Examining risk assessment implications of genetic and dose-dependent dynamics of lead exposure in breastfeeding using the collaborative cross mouse population

Abstract

Breastfeeding offers well-documented advantages but may inadvertently introduce lead (Pb) exposure to infants. Scarce data exist on the risks of Pb exposure for breastfed infants, and strategies for risk mitigation are needed, particularly considering the heightened susceptibility of children to adverse effects from Pb exposure. To investigate the potential influence of breastfeeding on blood Pb levels (BLL) in offspring, population variation in BLL between nonparous and parous mouse dams was quantified, as well as in dams exposed to low and high dose while breastfeeding, and their offspring. Female mice from 14 distinct collaborative cross (CC) mouse strains were mated with sires from different CC strains to produce 14 F1 hybrids. Subsequently, dams were administered either low- (100 ppm) or high- (1,000 ppm) dose Pb through ad libitum access drinking water starting the day of delivery for a duration of 4 wk, leading to the subsequent exposure of the offspring via lactation. Genetic background emerged as a predominant factor contributing to variation, with substantial interstrain variability observed in both CC dams and F1 hybrids exposed to low and high doses of Pb. Crucially, the degree of variation in BLL among CC dams exceeded the default variability estimate (geometric SD = 1.6) utilized in regulatory standard settings. These findings underscore the importance of integrating population variability in risk assessment. Ultimately, this study provides critical insights to guide public health decision-making processes concerning Pb exposure through breastfeeding and its potential implications for infants' health.

Keywords: lead; maternal exposure; mouse model; risk assessment.