An approach for modeling noncancer dose responses with an emphasis on uncertainty.
This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors used in setting RfDs. The approach requires generally available toxicological estimates such as No-Observed-Adverse-Effect Levels (NOAELs) or Benchmark Doses and doses at which adverse effects are observed in 50% of the test animals (ED50s). In this approach, Monte Carlo analysis is used to characterize the uncertainty in the dose response slope based on the range and magnitude of the key sources of uncertainty in setting protective doses. The method does not require information on the shape of the dose response curve for specific chemicals, but is amenable to the inclusion of such data. The approach is applied to four compounds to produce estimates of response rates for dose rates greater than the RfD.
Price
P S
PS
McLaren/Hart-ChemRisk, Portland, Maine 04102, USA.
Keenan
R E
RE
Swartout
J C
JC
Gillis
C A
CA
Carlson-Lynch
H
H
Dourson
M L
ML
D000081:Acetamides / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004785:Environmental Pollutants / Q000008:administration & dosage* / Q000633:toxicity*; D006581:Hexachlorobenzene / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D016014:Linear Models; D008433:Mathematics; D008954:Models, Biological; D009010:Monte Carlo Method; D019055:No-Observed-Adverse-Effect Level; D010269:Paraquat / Q000008:administration & dosage / Q000633:toxicity; D010416:Pentachlorophenol / Q000008:administration & dosage / Q000633:toxicity; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000592:standards; D011336:Probability; D018570:Risk Assessment
D000081:Acetamides; D004785:Environmental Pollutants; D004364:Pharmaceutical Preparations; C000188:alachlor; D006581:Hexachlorobenzene; D010416:Pentachlorophenol; D010269:Paraquat