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Federal Register / Vol. 86, No. 40 / Wednesday, March 3, 2021 / Rules and Regulations seminiferous tubules, testicular atrophy, a large decrease in sperm count, and a reduction of sperm motility and/or viability, which contribute to a loss of fertility NTP, 1983; Bond et al., 1981;
Koida et al., 1995; Matsuura et al., 1995;
Kawashima et al., 1995. These data suggest that nitrobenzene is a malespecific reproductive toxicant USEPA, 2009.
Under the Guidelines for Carcinogen Risk Assessment USEPA, 2005, nitrobenzene is classified as likely to be carcinogenic to humans by any route of exposure USEPA, 2009. A
two-year inhalation cancer bioassay in rats and mice Cattley et al., 1994; CIIT, 1993 reported an increase in several tumor types in both species. However, the lack of available data, including a physiologically based biokinetic or model that might predict the impact of the intestinal metabolism on serum levels of nitrobenzene and its metabolites following oral exposures, precluded EPAs IRIS program from deriving an oral CSF USEPA, 2009.
Additionally, a metabolite of nitrobenzene, aniline, is classified as a probable human carcinogen B2
USEPA, 1988.
Nitrobenzene has been shown to be non-genotoxic in most studies and was classified as, at most, weakly genotoxic in the 2009 USEPA IRIS assessment ATSDR, 1990; USEPA, 2009.
Of the available animal studies with oral exposure to nitrobenzene, the 90day gavage study conducted by NTP
1983 is the most relevant study for deriving an RfD for nitrobenzene. This study used the longest exposure duration and multiple dose levels.
Benchmark dose software BMDS
version 1.4.1c; USEPA, 2007b was applied to estimate candidate PODs for deriving an RfD for nitrobenzene. Data for splenic congestion and increases in reticulocyte count and metHb concentration were modeled. The POD
derived from the male rat increased metHb data with a benchmark response BMR of 1 standard deviation SD was selected as the basis of the RfD see USEPA, 2009 for additional detail.
Therefore, the benchmark dose level BMDL used as the POD is a BMDL1SD
of 1.8 mg/kg/day.
In deriving the RfD, EPAs IRIS
program applied a composite UF of 1,000 to account for interspecies extrapolation 10, intraspecies variation 10, subchronic-to-chronic study extrapolation 3, and database deficiency 3 USEPA, 2009. Thus, the RfD calculated in the 2009 IRIS
assessment is 0.002 mg/kg/day. The overall confidence in the RfD was medium because the critical effect is
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supported by the overall database and is thought to be protective of reproductive and immunological effects observed at higher doses; however, there are no chronic or multigenerational reproductive/developmental oral studies available for nitrobenzene.
Because the critical effect in this study increased metHb in the adult rat is not specific to a sensitive subpopulation or lifestage, the general adult population was selected in deriving the HRL for regulatory determination.
EPA calculated an HRL for the noncancer effects of nitrobenzene of 10
mg/L rounded from 12.8 mg/L, based on the RfD of 0.002 mg/kg/day, using 2.5 L/
day drinking water ingestion, 80 kg body weight, and a 20% RSC factor.

all of which were in support of its preliminary determination not to regulate nitrobenzene. EPA agrees with the comments that are in support of the negative regulatory determination.

b Occurrence EPA has determined that nitrobenzene does not occur with a frequency and at levels of public health concern at PWSs based on the Agencys evaluation of available occurrence information. The primary occurrence data for nitrobenzene are nationally representative finished water monitoring data generated through EPAs UCMR 1 a.m. 20012003. UCMR
1 collected 33,576 finished water samples from 3,861 PWSs serving 226
million people for nitrobenzene and it was detected in only a small number of those samples 0.01% above the HRL
10 mg/L, which is the same as the MRL
10 mg/L.
Findings from the available ambient water data for nitrobenzene are consistent with the results in finished water. Ambient water data in NAWQA
show that nitrobenzene was not detected in any of the samples collected under any of the three monitoring cycles, while NWIS data show that nitrobenzene was detected in approximately 1% of samples.

2. Agency Findings
c Meaningful Opportunity The Agency has determined that regulation of nitrobenzene 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 1 data indicate that the estimated population exposed to nitrobenzene above the HRL
is 0.1%. The Agency finds that an NPDWR for nitrobenzene does not present a meaningful opportunity for health risk reduction.
d Summary of Public Comments on Nitrobenzene and Agency Responses EPA received several comments on the Agencys evaluation of nitrobenzene under section 1412b1A of SDWA,
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G. RDX
1. Description RDX is a nitrated triazine and is an explosive. The name RDX is an abbreviation of Royal Demolition eXplosive. The formal chemical name is hexahydro-1,3,5-trinitro-1,3,5triazine. RDX is expected to have a moderate to high likelihood of partitioning to water and low to moderate persistence in water USEPA, 2021a.

The Agency is making a determination not to regulate RDX with an NPDWR. RDX does not occur with a frequency and at levels of public health concern. As a result, the Agency finds that an NPDWR does not present a meaningful opportunity for health risk reduction.
a Adverse Health Effects The Agency finds that RDX may have adverse effects on the health of persons.
Available health effects assessments include an IRIS toxicological review USEPA, 2018e, and older assessments including an ATSDR toxicological profile ATSDR, 2012 and an OW
assessment published in the 1992
Drinking Water Health Advisory:
Munitions USEPA, 1992. The EPA
IRIS assessment 2018e presents an RfD
of 0.004 mg/kg/day based on convulsions as the critical effect observed in a subchronic study in F344
rats by Crouse et al. 2006. The POD for the derivation was a BMDL0.05 of 1.3
mg/kg/day derived using a pharmacokinetic model that identified the human equivalent dose HED based on arterial blood concentrations in the rats as the dose metric. A 300-fold UF
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.
Additionally, the EPA IRIS
assessment USEPA, 2018e classified data from the Lish et al. 1984 chronic study in B6C3F1 as providing suggestive evidence of carcinogenic potential following EPA USEPA, 2005
guidelines. The slope factor was derived from the lung and liver tumors doseresponse in the Lish et al. 1984 study.
The POD for the slope factor was the BMDL10 allometrically scaled to a HED

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