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Federal Register / Vol. 86, No. 40 / Wednesday, March 3, 2021 / Rules and Regulations
yielding a slope factor of 0.08 per mg/
kg/day.
In mice fed doses of 0 to 35 mg/kg/
day for 24 months in the Lish et al.
1984 study, there were dosedependent increases in adenomas or carcinomas of the lungs and liver in males and females USEPA, 2018e. The formulation used contained 3 to 10%
HMX, another munition ingredient. EPA
assessed the toxicity of HMX USEPA, 1988. No chronic-duration studies were available to evaluate the carcinogenicity of HMX USEPA, 1988. HMX is classified as Group D, or not classifiable as to human carcinogenicity USEPA, 1992; USEPA, 1988. In the Levine et al.
1983 RDX dietary exposure study with Fischer 344 rats, a statistically significant increase in the incidence of hepatocellular carcinomas was observed in males but not in females USEPA, 2018e. Although evidence of carcinogenicity included dosedependent increases in two experimental animal species, two sexes, and two systems liver and lungs, evidence supporting carcinogenicity in addition to the B6C3F1 mouse study was not robust; this factor contributed to the suggestive evidence of carcinogenic potential classification. EPA considered both the Lish et al. 1984 and Levine et al. 1983 studies to be suitable for doseresponse analysis because they were well conducted, using similar study designs with large numbers of animals at multiple dose levels USEPA, 2018e.
EPA 2018e concluded that insufficient information was available to evaluate male reproductive toxicity from experimental animals exposed to RDX.
In addition, EPA 2018e concluded that inadequate information was available to assess developmental effects from experimental animals exposed to RDX.
EPA selected the 2018 EPA IRIS
assessment to derive two HRLs for RDX:
The RfD-derived HRL based on Crouse et al., 2006 and the oral cancer slope factor-derived HRL based on Lish et al., 1984. EPA has generally derived HRLs for possible or Group C carcinogens using the RfD approach in past Regulatory Determinations. However, for RDX, EPA decided to show both an RfD-derived and oral-cancer-slopefactor-derived HRL since the mode of action for liver tumors is unknown and the 1 106 cancer risk level provides a more health protective HRL to evaluate the occurrence information.
The RfD-derived HRL for RDX was calculated using the RfD of 0.004 mg/kg/
day based on a subchronic study in F
344 rats by Crouse et al. 2006 with convulsions as the critical effect USEPA, 2018e. The point of departure for the RfD calculation was a human
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equivalent BMDL0.05 of 1.3 mg/kg/day.
The HED was derived using a pharmacokinetic model based on arterial blood concentrations in the rats as the dose metric. A 300-fold uncertainty factor 3 for extrapolation from animals to humans, 10 for interindividual differences in human susceptibility, and 10 for uncertainty in the database was applied in determination of the RfD. EPA
calculated a RfD-derived HRL of 30 mg/
L rounded from 25.6 mg/L, for the noncancer effects of RDX based on the RfD of 0.004 mg/kg/day, using 2.5 L/day drinking water ingestion, 80 kg body weight, and a 20% RSC factor.
The oral-cancer-slope-factor-derived HRL for RDX was also based on values presented in the 2018 EPA IRIS
assessment. The slope factor is derived from the dose-response for lung and liver tumors in the Lish et al. 1984
study, with elimination of the data for the high dose group due to high mortality. The point of departure for the slope factor of 0.08 mg/kg/day-1 was the BMDL10 which was allometrically scaled to a HED. EPA calculated an oral cancer slope factor-derived HRL of 0.4
mg/L for RDX based on the cancer slope factor of 0.08 mg/kg/day-1, using 2.5
L/day drinking water ingestion, 80 kg body weight, and a 1 in a million cancer risk level.
EPAs USEPA, 2018e derivation of an oral slope factor for cancer is in accordance with the Guidelines for Carcinogen Risk Assessment USEPA, 2005 while RDX is classified as having suggestive evidence of carcinogenic potential. Specifically, the guidelines state when the evidence includes a well-conducted study, quantitative analyses may be useful for some purposes, for example, providing a sense of the magnitude and uncertainty of potential risks, ranking potential hazards, or setting research priorities USEPA, 2005. The EPA IRIS
assessment concluded that the database for RDX contains well-conducted carcinogenicity studies Lish et al., 1984; Levine et al., 1983 suitable for dose response and that the quantitative analysis may be useful for providing a sense of the magnitude and uncertainty of potential carcinogenic risk USEPA, 2018e. Therefore, EPA felt it was important to evaluate the occurrence information against both the RfDderived HRL and the oral cancer slope factor-derived HRL.
b Occurrence EPA has determined that RDX does not occur with a frequency and at levels of public health concern at PWSs based on the Agencys evaluation of available
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occurrence information. The primary data for RDX are nationally representative drinking water monitoring data generated through EPAs UCMR 2 AM 20082010. UCMR
2 collected 32,150 finished water samples from 4,139 PWSs serving 229
million people for RDX and it was detected in only a small number of those samples 0.01% at or above the MRL. The detections occurred in three large surface water systems; the maximum detected concentration of RDX was 1.1 mg/L. The MRL is 1 mg/L, which is about 2.5 times higher than the oral cancer slope factor-derived HRL
0.4 mg/L. The RfD-derived HRL 30 mg/
L is 30 times higher than the MRL and 75 times higher than the cancer slope factor-derived HRL.
Findings from the available ambient water data for RDX in ambient water, available from NWIS, show that RDX
was detected in approximately 46% of samples and at approximately 29% of sites; RDX data are not available from the NAWQA program.
c Meaningful Opportunity The Agency has determined that regulation of RDX does not present a meaningful opportunity for health risk reduction for persons served by PWSs based on the estimated exposed populations, including sensitive populations. UCMR 2 findings indicate that the estimated population exposed to RDX at or above the MRL is 0.04%.
There were no detections greater than the non-cancer HRL 30 mg/L or the one-half the non-cancer HRL 15 mg/L.
Because the MRL of 1 mg/L is higher than the cancer HRL of 0.4 mg/L, the population exposed relative to the cancer HRL and 12 the cancer HRL is not presented here. As a result, the Agency finds that an NPDWR for RDX
does not present a meaningful opportunity for health risk reduction.
Based on the small number of samples measured at or marginally above the MRL, EPA does not believe that there would be enough occurrence in the narrow range between the HRL and the MRL to change the meaningful opportunity determination.
d Summary of Public Comments on RDX and Agency Responses EPA received several comments on the Agencys evaluation of RDX under section 1412b1A of SDWA, all of which were in support of its preliminary determination not to regulate RDX. EPA agrees with the comments that are in support of the negative regulatory determination.

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