New York Codes, Rules and Regulations
Title 6 - DEPARTMENT OF ENVIRONMENTAL CONSERVATION
Chapter X - DIVISION OF WATER RESOURCES
Subchapter A - GENERAL
Article 2 - CLASSIFICATIONS AND STANDARDS OF QUALITY AND PURITY
Part 702 - Derivation and use of Standards and Guidance Values
Section 702.4 - Procedures for deriving standards and guidance values based on oncogenic effects

Universal Citation: 6 NY Comp Codes Rules and Regs § 702.4

Current through Register Vol. 46, No. 39, September 25, 2024

(a) Standards and guidance values based on oncogenic 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, tumor types and sites, 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 LED10, which is the 95 percent lower confidence limit on the dose associated with 10 percent excess risk for oncogenic effects adjusted for background risk. A different level of excess risk may be used if deemed more appropriate based on scientific evidence.

(2) The point-of-departure shall be estimated using a validated, biologically-based dose-response model. If such a model does not exist, the point-of-departure shall be estimated using a mathematical model (i.e., the multistage, probit, logistic, or Weibull model) that best describes the dose-response data within the range of observation. Statistical measures, including the Chi-squared goodness-of-fit test, shall be used to determine which model best describes the data.

(3) If the selected dose-response data are not adequately described by methods in paragraph (2) of this subdivision, an alternative point-of-departure (e.g., a NOEL or LOEL) shall be used.

(c) If the point-of-departure is derived from an animal study, the human equivalent dose (milligrams of substance per kilogram of body weight per day) at the point-of-departure shall be estimated by multiplying the animal-to-human body weight ratio raised to the 0.25 power by the animal dose in milligrams of substance per kilogram of body weight per day. An alternative trans-species conversion method may be used if deemed more appropriate based on scientific evidence.

(d) The standard or guidance value shall be derived by extrapolating from the point-of-departure to the human dose at the standard or guidance value.

(1) If a validated biologically-based dose-response model is used to estimate the point-of-departure, the standard or guidance value shall be based on the 95 percent lower confidence limit on the human dose corresponding to an excess lifetime cancer risk of one-in-one million and shall be estimated using the model. If such a model is not available or is not validated for humans, the extrapolation method from the point-of-departure to the human dose at the standard or guidance value shall depend on the results of a mode-of-action analysis.

(2) If data on mode-of-action are unavailable, or if the mode-of-action analysis provides evidence of linearity at low doses or does not provide unequivocal evidence of nonlinearity at low doses, the standard or guidance value shall be based on the 95 percent lower confidence limit on the human dose corresponding to an excess lifetime cancer risk of one-in-one million. The human dose at the standard or guidance value shall be estimated by multiplying the human equivalent dose at the point-of-departure derived according to paragraphs (b)(1) and (2) of this section by a factor equal to the risk level of one-in-one million divided by the risk level at the point-of-departure.

(3) If a mode-of-action analysis provides no evidence for linearity at low doses and provides unequivocal evidence of nonlinearity at low doses, the standard or guidance value shall be based on the human equivalent dose at the point-of-departure identified by the methods in subdivision (b) of this section divided by an uncertainty factor that will insure that the human dose at the standard or guidance value will be without appreciable risk to the human population, including children. The magnitude of this factor will generally range from 10 to 3,000. Factors that will be considered in determining the magnitude of the uncertainty factor shall include: the nature of the dose-response curve and the point-of-departure; the relative sensitivities of experimental animals and humans; the nature and extent of human variation, including age-dependent differences in sensitivity during a lifetime; and the data gaps in the toxicological database.

(e) Standards and guidance values based on the 95 percent lower confidence limit on the human dose corresponding to an excess lifetime cancer risk of one-in-one million shall be derived using age-specific body weights for a lifetime exposure period of 70 years if scientific evidence is sufficient to show that children may be more sensitive than adults to the oncogenic effect. If such evidence is not available, a body weight of 70 kilograms and a lifetime exposure period of 70 years shall be used.

(f) Standards and guidance values based on the human equivalent dose at the point-of-departure divided by an uncertainty factor shall allow no more than 20 percent of the human dose at the standard or guidance value 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 the oncogenic effect. If such evidence is not available, a body weight of 70 kilograms shall be used.

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