Identification of sensitive endpoints for the assessment of phthalates-induced reproductive and developmental toxicity: A literature mining study

Kai Li; Yiping Zhang; Ludi Li; Kanglong Cui; Yingzi Li; Chunying Li; Yufei Dai; Wusheng Xiao; Qi Wang

doi:10.1016/j.fct.2024.114686

Identification of sensitive endpoints for the assessment of phthalates-induced reproductive and developmental toxicity: A literature mining study

Food Chem Toxicol. 2024 Apr 23:188:114686. doi: 10.1016/j.fct.2024.114686. Online ahead of print.

Authors

Kai Li¹, Yiping Zhang¹, Ludi Li¹, Kanglong Cui¹, Yingzi Li¹, Chunying Li², Yufei Dai³, Wusheng Xiao⁴, Qi Wang⁵

Affiliations

¹ Department of Toxicology, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
² Peking University Health Science Library, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
³ National Institute of Environmental Health, China CDC, 7 Panjiayuan South Li, Chaoyang District, Beijing, 100021, China. Electronic address: daiyf@chinacdc.cn.
⁴ Department of Toxicology, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China; Key Laboratory of State Administration of Traditional Chinese Medicine for Compatibility Toxicology, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. Electronic address: wxiao@bjmu.edu.cn.
⁵ Department of Toxicology, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China; Key Laboratory of State Administration of Traditional Chinese Medicine for Compatibility Toxicology, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. Electronic address: wangqi@bjmu.edu.cn.

PMID: 38663762
DOI: 10.1016/j.fct.2024.114686

Abstract

Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), two common types of phthalates, are known to cause reproductive and developmental toxicity in animals and humans. The reference doses (RfD) of DBP and DEHP should be determined by sensitive endpoints. We here aimed to identify sensitive endpoints for DBP- and DEHP-induced such toxicity using published literatures. By examining the impacts of maternal exposure to DBP or DEHP on anogenital distance (AGD) and semen quality of offspring, we discovered that DBP or DEHP caused AGD decline in boys but increase in girls with DBP being more potent and the first 14weeks of pregnancy being more susceptible, suggesting a chemical- and time-dependent phenomenon. We also identified AGD shortening and total sperm count reduction as two sensitive endpoints for DBP- or DEHP-induced reproductive and developmental toxicity, respectively. Based upon these two endpoints and the employment of the Bayesian benchmark dose approach with an uncertainty factor of 3,000, we estimated the RfD values of DBP and DEHP were 15 μg/kg/day and 36 μg/kg/day, respectively. Thus, we uncover previously unrecognized phenomena of DBP- or DEHP-induced reproductive and developmental toxicity and establish new and comparable or more conservative RfDs for the risk assessment of phthalates exposure in humans.

Keywords: Anogenital distance; DBP; DEHP; Reference dose; Total sperm count.