A systematic review of nervous system effects of ethylbenzene exposure in animal models

Ethylbenzene is a high-production-volume chemical. Exposure occurs in the general population, but there is potential for additional exposure in certain groups, such as workers in petrochemical industries or individuals living near contaminated areas. This paper presents a systematic review of currently available evidence in animals focused on potential nervous system-related effects of ethylbenzene exposure. A broad literature search was conducted. A total of 9,679 studies were screened for inclusion based on Populations, Exposures, Comparators, and Outcomes (PECO) criteria. Included studies were evaluated for potential concerns related to risk of bias and sensitivity, and informative studies moved forward for data extraction and evidence synthesis. Twenty-one animal toxicology studies were identified that evaluated nervous system effects, including auditory effects, neurotransmitters, neurobehavior, brain weight, and histopathology. Six studies rated medium or low confidence showed consistent concentration- and exposure duration-related effects on cochlear hair cells and hearing thresholds. The evidence for the other nervous system outcomes is inconclusive. Although some studies showed effects on neurotransmitters and neurobehavior, they were rated low confidence, and findings were inconsistent. Relative brain weight changes were observed, but the direction of the effect was inconsistent. No changes were observed in absolute brain weights, which is considered the more reliable measure for evaluating effects on brain weight. No changes in brain histopathology were reported.