Indiana Administrative Code › Title 327 - WATER POLLUTION CONTROL DIVISION › Article 2 - WATER QUALITY STANDARDS › Rule 1 - Water Quality Standards Applicable to All State Waters Except Waters of the State Within the Great Lakes System › Section 1-8.6 - Determination of concentration providing an acceptable degree of protection to public health for cancer

Current through July 10, 2024
Authority: 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:
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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
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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
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(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.