A Health Risk Benchmark for the Neurologic Effects of Styrene: Comparison with NOAEL/LOAEL Approach

Benchmark dose (BMD) analysis was used to estimate an inhalation benchmark concentration for styrene neurotoxicity. Quantal data on neuropsychologic test results from styrene‐exposed workers [Mutti et al. (1984). American Journal of Industrial Medicine, 5, 275–286] were used to quantify neurotoxicity, defined as the percent of tested workers who responded abnormally to ≥1, ≥2, or ≥3 out of a battery of eight tests. Exposure was based on previously published results on mean urinary mandelic‐ and phenylglyoxylic acid levels in the workers, converted to air styrene levels (15, 44, 74, or 115 ppm). Nonstyrene‐exposed workers from the same region served as a control group. Maximum‐likelihood estimates (MLEs) and BMDs at 5 and 10% response levels of the exposed population were obtained from lognormal analysis of the quantal data. The highest MLE was 9 ppm (BMD = 4 ppm) styrene and represents abnormal responses to ≥3 tests by 10% of the exposed population. The most health‐protective MLE was 2 ppm styrene (BMD = 0.3 ppm) and represents abnormal responses to ≥1 test by 5% of the exposed population. A no observed adverse effect level/lowest observed adverse effect level (NOAEL/LOAEL) analysis of the same quantal data showed workers in all styrene exposure groups responded abnormally to ≥1, ≥2, or ≥3 tests, compared to controls, and the LOAEL was 15 ppm. A comparison of the BMD and NOAEL/LOAEL analyses suggests that at air styrene levels below the LOAEL, a segment of the worker population may be adversely affected. The benchmark approach will be useful for styrene noncancer risk assessment purposes by providing a more accurate estimate of potential risk that should, in turn, help to reduce the uncertainty that is a common problem in setting exposure levels.