The use of biomonitoring data in exposure and human health risk assessment: benzene case study

Abstract

A framework of “Common Criteria” (i.e. a series of questions) has been developed to inform the use and evaluation of biomonitoring data in the context of human exposure and risk assessment. The data-rich chemical benzene was selected for use in a case study to assess whether refinement of the Common Criteria framework was necessary, and to gain additional perspective on approaches for integrating biomonitoring data into a risk-based context. The available data for benzene satisfied most of the Common Criteria and allowed for a risk-based evaluation of the benzene biomonitoring data. In general, biomarker (blood benzene, urinary benzene and urinary S-phenylmercapturic acid) central tendency (i.e. mean, median and geometric mean) concentrations for non-smokers are at or below the predicted blood or urine concentrations that would correspond to exposure at the US Environmental Protection Agency reference concentration (30 µg/m3), but greater than blood or urine concentrations relating to the air concentration at the 1 × 10−5 excess cancer risk (2.9 µg/m3). Smokers clearly have higher levels of benzene exposure, and biomarker levels of benzene for non-smokers are generally consistent with ambient air monitoring results. While some biomarkers of benzene are specific indicators of exposure, the interpretation of benzene biomonitoring levels in a health-risk context are complicated by issues associated with short half-lives and gaps in knowledge regarding the relationship between the biomarkers and subsequent toxic effects.

Avaliação ambiental de BTEX (benzeno, tolueno, etilbenzeno, xilenos) e biomarcadores de genotoxicidade em trabalhadores de postos de combustíveis

“…Confirmando essa suposição, Vlaanderen et al 40 realizaram um estudo de metanálise por metarregressão com o objetivo de avaliar a curva dose--resposta benzeno e risco de leucemia, sendo indicado pelo modelo uma forma supralinear da curva dose-resposta na região de baixas doses de exposição ao benzeno. Provavelmente, esse resultado de maior risco de leucemia em baixas doses ocorre pelo benzeno ser mais eficientemente metabolizado em baixas concentrações, aumentando a produção de seus metabólitos reativos, que são hematotóxicos [41][42][43][44] .…”

Benzene Uptake in Hookah Smokers and Non-smokers Attending Hookah Social Events: Regulatory Implications

“…These results suggest that hookah tobacco smoking may be a risk factor for leukemia. Although leukemia may result from chronic multiple and interacting environmental and genetic components, it is recommended that exposure to benzene should be minimized (36,39,40).…”

“…38). Benzene exposure can be monitored by SPMA, a minor metabolite of benzene and a highly specific urinary biomarker (39,40). Only 0.11% (0.05%-0.26%) of inhaled benzene is metabolized to SPMA, which has a short half-life; mean ranges from 9 to 13 hours (39)(40)(41).…”

“…Benzene exposure can be monitored by SPMA, a minor metabolite of benzene and a highly specific urinary biomarker (39,40). Only 0.11% (0.05%-0.26%) of inhaled benzene is metabolized to SPMA, which has a short half-life; mean ranges from 9 to 13 hours (39)(40)(41). Cigarette smoking is regarded as a source of benzene intake and an established risk factor for adult acute myelogenous leukemia (42)(43)(44)(45)(46)(47)(48)(49).…”

The role of human biological monitoring in health risk assessment

“…For example, phenol is one of the major metabolites of benzene. However, urinary phenol measurement is not a good indicator of benzene exposure as phenol also occurs naturally and can be found in other exposures such as cigarette smoke (McDonald et al, 2001;Arnold et al, 2013). Non-specificity could also arise from endogenous production of a biomarker in the body (e.g., ethylene oxide).…”