Section 327 IAC 2-1-8.6 - Determination of concentration providing an acceptable degree of protection to public health for cancerAuthority: IC 13-1-3-7; IC 13-7-7-5
Affected: IC 13-1-3-7; IC 13-7-7-5
Sec. 8.6.
(a) The concentration providing an acceptable degree of protection to public health for cancer shall be derived as provided in subsection (b)(1). For carcinogens that are assumed to cause cancer by a nonthreshold mechanism, a greater degree of protection than that derived in subsection (b)(1) may be proposed where this greater protection is achievable through utilization of control measures already in place.(b) Initially, any chemical for which at least one (1) published mammalian carcinogenicity study of suitable quality demonstrates an association between exposure to the chemical and a statistically or biologically significant increase in the incidence of malignant or benign tumors shall be considered a carcinogen. With respect to "suitable quality," the only type of carcinogenicity study which will be automatically excluded from consideration as sole evidence of the carcinogenic properties of a particular chemical will be studies in which the tested chemical was administered via an injection route of exposure and an increase in malignant or benign tumors was produced only at the site of injection. Not included in this category are studies in which an injection dosing was administered intratracheally or by gavage. The commissioner shall reevaluate the carcinogenic potential of substances when new data of suitable quality become available. (1) A water concentration of the carcinogen shall be derived from human epidemiological data or from appropriate animal research data using the following formula: Click here to view
Where: C = concentration of the carcinogen (mg/l)
D = dose derived in clause (A), (B), or (C) (mg/kg/day)
Wh = seventy (70) kilograms, weight of an average human
WC = daily water consumption (0.01 liters per day for surface water not protected for drinking water supply; 2.0 liters per day for surface waters protected for drinking water supply)
F = sixty-five ten-thousandths (0.0065) kilograms per day, daily fish consumption
BCF = bioconcentration factor in Click here to view as determined in section 8.7 of this rule
(A) The dose (D) may be derived from appropriate human epidemiological data on a case-by-case basis by the commissioner.(B) Whenever appropriate human epidemiological data are not available, a nonthreshold mechanism shall be assumed for carcinogens which have not been adequately demonstrated to cause cancer by a threshold mechanism. The dose (D) shall be the concentration estimated to cause one (1) additional cancer over the background rate in one hundred thousand (100,000) individuals exposed to that concentration calculated using the following method: (i) All carcinogenesis bioassay data are reviewed and data of appropriate quality are used for the quantitative risk estimations. The data are fitted into the multistage model using the computer model GLOBAL 82 developed by Howe and Crump (1982). The upper ninety-five percent (95%) confidence limit on risk at the one (1) in one hundred (100) risk level is divided by the maximum likelihood dose at the same level of risk which determines the slope, q1*. This is taken as an upper bound of the potency of the chemical in inducing cancer at low doses. Whenever the multistage model does not fit the data, as determined by the Chi-square goodness of fit statistical test, the model is refitted to the data omitting the highest dose. This is continued until an acceptable fit is determined as described in the U.S. EPA 1980 water quality criteria documents (45 Fed. Reg. 79316-79379). If a single study in which a chemical induces more than one (1) type of tumor is available, then the response for the tumor type predicting the highest estimate of q1* is generally used for the risk assessment. If two (2) or more studies of equal quality are available, but vary in any of the following: species, strain, sex, or tumor type, then the data set giving the highest estimate of q1* is generally used for the risk assessment. If two (2) or more studies exist which are identical regarding species, strain, sex, tumor type, and are of equal quality, then the geometric mean of the q1* values from these data sets is used.(ii) The dose corresponding to an estimated one (1) additional cancer in one hundred thousand (100,000) exposed test organisms is determined by dividing 10-5 by the value for q1*.(iii) A species sensitivity factor is used to account for differences between test species and man. It is assumed that milligrams per surface area per day is an equivalent dose between species. The value may be calculated by dividing the average weight of a human seventy (70) kilograms by the weight of the test species and taking the cube root of this value; the slope q1* is multiplied by this factor. However, if adequate pharmacokinetic and metabolism studies are available, this data may be factored into the adjustment for species differences on a case-by-case basis.(iv) All doses are adjusted to give a lifetime average daily dose. If dosing was only for a fraction of a lifetime, then the total dose is averaged over the entire life span.(v) If the duration of experiment (Le) is less than the natural life span of the test animal (L), the slope, q1*, is multiplied by the factor Click here to view
(C) Whenever appropriate human epidemiological data are not available, and the preponderance of data suggests that the chemical causes cancer by a threshold mechanism and does not interact with DNA, the dose (D) for chemicals shall be calculated from animal research data by applying a safety factor to an appropriate toxicity end point. (i) The appropriate toxicity end point shall be determined by the commissioner on a case-by-case basis.(ii) The safety factor shall be determined by the commissioner based on an evaluation of appropriate toxicological and pharmacological considerations including, mechanism of carcinogenesis, number and type of tumors induced, the spontaneous incidence of tumors, the number of animal species tested and affected, metabolic considerations, epidemiologic observation on exposed humans, extent of the data supporting a nongenetic mechanism, and other pertinent information.(iii) A species sensitivity factor may be used to account for differences between test species and man. (2) On the basis of available information, the concentration providing an acceptable degree of protection to public health for cancer is evaluated as to whether it is consistent with sound scientific judgment. If not, the commissioner will direct the evaluation of appropriate modifications of these procedures.Water Pollution Control Board; 327 IAC 2-1-8.6; filed Feb 1, 1990, 4:30 p.m.: 13 IR 1038; errata filed Jul 6, 1990, 5:00 p.m.: 13 IR 2004