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BackgroundBenzene is a human hematotoxicant and a leukemogen that causes lymphohematopoietic cancers, especially acute myelogenous leukemia. We investigated uptake of benzene in hookah smokers and non-smokers attending hookah social events in naturalistic settings where hookah tobacco was smoked exclusively.MethodsWe quantified S-phenylmercapturic acid (SPMA), a metabolite of benzene, in the urine of 105 hookah smokers and 103 non-smokers. Participants provided spot urine samples the morning of and the morning after attending an indoor hookah-only smoking social event at a hookah lounge or in a private home.ResultsUrinary SPMA levels in hookah smokers increased significantly following a hookah social event (P < 0.001). This increase was 4.2 times higher after hookah lounge events (P < 0.001) and 1.9 times higher after home events (P = 0.003). In non-smokers, urinary SPMA levels increased 2.6 times after hookah lounge events (P = 0.055); however, similar urinary SPMA levels were detected before and after home events, possibly indicating chronic exposure to benzene (P = 0.933).ConclusionsOur data provide the first evidence for uptake of benzene in hookah smokers and non-smokers exposed to hookah tobacco secondhand smoke at social events in private homes compared with their counterparts in hookah lounges. Hookah tobacco smoke is a source of benzene exposure, a risk factor for leukemia.ImpactBecause there is no safe level of exposure to benzene, our results call for interventions to reduce or prevent hookah tobacco use, regulatory actions to limit hookah-related exposure to toxicants including benzene, initiate labeling of hookah-related products, and include hookah smoking in clean indoor air legislation.