The use of benchmark dose methodology with acute inhalation lethality data.
Benchmark dose methodology has been proposed as a refinement to the no observed adverse effect level (NOAEL) methods currently used for health risk assessments. We compared log-normal probit and quantal Weibull benchmark concentration (BMC) estimates using 1, 5, and 10% response incidences with inhalation toxicity NOAELs and LOAELs from 120 acute lethality data sets. These studies yielded relatively steep dose-response slopes, which in turn influenced the suitability of selecting response incidences. The mean magnitude of difference between the 95% lower confidence limits (LCLs) for 1, 5, or 10% BMCs and corresponding NOAELs was less than twofold using the probit model and less than fourfold using the Weibull model. BMC estimates at the 10% response exceeded the observed LOAEL in some cases. Maximum likelihood estimates for doses with 1, 5, or 10% responses frequently exceeded LOAELs. The probit model repeatedly gave a better fit for the data compared with the Weibull model, resulting in improved goodness of fit tests and reduced 95% confidence intervals. The 95% LCL appears to be necessary at the 1, 5, or 10% response levels in order to safely estimate a concentration below that resulting in a LOAEL.
Fowles
J R
JR
California Environmental Protection Agency, Office of Environmental Health Hazard Assessment, Cal/EPA, 1515 Clay Street, 16th Floor, Oakland, California 94612, USA. jeff.fowles@esr.cri.nz
Alexeeff
G V
GV
Dodge
D
D
D000336:Aerosols / Q000008:administration & dosage / Q000633:toxicity*; D000465:Algorithms; D000818:Animals; D006224:Cricetinae; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011817:Rabbits; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity; D014116:Toxicology / Q000592:standards*
D000336:Aerosols