Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats

• Published in: Toxicology letters Vol. 375; pp. 69 - 76
• Main Authors: Vukelić, Dragana, Djordjevic, Aleksandra Buha, Anđelković, Milena, Repić, Aleksandra, Baralić, Katarina, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Boričić, Novica, Antonijević, Biljana, Bulat, Zorica
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-02-2023
• Subjects: Animals; Benchmarking; BMD; Dose-response; Essential metals; Lead - administration & dosage; Lead - toxicity; Low BLL; Male; Models, Animal; Rats; Rats, Wistar; Testis - chemistry; Testis - pathology; Testosterone; Testosterone - blood; BLL; BMDU; BMR; Low BLL; BMDL; EFSA; BMDI; Testosterone; Loglik; BMD; Dose-response; Essential metals; AIC; GSI
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2023.01.001

The objectives of the study were to simulate low-level Pb exposure scenario in an animal model and to examine reproductive adverse effects. Based on obtained data, we have performed Benchmark dose (BMD)-response modelling. Male Wistar rats were randomized in seven groups (n = 6): one control and six treated with: 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg body weight, daily for 28 days by oral gavage. The rats were sacrificed and the blood and testes were used for further analysis of testosterone levels in serum, testicular essential metal levels and histological analysis. The Pb treatment led to a dose-dependent decrease of serum testosterone levels with a negative trend (BMDI 0.17–6.13 mg Pb/kg). Increase of Zn (dose-dependent, BMDI 0.004–19.7 mg Pb/kg) and Cu and a decrease of Mn testicular levels were also detected with unscathed histology of the testes. The presented results might be used in further evaluation of the point of departure in human health risk assessment for Pb.
[Display omitted]
•Low-lead doses decreased testosterone serum levels.•Testicular Cu and Zn levels increased, while Mn levels decreased.•There were no histological changes in testis tissue.•The lowest BMD was calculated for increase of Zn testicular levels (0.004 mg Pb/kg b.w./day).•The obtained results provide useful data for further evaluation of Pb referent point.