N.Y. Comp. Codes R. & Regs. tit. 6 § 702.5

Current through Register Vol. 46, No. 50, December 11, 2024

Section 702.5 - Procedures for deriving standards and guidance values based on nononcogenic effects

(a) Standards and guidance values based on nononcogenic effects shall be calculated using dose-response data from scientifically valid human or animal studies. Considering factors, including but not limited to route, duration and timing of exposure, species, strain, nature and severity of effects, pharmacokinetics, mode-of-action, study quality and statistical significance, the dose-response data deemed to be the most appropriate for evaluating potential human health risks at environmental exposures shall be used as the basis of the value.

(b) Standards and guidance values shall be based on the point-of-departure for the selected dose-response data.

(1) The point-of-departure shall be the no-observed-effect level (NOEL), expressed as a dose in milligrams of substance per kilogram of body weight per day. Where a valid NOEL is not available, a lowest-observed-effect level (LOEL) may be used.

(2) If neither a NOEL or a LOEL are available, an alternative point-of-departure, e.g., the 95 percent lower confidence limit on the dose associated with a specified percentage of excess risk (e.g., 10 percent) for a nononcogenic effect adjusted for background risk, may be used. The alternative point-of-departure shall be estimated using one of the mathematical models that are appropriate for analysis of dichotomous or continuous dose-response data (e.g., power, polynomial, or linear), and shall be the model that best describes the dose-response data within the range of experimental observation. Statistical measures, including the Chi-squared goodness-of-fit test, shall be used to determine which model best describes the data.

(c) The standard or guidance value shall be derived by extrapolating from the point-of-departure to the reference dose (RfD). The RfD shall be estimated by dividing the NOEL (or LOEL, or an alternative point-of-departure) by an uncertainty factor. The magnitude of this factor shall insure that exposures at or below the reference dose are without appreciable risk to the human population, including children, and will generally range from 10 to 3,000. It shall account for the following areas of uncertainty:

(1) LOEL to NOEL extrapolation (where necessary, to account for uncertainty where extrapolating from a LOEL to a NOEL);

(2) subchronic to chronic extrapolation (where necessary, to account for uncertainty where extrapolating from a less-than-chronic study NOEL (or LOEL, or other point-of-departure) to a chronic NOEL, LOEL, or other point-of-departure;

(3) animal to human extrapolation (where necessary, to account for uncertainty where extrapolating from experimental animals to humans);

(4) inter-human variability (where necessary, to account for variation in sensitivity among the human population, including special consideration of the potential sensitivity of children); and

(5) data gaps (where necessary, to account for areas of scientific uncertainty in the toxicological database).

(d) Standards and guidance values based on chronic toxic effects shall allow no more than 20 percent of the reference dose to come from drinking water and shall be derived using age-specific body weights for a childhood exposure period (18 years or less) if scientific evidence is sufficient to show that children may be more sensitive than adults to such effects. If such evidence is not available, a body weight of 70 kilograms shall be used.

(e) Standards and guidance values based on acute toxic effects shall allow 20 percent of the reference dose to come from drinking water and shall be derived using a child body weight of 10 kilograms. Alternative values for percentage of reference dose or for body weight may be used if deemed more appropriate based on scientific evidence.

N.Y. Comp. Codes R. & Regs. Tit. 6 § 702.5