Gestational and early postnatal exposure to a mixture of organophosphate ester flame retardants found in Canadian house dust on hindlimb skeletal development in postnatal day 4 rats

Abstract

Background: Ever since organophosphate esters (OPEs) became the mainstream replacement for organobromine compounds in fire retardants (FRs), numerous studies have explored their potential as endocrine disruptors and developmental toxicants. The purpose of this study is to investigate the impact of gestational and early postnatal exposure of OPE mixtures on the ossification of hindlimb phalangeal in postnatal day 4 (PND4) rat pups, as the amount of OPEs within the diet mixture is relative to its composition in Canadian household dust.Methods: Male and female adult Charles River Sprague-Dawley rats were exposed to OPE mixtures for 70 and 21 days, respectively. The OPE doses were determined to be 10x, 1,000x, and 30,000x the relative human exposure. The progenies were exposed to OPEs both gestationally (~21 days) and lactationally (4 days). At least 2 of each sex from each litter were sacrificed and processed at PND4 for skeletal staining using Alizarin red and Alcian blue. The samples were analyzed and compared against a reference sample to examine any abnormalities in ossification.Results: At PND4, there is no significant effect of OPEs on the number of pups with abnormal ossification between the control and treatment groups. High doses of OPEs, at concentrations 30,000x of relative human exposures, showed a significant increase in the severity of delay of ossification at the middle phalanx of PND4 pups.Limitations: Due to the limitation of small sample sizes (litter n=6-7) and a wide variance in data, there is no clear evidence on whether OPE exposure induces greater incidences of abnormal ossification in the digits of PND4 pups.Conclusion: There is a delay in ossification from OPE exposure at the high dose (30,000x).