PNNL

Abstract

Background: Polybrominated diphenyl ethers (PBDEs) are ubiquitous in the environment, with well-documented and widespread human exposure. A recent systematic review and meta-analysis of human studies found an association between prenatal serum PBDE concentrations and a decrease in the IQ of children. Objective: Our goal was to demonstrate the application of systematic review methods, including meta-analysis (if possible), to animal toxicology data to draw conclusions about hazard. We performed a systematic review of experimental animal studies on the neurotoxicity of PBDEs following developmental exposure. Outcomes assessed included measures related to learning, memory, and attention, which parallel the intelligence-related outcomes evaluated in the systematic review of human studies. Methods: We searched PubMed, Embase, and Toxline for experimental studies in non-human mammals published in English through August 15, 2016. Evaluation of risk of bias and the overall body of evidence followed guidance developed by the National Toxicology Program’s Office of Health Assessment and Translation (OHAT). Results: The animal data on PBDEs and learning, memory, and attention were available for BDEs 47, 99, 153, 203, 206, and 209 and the technical mixture DE-71. These data were diverse and complex, with studies using varying designs and outcomes. There were concerns about risk of bias for many studies, and study reporting of methods and results was often incomplete. A meta-analysis of six studies showed consistent evidence of an increase in latency (effect size of 25.8 [CI, 20.3 to 31.2]) in the last trial of the Morris water maze in PBDE-exposed animals, with low heterogeneity. However, for most endpoints, there were unexplained inconsistencies across studies. There was also no consistent evidence of a dose-response relationship. Conclusions: Our analyses illustrates the application of systematic review methods to a chemical hazard assessment. There is a moderate level of evidence that exposure to BDEs 47, 99, and 209 affects learning. For other PBDEs and other endpoints, the level of evidence was low or very low. The meta-analysis led to stronger conclusions than would have been drawn based on a qualitative review of the evidence. The systematic review also identified factors that increased concerns about risk of bias in individual studies that might be remedied by better study reporting.