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Federal Register / Vol. 86, No. 40 / Wednesday, March 3, 2021 / Rules and Regulations
D. Methyl Bromide 1. Description Methyl bromide is a halogenated alkane and occurs as a gas. Methyl bromide has been used as a fumigant fungicide applied to soil before planting, to crops after harvest, to vehicles and buildings, and for other specialized purposes. Use of the chemical in the United States was phased out in 2005, except for specific critical use exemptions and quarantine and pre-shipment exemptions in accordance with the Montreal Protocol.
Critical use exemptions have included strawberry cultivation and production of dry cured pork. Synonyms for methyl bromide include bromomethane, monobromomethane, curafume, MethO-Gas, and Brom-O-Sol. Methyl bromide is expected to have moderate persistence in water due to its susceptibility to hydrolysis USEPA, 2021a.
2. Agency Findings The Agency is making a determination not to regulate methyl bromide with an NPDWR. Methyl bromide 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.

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a Adverse Health Effects The Agency finds that methyl bromide may have adverse effects on the health of persons. The limited number of studies investigating the oral toxicity of methyl bromide indicate that the route of administration influences the toxic effects observed USEPA, 2006c.
The forestomach of rats forestomachs are not present in humans appears to be the most sensitive target of methyl bromide when it is administered orally by gavage ATSDR, 1992. Acute and subchronic oral gavage studies in rats identified stomach lesions Kaneda et al., 1998, hyperemia excess blood Danse et al., 1984, and ulceration Boorman et al., 1986; Danse et al., 1984 of the forestomach. However, forestomach effects were not observed in rats and stomach effects were not observed in dogs that were chronically exposed to methyl bromide in the diet, potentially because methyl bromide degrades to other bromide compounds in the food Mertens, 1997. Decreases in food consumption, body weight, and body weight gain were noted in the chronic rat study when methyl bromide was administered in capsules Mertens, 1997.

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In a subchronic 13-week rat study Danse et al., 1984, a NOAEL of 1.4 mg/
kg/day a time weighted average, 57
days, of the 2 mg/kg/day dose group was selected in the EPA IRIS assessment based on severe hyperplasia of the stratified squamous epithelium in the forestomach, in the next highest dose group of 7.1 mg/kg/day USEPA, 1989.
In ATSDRs Toxicological Profile ATSDR, 1992, a lower dose of 0.4 mg/
kg/day is selected as the NOAEL
because mild focal hyperemia was observed at the 1.4 mg/kg/day dose level. It is worth noting that authors of this study reported neoplastic changes in the forestomach. However, EPA and others USEPA, 1985; Schatzow, 1984
re-evaluated the histological results, concluding that the lesions were hyperplasia and inflammation, not neoplasms. ATSDR notes that histological diagnosis of epithelial carcinomas in the presence of marked hyperplasia is difficult Wester and Kroes 1988; ATSDR 1992. Additionally, the hyperplasia of the forestomach observed after 13 weeks of exposure to bromomethane regressed when exposure ended Boorman et al. 1986;
ATSDR 1992.
EPA selected an OPP Human Health Risk Assessment from 2006 as the basis for developing the HRL for methyl bromide USEPA, 2006c. As described in the OPP document, the study was of chronic duration two years with four groups of male rats and four groups of female rats treated orally via encapsulated methyl bromide. In the OPP assessment USEPA, 2006c, Mertens 1997 was identified as the critical study and decreased body weight, decreased rate of body weight gain, and decreased food consumption were the critical effects in rats orally exposed to methyl bromide USEPA, 2006c. The NOAEL was 2.2 mg/kg/day and the LOAEL was 11.1 mg/kg/day.
The RfD derived in the 2006 OPP
Human Health Assessment is 0.022 mg/
kg/day, based on the point of departure POD of 2.2 mg/kg/day the NOAEL
and a combined uncertainty factor UF
of 100 for interspecies variability 10
and intraspecies variability 10. No benchmark dose modeling was performed.
Neurological effects reported after inhalation exposures have not been reported after oral exposures, indicating that route of exposure may influence the most sensitive adverse health endpoint USEPA, 1988.
Limited data are available regarding the developmental or reproductive toxicity of methyl bromide, especially via the oral route of exposure. ATSDR
1992 found no information on
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developmental effects in humans with methyl bromide exposure. An oral developmental toxicity study of methyl bromide in rats doses of 3, 10, or 30
mg/kg/day and rabbits doses of 1, 3, or 10 mg/kg/day found that there were no treatment-related adverse effects in fetuses of the treated groups of either species Kaneda et al., 1998. ATSDRs 1992 Toxicological Profile also did not identify any LOAELs for rats or rabbits in this study. In rats exposed to 30 mg/
kg/day, there was an increase in fetuses having 25 presacral vertebrae; however, ATSDR notes that there were no significant differences in the number of litters with this variation and the effect was not exposure-related ATSDR, 1992. No significant alterations in resorptions or fetal deaths, number of live fetuses, sex ratio, or fetal body weights were observed in rats and no alterations in the occurrence of external, visceral, or skeletal malformations or variations were observed in the rabbits.
Some inhalation studies reported no effects on development or reproduction, but other inhalation studies show adverse developmental effects. For example, Hardin et al. 1981 and Sikov et al. 1980 conducted studies in rats and rabbits and found no developmental effects, even when maternal toxicity was severe ATSDR, 1992. However, another inhalation study of rabbits found increased incidence of gallbladder agenesis, fused vertebrae, and decreased fetal body weights in offspring Breslin et al., 1990.
Decreased pup weights were noted in a multigeneration study in rats exposed to 30 ppm Enloe et al., 1986.
Reproductive effects were noted in intermediate-duration inhalation studies in rats and mice Eustis et al., 1988;
Kato et al., 1986, which indicated that the testes may undergo degeneration and atrophy at high exposure levels.
In the OPP HHRA for methyl bromide USEPA, 2006c, methyl bromide is classified as not likely to be carcinogenic to humans. In 2007, EPA
published a PPRTV report which stated that there is inadequate information to assess the carcinogenic potential of methyl bromide in humans USEPA, 2007a. The PPRTV assessment agrees with earlier National Toxicology Program NTP conclusions that the available data indicate that methyl bromide can cause genotoxic and/or mutagenic changes. The PPRTV
assessment states that the results in studies by Vogel and Nivard 1994 and Gansewendt et al. 1991 clearly indicate methyl bromide is distributed throughout the body and is capable of methylating DNA in vivo. However, the
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