Lithium Carbonate: Updated Reproductive and Developmental Toxicity Assessment Using Scientific Literature and Guideline Compliant Studies

Toxicology. 2021 Aug 26:152907. doi: 10.1016/j.tox.2021.152907. Online ahead of print.ABSTRACTThe current publication describes most recent so far unpublished (key) guideline and GLP compliant reproductive and developmental toxicity studies of lithium carbonate in rats, including their interpretation and conclusions in terms of human hazard assessment when compared to existing literature. Particular attention was paid to the target organs and dose response of lithium ion related effects to differentiate between a primary (pharmacokinetic/pharmacodynamic) action and secondary effects as a result of systemic and target organ toxicity. In the key two-generation reproductive toxicity (OECD TG 416) study in rats, doses of 5, 15 and 45 mg/kg bw/d (0.95, 2.9 and 8.6 mg Li+/kg bw/d) were given by oral gavage, resulting in clear NOAELs of 15 mg/kg bw/d (2.9 mg Li+/kg bw/d) for systemic parental toxicity and 45 mg/kg bw/d (8.6 mg Li+/kg bw/d) for reproductive toxicity and fetal toxicity. Target organ changes were consistently observed in liver (cytoplasmic rarefaction) and kidney (dilated tubuli). In the key developmental toxicity (OECD TG 414) study in rats, doses given by oral gavage were 10, 30 and 90 mg/kg bw/d (1.9, 5.7 and 17.1 mg Li+/kg bw/d) was investigated resulting in NO(A)ELs of 30 mg/kg bw/d (5.7 mg Li+/kg bw/d) (maternal toxicity) and 90 mg/kg bw/d (17 mg Li+/kg bw/d) (fetal toxicity and teratogenicity). The highest dose of 90 mg/kg bw/day resulted in clear signs of toxic...
Source: Toxicology - Category: Toxicology Authors: Source Type: research