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A unit risk factor (URF) was developed for isoprene based on evaluation of three animal studies with adequate data to perform dose–response modeling (NTP, 1994, 1999; Placke et al., 1996). Ultimately, the URF of 6.2E-08 per ppb (2.2E-08 per μg/m3) was based on the 95% lower confidence limit on the effective concentration corresponding to 10% extra risk for liver carcinoma in male B6C3F1 mice after incorporating appropriate adjustment factors for species differences in target tissue metabolite concentrations and inhalation dosimetry. The corresponding lifetime air concentration at the 1 in 100,000 no significant excess risk level is 160 ppb (450 μg/m3). This concentration is almost 4400 times lower than the lowest exposure level associated with statistically increased liver carcinoma in B6C3F1 mice in the key study (700 ppm in Placke et al., 1996) and is above typical isoprene breath concentrations reported in the scientific literature. Continuous lifetime environmental exposure to the 1 in 100,000 excess risk level of 160 ppb would be expected to raise the human blood isoprene area under the curve (AUC) less than one-third of the standard deviation of the endogenous mean blood AUC. The mean for ambient air monitoring sites in Texas (2005–2014) is approximately 0.13 ppb.An inhalation URF of 6.2E-08 per ppb (2.2E-08 per μg/m3) was derived for isoprene.The cancer endpoint was liver carcinoma in B6C3F1 mice in Placke et al. (1996).Adjustments were made for interspecies differences in metabolism and dosimetry.The 10−5 excess risk air concentration is 160 ppb, above typical breath levels.Mean for ambient air monitoring sites in Texas (2005–2014) is approximately 0.13 ppb.