title: Development of an inhalation unit risk factor for isoprene.
abstract: 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/m(3)) 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/m(3)). 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.
authors.affiliation: Texas Commission on Environmental Quality (TCEQ), Toxicology Division, MC-168, P.O. Box 13087, Austin, TX 78711, United States. Electronic address: Joseph.Haney@tceq.texas.gov.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Haney
authors.affiliation: Texas Commission on Environmental Quality (TCEQ), Toxicology Division, MC-168, P.O. Box 13087, Austin, TX 78711, United States. Electronic address: Tracie.Phillips@tceq.texas.gov.
authors.forename: Tracie
authors.initials: T
authors.lastname: Phillips
authors.affiliation: Sielken & Associates Consulting, Inc., 3833 Texas Avenue, Bryan, TX 77802, United States. Electronic address: SielkenAssoc@aol.com.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sielken
authors.affiliation: Texas A&M University, 4073 Emerging Technologies Building, 3131 TAMU, College Station, TX 77843, United States. Electronic address: Ciriacov@tamu.edu.
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Valdez-Flores
mesh_terms: D000393:Air Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D019540:Area Under Curve; D002070:Butadienes / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D063646:Carcinogenesis / Q000139:chemically induced*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring / Q000379:methods; D005260:Female; D045782:Hemiterpenes / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D016014:Linear Models; D008297:Male; D051379:Mice; D008962:Models, Theoretical; D009369:Neoplasms / Q000139:chemically induced*; D010420:Pentanes / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D011916:Rats, Inbred F344; D018570:Risk Assessment; D012307:Risk Factors; D013045:Species Specificity; D013781:Texas; D013997:Time Factors; D035501:Uncertainty
chemical_list: D000393:Air Pollutants; D002070:Butadienes; D002273:Carcinogens; D045782:Hemiterpenes; D010420:Pentanes; C005059:isoprene
keywords: Cancer; Carcinogenicity; Inhalation; Isoprene; Liver; Regulatory; Toxicity; Tumorigenesis