title: Characterization of the LOAEL-to-NOAEL uncertainty factor for mild adverse effects from acute inhalation exposures.
abstract: This analysis was undertaken to reduce uncertainty in acute inhalation risk assessment for mild acute effects. Applying uncertainty factors (UFs) to the no-observed-adverse-effect level (NOAEL) is the primary approach used in threshold-based risk assessments. When a NOAEL is unavailable, a UF of 10 is often applied to a lowest-observed-adverse-effect level (LOAEL) to estimate the NOAEL. We evaluated the LOAEL-to-NOAEL relationship for mild acute inhalation toxicity for 215 data sets for 36 hazardous air pollutants. The LOAEL-to-NOAEL ratios were 2.0, 5.0, 6.3, and 10.0 for the 50th, 90th, 95th, and 99 th percentile, respectively. The 90% confidence interval for the 95th percentile was 5.0-7.5. Consequently, based on previous dose placement practice, the LOAEL-to-NOAEL UF of 6 would be protective for 95% of the responses, and a value of 10 would be protective of 99% of the responses. The ratio values were not associated with the size of the experimental group. There was little variability among species, particularly at the median. This analysis is reflective only of mild acute inhalation toxicity. For other exposure routes, exposure durations, or more severe toxicity, the distributions are likely to be different.
authors.affiliation: California Environmental Protection Agency, Office of Environmental Health Hazard Assessment, Oakland 94612, California. galexeef@oehha.ca.gov
authors.forename: George V
authors.initials: GV
authors.lastname: Alexeeff
authors.forename: Rachel
authors.initials: R
authors.lastname: Broadwin
authors.forename: Jane
authors.initials: J
authors.lastname: Liaw
authors.forename: Stanley V
authors.initials: SV
authors.lastname: Dawson
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D006224:Cricetinae; D004285:Dogs; D017408:Guidelines as Topic; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D019570:Inhalation Exposure / Q000706:statistics & numerical data*; D051379:Mice; D015233:Models, Statistical; D019055:No-Observed-Adverse-Effect Level; D016016:Proportional Hazards Models; D011817:Rabbits; D051381:Rats; D018570:Risk Assessment / Q000379:methods* / Q000706:statistics & numerical data; D018675:Toxicity Tests / Q000706:statistics & numerical data*; D035501:Uncertainty; D014481:United States
chemical_list: D000393:Air Pollutants