstract

Abstract: OBJECTIVE：To investigate the acute and sub-chronic toxicity of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) in rats. METHODS：In the acute toxicity test，50 SD rats at SPF level were randomly divided into 5 groups，with 10 rats per group，equally male and female，and given a single oral dose of 464，1 000，2 150，4 640，and 10 000 mg/kg. In the sub-chronic toxicity test，80 SD rats at the SPF level were randomly divided into 4 groups of 20 rats per group，equally divided between males and females，and orally administered a dose of 0，13.3，40，and 120 (high dose) mg/kg per day for 112 consecutive days. Organs were harvested and weighed，and the organ coefficient was calculated. Blood routine and blood biochemical indices were examined. HE staining was performed to analyze histopathological changes. Representative indicators were selected for toxic effects using the baseline dose BMD method to assess exposure levels at specific risk levels，compared with the NOAEL method reference values to analyze relatively more specific and sensitive dose limits. RESULTS：The LD₅₀ of TDCIPP in acute oral toxicity test in SD rats was 2 000-2 300 mg/kg. Compared with the control group，the 120 mg/(kg·d) sub-chronic exposure dose significantly affected the body mass growth of female rats；the organ coefficients of the liver and kidney of rats in the 40 and 120 mg/(kg·d) dose of TDCIPP group were significantly elevated (P<0.05)；and the leukocyte counts，lymphocyte counts，and monocyte counts of male rats in the 40 mg/(kg·d) dose of TDCIPP group were significantly elevated (P<0.05). The mean values of white blood cell count，lymphocyte count，monocyte count and eosinophil count in male rats dosed with 40 mg/(kg·d) were significantly higher than those in the control group (P<0.05). The mean values of AST in male rats were significantly lower than those in the control group in the 40 mg/(kg·d) dose group；the mean values of ALT and AST in female rats in the 40 mg/(kg·d) dose group were significantly lower than those in the control group (P<0.05)；and HE staining of the 40 and 120 mg/(kg·d) dose groups showed significant renal pathology damage. The highest NOAEL of 13.3 mg/(kg·d) was assessed based on the no-observed-adverse-effects level (NOAEL). The benchmark dose method (BMD)，which uses blood creatinine as an indicator of renal function，determined the reference dose in the risk assessment with a limit of 2.696 mg/(kg·d). CONCLUSION：The livers and kidneys were the main target organs of TDCIPP in rats.

Key words: tris phosphate, acute toxicity, subchronic toxicity, organ coefficients, LD₅₀

CLC Number:

R994.6

ZHANG Jiuhong, CHEN Xiao, ZHAO Jing, XU Benhong, WU Desheng, LIU Jianjun. Acute and sub-chronic toxicity of tris(1, 3-dichloroisopropyl) phosphate in rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(6): 431-438.

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Acute and sub-chronic toxicity of tris(1, 3-dichloroisopropyl) phosphate in rats

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