New method for determining allowable daily intakes

Journal Article · Mon Oct 01 00:00:00 EDT 1984 · Fundam. Appl. Toxicol.; (United States)

DOI:https://doi.org/10.1016/0272-0590(84)90107-6· OSTI ID:5762443

Crump, K S

The usual method for establishing allowable daily intake (ADI) for a chemical involves determining a no-observed-effect level (NOEL) and applying a safety factor. Even though this method has been used for many years, there appear to be no general guidelines or rules for defining a NOEL. The determination of a NOEL is particularly uncertain for lesions which occur naturally in untreated animals. NOELs also have shortcomings in that smaller experiments tend to give larger values (this should be reversed because larger experiments can provide greater evidence of safety) and that the steepness of the dose response in the dose range where effects occur plays little or no role in the determination of a NOEL. This paper proposes and illustrates the use of a benchmark dose (BD) as an alternative to a NOEL. A BD is a statistical lower confidence limit to a dose producing some predetermined increase in response rate such as 0.01 or 0.1. The BD is calculated using a mathematical dose-response model. This approach makes appropriate use of sample size and the shape of the dose-response curve. The BD normally will not depend strongly upon the mathematical model used because the method does not involve extrapolation far below the experimental range. Thus the method sidesteps much of the model dependency often associated with extrapolation of carcinogenicity data to low doses. The method can be applied to either quantal data in which only the presence or absence of an effect is recorded, or continuous data in which the severity of the effect is also noted.

• Research Organization: K.S. Crump and Co., Inc., Ruston, LA
• OSTI ID: 5762443
• Journal Information: Fundam. Appl. Toxicol.; (United States), Vol. 4:5
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
XENOBIOTICS
DOSE LIMITS
INTAKE
ANIMALS
CARCINOGENS
DOSE-RESPONSE RELATIONSHIPS
EXTRAPOLATION
INJURIES
MATHEMATICAL MODELS
MAXIMUM PERMISSIBLE EXPOSURE
RISK ASSESSMENT
NUMERICAL SOLUTION
SAFETY STANDARDS
STANDARDS
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)