[Federal Register Volume 60, Number 76 (Thursday, April 20, 1995)]
[Proposed Rules]
[Pages 19702-19708]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-9782]



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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 372

[OPPTS-400092; FRL-4946-2]


Monosodium Methanearsonate and Disodium Methanearsonate; Toxic 
Chemical Release Reporting; Community Right-to-Know

AGENCY: Environmental Protection Agency (EPA).

ACTION: Denial of petition.

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SUMMARY: EPA is denying a petition to delist monosodium methanearsonate 
(MSMA, CAS No. 2163-80-6) and disodium methanearsonate (DSMA, CAS No. 
144-21-8) from the reporting requirements under section 313 of the 
Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA). 
This action is based on EPA's conclusion that neither monosodium 
methanearsonate or disodium methanearsonate meet the deletion criteria 
of EPCRA section 313(d)(3). Specifically, EPA is denying this petition 
because: (1) Monosodium methanearsonate and disodium methanearsonate 
are known to cause toxic effects in experimental animals as a result of 
chronic exposure to either of these substances; and (2) monosodium 
methanearsonate and disodium methanearsonate can reasonably be 
anticipated to cause cancer in humans.

FOR FURTHER INFORMATION CONTACT: Maria J. Doa, Petitions Coordinator, 
202-260-9592, for specific information regarding this document. For 
further information on EPCRA section 313, contact the Emergency 
Planning and Community Right-to-Know Information Hotline, Environmental 
Protection Agency, Mail Stop 5101, 401 M St., SW., Washington, DC 
20460, Toll free: 800-535-0202, Toll free TDD: 800-553-7672.

SUPPLEMENTARY INFORMATION:

I. Introduction

A. Statutory Authority

    This action is issued under sections 313(d) and (e)(1) of the 
Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA), 42 
U.S.C. 11023. EPCRA is also referred to as Title III of the Superfund 
Amendments and Reauthorization Act (SARA) of 1986 (Pub. L. 99-499).

B. Background

    Section 313 of EPCRA requires certain facilities manufacturing, 
processing, or otherwise using listed toxic chemicals to report their 
environmental releases of such chemicals annually. Beginning with the 
1991 reporting year, such facilities also must report pollution 
prevention and recycling data for such chemicals, pursuant to section 
6607 of the Pollution Prevention Act of 1990 (PPA), 42 U.S.C. 13106. 
Section 313 established an initial list of toxic chemicals that was 
comprised of more than 300 chemicals and 20 chemical categories. 
Section 313(d) authorizes EPA to add or delete chemicals from the list, 
and sets forth criteria for these actions. EPA has added and deleted 
chemicals from the original statutory list. Under section 313(e), any 
person may petition EPA to add chemicals to or delete chemicals from 
the list. EPA must respond to petitions within 180 days, either by 
initiating a rulemaking or by publishing an explanation of why the 
petition is denied.
    EPA issued a statement of petition policy and guidance in the 
Federal Register of February 4, 1987 (52 FR 3479), to provide guidance 
regarding the recommended content and format for submitting petitions. 
On May 23, 1991 (56 FR 23703), EPA issued guidance regarding the 
recommended content of petitions to delete individual members of the 
section 313 metal compound categories. EPA has also published a 
statement clarifying its interpretation of the section 313(d)(2) 
criteria for adding and deleting chemical substances from the section 
313 list (59 FR 61439, November 30, 1994).

II. Description of Petition and Relevant Regulations

    On October 18, 1994, EPA received a petition from the ISK 
Biosciences Corporation to remove monosodium methanearsonate (MSMA) and 
disodium methanearsonate (DSMA) from the list of toxic chemicals 
subject to the requirements of section 313 of the Emergency Planning 
and Community Right-to-Know Act of 1986 (EPCRA). Specifically, the 
petition requests that MSMA and DSMA be excluded from the arsenic 
compounds category which is subject to annual release reporting 
requirements under EPCRA section 313. The petitioner contends that MSMA 
and DSMA should be deleted from the EPCRA section 313 arsenic compounds 
category because, in their opinion, the available data show that 
neither of these substances meet the criteria for inclusion on the list 
of EPCRA section 313 chemicals. The petitioner did not provide EPA with 
any of the studies cited in the petition.
    MSMA and DSMA are organic arsenicals. EPA regulates arsenic and 
certain arsenic compounds under the Clean Air Act (CAA), Clean Water 
Act (CWA), Comprehensive Environmental Response, Compensation, and 
Liability Act (CERCLA), Federal Insecticide, Fungicide, and Rodenticide 
Act (FIFRA), Resource Conservation and Recovery Act (RCRA), Safe 
Drinking Water Act (SDWA), and EPCRA. Arsenic emissions from smelters 
and other facilities are regulated under the CAA. Under the CWA, 
guidelines have been established controlling the environmental release 
of arsenic compounds for certain industrial categories. Reportable 
quantities have been established under CERCLA and CWA for arsenic and 
certain arsenic compounds. Under RCRA, EPA regulates arsenic as a 
hazardous constituent of waste. The SDWA limits arsenic in drinking 
water to a maximum level of 0.05 milligrams/liter (mg/L). EPA and the 
National Toxicology Program have classified inorganic arsenicals, 
including arsenate, as known human carcinogens.

III. EPA's Technical Review of Monosodium Methanearsonate (MSMA) 
and Disodium Methanearsonate (DSMA)

    The technical review of the petition to delete MSMA and DSMA 
included an analysis of the chemistry, health, ecological and 
environmental fate data known for these substances and for 
methanearsonic acid (MAA), the un-ionized form of MSMA and DSMA. From a 
human health standpoint, MSMA and DSMA will exist largely as MAA (their 
un-ionized form) under acidic conditions, such as those found in the 
gastrointestinal tract. Also, following absorption into the systemic 
circulation, MSMA, DSMA, and MAA will exist in an identical ionized 
form at the physiological pH of 7.4, regardless of their route of 
administration. EPA and the ISK Biosciences Corporation (as indicated 
in their petition) believe, therefore, that mammalian toxicity data on 
MAA should be suitable to assess the toxicity of MSMA and DSMA in cases 
where such data on the latter two substances are not available.

A. Chemistry

    Monosodium methanearsonate (CH4AsO3.Na; CAS No. 2163-80-
6), also known as MSMA, and disodium methanearsonate 
(CH3AsO3.2Na; CAS No. 144-21-8), also known as DSMA, are the 
monosodium and disodium salts, respectively, of methanearsonic acid 
(also known as MAA). MSMA, DSMA, and MAA are often refered to as 
organic arsenicals, because they each contain a methyl (-CH3) 
group. Both MSMA and DSMA are highly water soluble crystalline solids, 
and are used as herbicides for the postemergent control of grassy weeds 
in cotton, sugarcane, nonbearing orchards, citrus groves, lawns, turf, 
and in noncrop areas. The predominant use of MSMA and DSMA is for 
postemergent control of Johnsongrass and other grassy weeds prior to 
planting cotton.

B. Toxicological Evaluation

    Information on the health and environmental effects of MSMA, DSMA, 
and MAA were obtained from the following sources: a 1993 Agency for 
Toxic Substances and Disease Registry [[Page 19704]] document entitled 
Toxicological Profile for Arsenic (Update) (Refs. 2, 15, and 30); a 
1984 EPA document entitled Health Assessment Document for Arsenic (Ref. 
7); a 1994 National Toxicology Program document entitled Seventh Annual 
Report on Carcinogens: 1994 Summary (Ref. 32); studies obtained from 
EPA's Office of Pesticide Programs (Ref. 8, 10, 12-14, 16 and 19-24); 
and studies found in the literature (Refs. 1, 3-6, 9, 11, 17, 18, 25, 
26, 28, 29, and 31). Specifically, toxicological and related data on 
MSMA, DSMA, and MAA (the un-ionized or free acid form of MSMA and DSMA) 
were reviewed for evidence indicating: (1) Bioavailability and 
metabolism to inorganic arsenic; (2) acute toxicity; (3) chronic 
toxicity; (4) carcinogenicity; and (5) ecotoxicity.
    1. Bioavailability and metabolism. Shah and co-workers investigated 
the absorption of MSMA and DSMA from the skin of young and adult rats 
(Ref. 1). Both substances were very poorly absorbed through the skin of 
all animals tested, particularly in the younger animals. No human 
studies pertaining to the dermal absorption of MSMA and DSMA were 
found. However, human and animal studies involving dermal exposure to 
organic arsenicals closely related to MSMA and DSMA indicate that these 
substances are poorly absorbed from the skin (Ref. 2).
    Shariatpanahi and Anderson found that MSMA is readily absorbed from 
the gastrointestinal tract following oral administration of the 
substance to sheep and goats (Ref. 3). These investigators observed 
that 90 percent of the arsenic content of orally administered MSMA was 
excreted in the urine of test animals within 120 hours of 
administration. Small amounts were excreted in the feces. Arsenic 
accumulation in the tissues was low. It is noteworthy to point out that 
metabolism of MSMA to other forms of arsenic (e.g., inorganic) was not 
studied in this investigation, and only total arsenic concentrations 
were determined. Specific assays for MSMA or other specific arsenicals 
were not used. The results of this study were consistent with the 
results of another study, which investigated the absorption, 
distribution and elimination of MSMA in New Zealand white rabbits 
following multiple oral doses of the substance (Ref. 4).
    A 1991 EPA study investigated the absorption, distribution, and 
elimination of radiolabeled MSMA ([14C-methyl]MSMA) in rats (Ref. 
8). Four groups of rats were used in this study. Each group consisted 
of male and female animals. One group received a single oral dose of 
[14C-methyl]MSMA at 5 milligrams per kilogram (mg/kg), while 
another group received a single oral dose of 200 mg/kg. A third group 
received a single oral dose of MSMA at 5 mg/kg every day for 14 
consecutive days, followed by a single oral dose of [14C-
methyl]MSMA. A fourth group received a single oral dose of MSMA at 5 
mg/kg every day for 14 consecutive days, followed by a single 
intravenous dose of [14C-methyl]MSMA at 5 mg/kg or a single oral 
dose of [14C-methyl]MSMA at 5 mg/kg. In each of the test groups, 
the majority (79.7 to 97.4 percent) of administered [14C-
methyl]MSMA was excreted unchanged in the urine and feces within 7 days 
following dosing. Radiolabeled carbon dioxide (14CO2) was 
detected in all treated groups, and accounted for less than 0.5 percent 
of administered [14C-methyl]MSMA. An unidentified metabolite, 
which accounted for 1.8 to 6.7 percent of administered [14C-
methyl]MSMA, was detected in the urine and feces of all test groups 
except the group receiving 200 mg/kg [14C-methyl]MSMA orally. 
Another unidentified metabolite, accounting for 0.7 percent of 
administered [14C-methyl]MSMA was found in only one of the test 
groups.
    Buchet, et al., investigated the oral absorption and metabolism of 
MSMA in humans (Ref. 9). In this study four adult males were 
administered MSMA in a single oral dose equivalent to 500 micrograms of 
arsenic. The MSMA was well absorbed, and nearly 70 percent of the dose 
was excreted unchanged in the urine within 24 hours, while a small 
percentage was excreted in the urine as cacodylic acid (dimethylarsonic 
acid). Within 96 hours, 78.3 percent of the MSMA dose was excreted in 
the urine unchanged and approximately 13 percent was excreted in the 
urine as cacodylic acid. No inorganic arsenic metabolites were 
identified (Ref. 9).
    Stevens and co-workers investigated the toxicity of DSMA in rats 
and mice exposed to the substance at aerosolized doses of 6.1 mg/L (for 
the rats) and 6.9 mg/L (for the mice) for 2 hours (Ref. 5). Total 
arsenic levels from body fluids or tissues were not determined, but the 
authors believed that some absorption of DSMA occurred from the lung.
    2. Acute toxicity. Several rat oral median lethal dose (LD50) 
values for MSMA and DSMA were found in the literature. For DSMA, the 
rat oral LD50 values, in mg/kg, are (male, female): 2,005, 1,842 
(Ref. 10); and 928, 821 (Ref. 11). For MSMA, the rat oral LD50 
values are 1,105 and 1,059 mg/kg for males and females respectively 
(Ref. 11). These data are consistent with rat median lethal dose data 
provided by the petitioner.
    Neither DSMA or MSMA produced significant toxicity in rabbits when 
applied dermally at a dose of 2,000 mg/kg for 24 hours (Refs. 12 and 
13). In the MSMA- treated group, however, there was evidence of 
decreased muscle tone noted in approximately 50 percent of the animals 
on observation days 5 through 9 (Ref. 13). By observation day 10, 
muscle tone was normal in all treated animals.
    In a study investigating the acute inhalation toxicology of DSMA, 
mice and rats were placed in chambers and were exposed for 2-hours to 
experimental atmospheres containing DSMA in concentrations of at least 
8.6 mg/L (Ref. 5). The animals were observed to have respiratory 
distress during the 2-hour exposure period, but recovered rapidly after 
removal from exposure. Respiratory irritation was the main 
toxicological effect observed. No mortality occurred in either species. 
These results are consistent with those of a similar DSMA inhalation 
study (Ref. 14). In the latter study, rats were exposed to experimental 
atmospheres of 6.0 mg/L DSMA for 4 hours. No deaths were noted during 
the 14-day post-exposure observation period. Clinical signs noted on 
the first day post-exposure included body weight loss and respiratory 
irritation. Lung discoloration in 40 percent of the animals was also 
noted (Ref. 14).
    3. Chronic toxicity. Numerous studies investigating the chronic 
toxicity of inorganic arsenicals have been conducted. Relatively few 
studies, however, have investigated the potential for chronic toxicity 
of organic arsenicals such as MSMA, DSMA, and MAA. The limited amount 
of published mammalian toxicity data on these substances have been 
summarized (Ref. 15). In addition, the petitioner summarized 
unpublished chronic toxicity data that are available from EPA's Office 
of Pesticide Programs. Some of these studies will be briefly discussed 
here.
    In a study investigating the health effects resulting from chronic 
administration of MAA, four groups of rats (each group consisting of 60 
males and 60 females) were fed diets containing 0 (the control group), 
50, 400, and 1,300 parts per million (ppm) of MAA for 104 weeks (Ref. 
16). Mortality was significantly increased in animals fed diets 
containing 1,300 ppm MAA. Because of this increased mortality, the 
1,300 ppm concentration was reduced to 1,000 ppm during week 53, and to 
800 ppm at week 60. Animals in this group had acute gastrointestinal 
inflammation, ulceration and perforation of the large intestines, and 
[[Page 19705]] evidence of acute or chronic peritonitis. These 
observations were less evident in animals receiving diets containing 
400 ppm MAA. A reduction in the weight of the thyroid glands was noted 
in female rats receiving the 1,300 ppm and 400 ppm MAA diets, and in 
male rats receiving 400 ppm MAA. Thickening of the thyroid follicular 
epithelium was noted in both sexes receiving the 1,300 and 400 ppm MAA 
diets. An increased incidence of parathyroid adenomas may have occurred 
in male rats receiving the 1,300 and 400 ppm MAA diets. This 
observation is discussed in greater detail in unit III.B.4 below.
    Jaghabir and co-workers investigated the health effects of low dose 
MSMA exposure in white rabbits (Ref. 17). Three groups of rabbits were 
used in this study. The first group consisted of four rabbits, which 
were administered MSMA orally once a day for 40 days at a dose of 5 mg/
kg. The second group consisted of two animals, which were administered 
MSMA at a dose of 10 mg/kg orally for 40 days. The third group (also 
consisting of two animals) was similarly administered MSMA at a dose of 
20 mg/kg. A control group of two animals was also used. All animals 
were euthanized and examined at the end of the 40-day test period. 
Post-mortem examination revealed distension and hyperemia of the 
digestive tract, intestinal wall fragility, enlargement of the kidneys, 
and intense peripheral hyperemia of the livers of all animals 
administered MSMA. Histopathological findings revealed hepatic cellular 
degeneration, periportal inflammation, renal tubular nephrosis, 
interstitial nephritis and vascular hyperemia. These observations are 
consistent with the observations of similar investigations cited in the 
study (Ref. 17), and indicate that low dose exposure to MSMA can result 
in tissue damage.
    Results from several studies suggest that MSMA and DSMA may cause 
developmental and reproductive toxicity. In an investigation reported 
by Prukop and Savage (Ref. 18) it was observed that mice administered 
MSMA at doses of either 11.9 or 119 mg/kg orally three times a week for 
10 weeks had decreased reproductive capabilities (males) and altered 
reproductive behavior (females). In another study, groups of beagle 
dogs were administered MAA at 0 (control), 2.5, 8 or 40 mg/kg/day for 1 
week, followed by administration of 0 (control animals), 2, 8, or 35 
mg/kg/day for an additional 51 weeks (Ref. 19). Decreased body weight 
gain occurred in male dogs that received the 35 mg/kg/day dose, and in 
females that received the 8 or 35 mg/kg/day doses. The incidence of 
female animals showing no corpora lutea were increased in the 35 mg/kg/
day animal test group when compared to control animals (Ref. 19).
    In another study, groups of inseminated New Zealand white rabbits 
were administered MAA orally at doses of 0 (control animals), 1, 3, 7, 
and 12 mg/kg/day during days 7 thru 19 of gestation (Ref. 20). Maternal 
toxicity at 12 mg/kg/day was characterized by abortion and decreases in 
mean absolute body weight, body weight gain, and food consumption. 
Decreases in body weight gain and food consumption were also noted in 
the 7 mg/kg/day test group. An increased incidence of skeletal 
variations was noted in the offspring of animals administered MAA at 12 
mg/kg/day. These skeletal variations consisited of increased numbers of 
ribs and thoracic and lumbar vertebrae (Ref. 20).
    In a multigeneration toxicity study, groups of male rats were fed 
MAA at doses of 0 (control group), 5.8, 17.8, or 63.5 mg/kg/day, and 
groups of female rats were fed 0 (control group), 7.5, 22.5, and 77.6 
mg/kg/day for 14 weeks. Animals were mated, and mated females continued 
to receive MAA throughout gestation and lactation periods. Among other 
toxic effects noted in the 63.5 (males) and 77.6 (females) mg/kg/day 
dose groups, decreased pregnancy rates, male fertility rates, and 
decreased weights of the prostate and testes also occurred for 
parenteral generations F0 and F1 (Ref. 21).
    A study was conducted in which MSMA was administered orally to 
pregnant female rats at doses of 0, 10, 100, or 500 mg/kg once daily on 
gestation days 6 through 15. No developmental effects were noted in the 
offspring of animals receiving 10 or 100 mg/kg MSMA. Decreased body 
weight gain and food consumption were noted in animals receiving 500 
mg/kg MSMA. The fetuses of this test group had lower mean fetal body 
weights when compared to control animals (Ref. 22).
    Based on the results of the animal studies discussed in the 
preceding paragraphs, EPA has determined that chronic exposure to 
either MSMA or DSMA can reasonably be anticipated to cause 
gastrointestinal toxicity, thyrotoxicity, nephrotoxicity, 
hepatotoxicity, and developmental and reproductive toxicity in humans.
    4. Carcinogenicity. Data regarding the carcinogenic potential of 
MSMA, DSMA, or MAA are extremely limited. In a study involving chronic 
administration of MAA, four groups of rats, each group containing 60 
males and 60 females, were fed diets containing 0 (the control group), 
50, 400, and 1,300 ppm of MAA for 104 weeks (Ref. 16). Because of 
excessive mortality, the 1,300 ppm concentration was reduced to 1,000 
ppm during week 53, and to 800 ppm at week 60. An increased incidence 
of parathyroid adenomas was observed in males receiving the 1,300 ppm 
(4/45) and 400 ppm (4/53) MAA diets, and in females (4/45) receiving 
the 1,300 ppm MAA diets. Evidence of parathyroid adenoma was also found 
in 1 of 52 male control rats. The increased incidence of parathyroid 
adenomas in the treated groups was found to be statistically 
significant relative to the control animals.
    As stated previously, cacodylic acid (dimethylarsonic acid, CAS No. 
75-60-5) is a known human metabolite of MSMA: Buchet and co-workers 
found that in human volunteers approximately 13 percent of an orally-
administered dose of MSMA is converted into cacodylic acid (Ref 9). EPA 
has recently categorized cacodylic acid as a Group B2 or probable human 
carcinogen (Ref. 23). EPA's classification of cacodylic acid as a Group 
B2 carcinogen was based on the results of two studies. The first was a 
2-year dietary feeding study in male and female rats receiving 
cacodylic acid at doses of 0, 2, 10, 40, and 100 ppm. An increase in 
urinary transitional cell bladder tumors with hyperplasia was noted in 
both sexes. The second study was a two year feeding study in which mice 
were fed diets containing 0, 8, 40, 200, and 500 ppm cacodylic acid. An 
increase in fibrosarcomas was noted in female mice fed 500 ppm 
cacodylic acid (23).
    EPA is unaware of any human epidemiological studies pertaining to 
MSMA, DSMA or MAA and cancer. However, because MAA has been associated 
with a possible increased incidence of parathyroid adenomas in 
experimental animals, and cacodylic acid (a known human metabolite of 
MSMA) is categorized by EPA as a probable human (B2) carcinogen, EPA 
believes that it is reasonable to assume that MSMA, DSMA, and MAA may 
be potential human carcinogens.
    5. Ecotoxicity. EPA has calculated a bobwhite quail oral LD50 
of 425.2 mg MSMA/kg (Ref. 24). This value was based on 51 percent 
active ingredient (MSMA) in the test material. EPA concluded from this 
study that MSMA is moderately toxic to bobwhite quail. Based on the 
same study, the petitioner gave an LD50 value of MSMA in bobwhite 
quail as 834 mg/kg. This value, however, was not adjusted to take into 
account that the test product contains only 51 percent MSMA. Moffett, 
et al., have investigated the [[Page 19706]] toxicity of MSMA and DSMA 
in honeybees (Refs. 25 and 26). In one of the studies, MSMA was sprayed 
onto honeybees at a rate of 4 lb/acre in a carrier volume of 20 
gallons/acre (Ref. 25). Mortalities were monitored for 14 days. Bee 
mortalities reached 50 percent after only approximately 2 days. 
Consequently, the investigators concluded that MSMA is highly toxic to 
honeybees (Ref. 25). In the other study MSMA and DSMA were fed to newly 
emerged honeybees in a 60 percent sucrose syrup (Ref. 26). Half-lives 
(i.e. the number of days for 50 percent mortality to occur) for MSMA 
and DSMA were 5.4 and 4.4 days at 100 parts per million by weight 
(ppmw) concentrations, and 2.5 and 1.2 days at 1,000 ppmw, 
respectively. The investigators concluded that both chemicals are 
``extremely toxic'' at 100 and 1,000 ppmw. Of the 14 herbicides tested 
in this study, MSMA and DSMA were found to be the most toxic to 
honeybees (Ref. 26). EPA does not yet have toxicity criteria for 
honeybees in EPA's Draft Hazard Assessment Guidelines for Listing 
Chemicals on the Toxic Release Inventory (Ref. 27). EPA believes, 
however, that the results of the studies described above strongly 
indicate that MSMA and DSMA are quite toxic to honeybees.
    The petitioner stated that for MSMA the acute median effective 
concentration (EC50) producing lethality in the freshwater alga 
Selenastrum capricornutum is 7.6 mg/L. The petitioner concluded (page 
68 of the petition) from this and other information that MSMA and DSMA 
are ``* * *.not particularly toxic to aquatic life * * *.'' However, 
based on the draft criteria developed by EPA to assess the hazard of 
chemical substances, EPA considers MSMA to be moderately toxic to 
aquatic life because the algal acute EC50 value for MSMA is 
between 100 micrograms per liter (ug/L) and 10 mg/L, the EC50 
range considered by EPA to be moderately toxic for aquatic biota (Ref. 
27). Other aquatic toxicity test data mentioned in the petition also 
indicate MSMA and DSMA are moderately acutely toxic (i.e., have 
EC50 or LC50 [median lethal concentration] values between 100 
ug/L and 10 mg/L) to aquatic biota. The 96-h LC50 of MSMA in 
bluegill, for example, is 4.2 mg/L.
    EPA obtained MSMA and DSMA aquatic toxicity data not mentioned by 
the petitioner (Ref. 28). The 28-day daphnid LC0 (zero percent 
lethal concentration) value for DSMA is 0.83 mg/L. The LC0 for 
DSMA in two species of invertebrates (a snail and a stonefly) and 
rainbow trout was found to be 0.97 mg/L (Ref. 28). A 28-day LC40 
(40 percent lethal concentration) value of 0.97 mg/L DSMA was reported 
for a gammarid amphipod invertebrate. In bluegills, the 96-h LC50 
for MSMA was found to be 1.9 mg/L. These data indicate that the 
toxicity of MSMA and DSMA to aquatic species is greater than that 
implied by the petitioner.

C. Environmental Fate

    Anthropogenic input of arsenic into the environment occurs through 
smelting, coal burning, and the use of arsenical herbicides (e.g., MSMA 
and DSMA) (Refs. 29 and 30). Numerous investigators have studied the 
environmental fate of arsenic-containing substances, including MSMA and 
DSMA. Results from these studies have been summarized (Refs. 29, 30, 
and 31). Arsenic-containing substances such as MSMA, DSMA, and MAA 
undergo chemical and biochemical transformations in the environment 
that include oxidation, reduction, and methylation. These 
transformations are largely controlled by soil, sediment absorption/
desorption processes, and affect the overall environmental distribution 
of arsenic-containing substances (Refs. 29, 30, and 31). Following 
their release into the environment, MAA, MSMA, and DSMA bind reversibly 
to ferrous and aluminum oxides contained on the surfaces of clay 
particles of soils and sediments. The bound form of these substances 
are insoluble in water, and exist in equilibrium with their unbound, 
soluble forms in the water present in soils and sediments. While 
unbound, MAA, MSMA, and DSMA undergo a cascade of biotic 
transformations that include oxidation, reduction, methylation, and 
demethylation (Ref. 31). Specifically, MAA, MSMA, and DSMA undergo 
oxidative demethylation to arsenate (H2AsO4-), an inorganic 
form of arsenic, and reductive methylation to cacodylic acid. The 
arsenate can be methylated back to MAA, and the two species will exist 
in equilibrium. Cacodylic acid can undergo further methylation to 
dimethylarsine or trimethylarsine, which will exist in equilibrium with 
cacodylic acid. These alkylarsine products volatilize from the soils 
and waters in which they were formed and enter the atmosphere. While in 
the atmosphere the alkylarsines can be transported to other locations, 
and the transformation cascade is repeated: the alkylarsines are 
oxidized back to cacodylic acid, MAA, and arsenate (Refs. 29-31). Thus, 
anthropogenic releases of MSMA or DSMA may indirectly lead to increased 
arsenic concentrations in areas where direct anthropogenic releases of 
these substances do not occur (Refs. 29-31). Terrestrial plants may 
accumulate arsenic-containing substances by root uptake from soils or 
by absorption of airborne arsenic deposited on plant leaves (Ref. 30).
    The predominant form of arsenic in surface waters (e.g., drinking 
waters, sea waters, etc.) is usually arsenate (H2AsO4-), an 
inorganic form of arsenic. Arsenate in surface waters can result from 
(or enter into) the transformation cascade described in the preceding 
paragraph. Above average exposure of the general population to arsenic 
from drinking waters is possible in areas of high natural arsenic 
levels in ground waters, or elevated arsenic levels in drinking waters 
due to industrial discharges, application of arsenic-containing 
pesticides, or leaching from hazardous waste facilities (Ref. 30). 
Individuals living in the vicinity of large smelters and other 
industrial emitters of arsenic substances may be exposed to greater 
than average amounts of arsenate as a result of environmental 
transformation of organic (e.g., MSMA or DSMA) or inorganic arsenic 
substances to arsenate (Ref. 30).
    Arsenate is an inorganic form of arsenic. An association between 
skin cancer and consumption of drinking water containing inorganic 
arsenic has been observed and confirmed (Ref. 32). Epidemiologic 
studies in areas where drinking waters containing inorganic arsenic 
concentrations ranging from 0.35 to 1.14 mg/L indicate elevated risks 
for cancers of the urinary bladder, kidney, skin, liver, lung, and 
colon in both men and women (Ref. 32). Increased incidences of cancer 
in individuals occupationally exposed to inorganic forms of arsenic 
have also been confirmed (Ref. 32). Because of these findings and the 
findings from other studies regarding human exposure to inorganic forms 
of arsenic and increased incidences of cancer, the National Toxicology 
Program categorizes arsenic and certain arsenic compounds (e.g., 
arsenate) as known human carcinogens (Ref. 32). EPA also categorizes 
inorganic arsenicals, including arsenate, as known human (Group A) 
carcinogens. The categorization by EPA of cacodylic acid as a Group B2 
(probable human) carcinogen was discussed in unit III.B.4. above. Thus, 
releases of MSMA or DSMA into the environment will lead to the 
formation of arsenate and cacodylic acid, which have been categorized 
by the National Toxicology Program and EPA as 
carcinogens. [[Page 19707]] 

D. Technical Summary

    MSMA and DSMA are highly water soluble organic arsenicals that are 
used as herbicides for the postemergent control of grassy weeds. MSMA 
and DSMA are poorly absorbed from the skin and lung, and well absorbed 
from the gastrointestinal tract. In the gastrointestinal tract, both 
MSMA and DSMA are expected to exist largely as MAA. Based on human and 
animal studies, MAA, MSMA, and DSMA are expected to be completely 
absorbed and widely distributed in humans following oral 
administration. In humans, MSMA is excreted largely unchanged in the 
urine, and approximately 13 percent is metabolized to cacodylic acid. 
MSMA and DSMA are not believed to be metabolized to inorganic 
arsenicals in humans.
    The mammalian LD50 values of MSMA and DSMA following acute 
oral exposure are quite high, indicating that these substances have a 
low order of acute lethality. Some animal studies indicate, however, 
that chronic exposure to lower doses of MSMA or DSMA produce 
gastrointestinal toxicity, thyrotoxicity, nephrotoxicity, 
hepatotoxicity, developmental and reproductive toxicity. Data regarding 
the carcinogenic potential of MSMA, DSMA, or MAA are extremely limited. 
A suggestion of an increased incidence of parathyroid adenomas was 
observed in rats administered MAA in their diets. Cacodylic acid, a 
known human metabolite of MSMA, is categorized by EPA as a Group B2 
(probable human) carcinogen. Because MSMA and, presumably, DSMA are 
converted into cacodylic acid, MSMA and DSMA may also be carcinogenic 
in humans.
    MSMA and DSMA are moderately toxic to terrestrial and aquatic 
species that include, among others, bobwhite quail, honeybees, 
freshwater algae, fish, and daphnids.
    In the environment, MSMA, DSMA, and MAA undergo a cascade of 
chemical and biochemical transformations that are controlled by soil, 
sediment adsorption/desorption processes. In this cascade, MSMA, DSMA, 
and MAA are converted into arsenate (inorganic arsenic), cacodylic 
acid, dimethylarsine and trimethylarsine. Inorganic arsenicals, 
including arsenate, are categorized by the National Toxicology Program 
and EPA as known human carcinogens. In addition, cacodylic acid is 
categorized by EPA as a Group B2 or probable human carcinogen.

IV. Rationale for Denial

    EPA is denying the petition to delete MSMA and DSMA from the 
section 313 list of toxic chemicals. This denial is based on the 
Agency's determination that MSMA and DSMA: (1) May cause chronic toxic 
effects in humans; and (2) are potential carcinogens. In regard to the 
latter point, EPA has determined that because MSMA and, undoubtedly, 
DSMA are metabolized in humans to cacodylic acid (a probable human 
carcinogen), it is reasonable to assume that MSMA and DSMA are also 
probable human carcinogens. In addition, it has been demonstrated that 
MSMA and DSMA are converted into arsenate (an inorganic arsenic) and 
cacodylic acid in soils and sediments. Inorganic arsenics, including 
arsenate, are categorized by the National Toxicology Program and EPA as 
known human carcinogens. EPA concludes that MSMA and DSMA meet the 
EPCRA section 313(d)(2)(B) criteria because they can reasonably be 
anticipated to cause cancer in humans as a result of their metabolism 
to cacodylic acid or their environmental conversion to cacodylic acid 
and arsenate. Thus, in accordance with EPCRA section 313(d)(2), EPA has 
determined that MSMA and DSMA exhibit high chronic toxicity and, 
therefore, should not be deleted from the section 313 list of toxic 
chemicals.
    EPA's denial of the petition to delist MSMA and DSMA from the 
section 313 list of toxic chemicals is based, in part, on the 
conversion of these substances to substances that are regarded as being 
either known or probable human carcinogens, and is consistent with past 
Agency decisions regarding section 313 delisting petitions. [See, e.g., 
Chromium (III) Oxide (56 FR 58859, November 22, 1991)]

V. References

    (1) Shah, P.V., Fisher, H.L., Sumler, M.R., Monroe, R.J., Chernoff, 
N., Hall, L.L. (1987) Comparison of the Penetration of 14 Pesticides 
Through the Skin of Young and Adult Rats. J. Toxicol. Environ. Health. 
21:353-366.
    (2) Toxicological Profile For Arsenic (Update). Agency for Toxic 
Substances and Disease Registry (ATSDR) Report No. ATSDR/TP-92/02; pp. 
7-84.
    (3) Shariatpanahi, M., Anderson, A.C. (1984) Distribution and 
Toxicity of Monosodium Methanearsonate Following Oral Administration of 
the Herbicide to Dairy Sheep and Goats. J. Environ. Sci. Health B19(4 
5):427-439.
    (4) Jaghabir, M.D., Abdelghani, A.A., Anderson, A.C. (1991) 
Absorption, Distribution, and Elimination of Arsenic in New Zealand 
White Rabbits (Oryctalagus cuniculus) Following Multiple Oral Doses of 
Monosodium Methane Arsonate. Environmental Toxicology and Water 
Quality: An International Journal 6:113-119.
    (5) Stevens, J.T., DiPasquale, L.C., Farmer, J.D. (1979) The Acute 
Inhalation Toxicology of the Technical Grade Organoarsenical 
Herbicides, Cacodylic Acid and Disodium Methanearsonic Acid; A Route 
Comparison. Bull. Environm. Contam. Toxicol. 21:304-311.
    (6) Goyer, R.A. (1991) Toxic Effects of Metals. In: Amdur, M.O., 
Doull, J. Klaassen, C.D. eds., Casarett and Doull's Toxicology, The 
Basic Science of Poisons. Fourth Edition. Pergamon Press: New York; pp. 
631-632.
    (7) U.S. Environmental Protection Agency. (1984). Health Assessment 
Document for Arsenic. Criteria and Assessment Office, Research Triangle 
Park, NC, Report No. EPA 600/8-83-021F.
    (8) U.S. Environmental Protection Agency. (1991) Data Evaluation 
Report: Metabolism Data on [14C-methyl]MSMA. MRID No. 42010501 
(Office of Pesticide Programs).
    (9) Buchet, J.P., Lauwerys, R., Roels, H. (1981) Comparison of the 
Urinary Excretion of Arsenic Metabolites After a Single Oral Dose of 
Sodium Arsenite, Monomethylarsonate, or Dimethylarsinate in Man. Int. 
Arch. Occup. Environ. Health 48:71-79.
    (10) U.S. Environmental Protection Agency. (1991) Data Evaluation 
Report: Rat Acute Oral Toxicity of DSMA 81P in the Rat. MRID No. 
418920-04.
    (11) Gaines, T.B., Linder, R.E. (1986) Acute Toxicity of Pesticides 
in Adult and Weanling Rats. Fundam. Appl. Toxicol. 7:299-308.
    (12) U.S. Environmental Protection Agency. (1991) Data Evaluation 
Report: Rabbit Acute Dermal Toxicity of DSMA. MRID No. 418920-05.
    (13) U.S. Environmental Protection Agency. (1991) Data Evaluation 
Report: Rabbit Acute Dermal Toxicity of MSMA. MRID No. 418900-01.
    (14) U.S. Environmental Protection Agency. (1991) Data Evaluation 
Report: Acute Inhalation Toxicity of DSMA 81P in the Rat. MRID No. 
418920-06.
    (15) Toxicological Profile For Arsenic. Agency for Toxic Substances 
and Disease Registry (ATSDR) Report No. ATSDR/TP-92/02; pp. 7-84.
    (16) U.S. Environmental Protection Agency. (1991) Data Evaluation 
Report: Methanearsonic Acid Combined Chronic Feeding and Oncogenicity 
Study in the Rat. MRID No. 41669001.
    (17) Jaghabir, M.T.W., Abdelghani, A.A., Anderson, A.C. (1989) 
[[Page 19708]] Histopathological Effects of Monosodium Methanearsonate 
(MSMA) on New Zealand White Rabbits (Oryctalagus cuniculus). Bull. 
Environ. Contam. Toxicol. 42:289-293.
    (18) Prukop, J.A., Savage, N.L. (1986) Some Effects of Multiple, 
Sublethal Doses of Monosodium Methanearsonate (MSMA) Herbicide on 
Hematology, Growth, and Reproduction of Laboratory Mice. Bull. Environ. 
Contam. Toxicol. 36:337-341.
    (19) U.S. Environmental Protection Agency. (1989) Data Evaluation 
Report: Methanearsonic Acid Fifty Two Week Chronic Oral Toxicity Study 
in Beagle Dogs. MRID No. 405461-01/412664-01.
    (20) U.S. Environmental Protection Agency. (1986) Data Evaluation 
Report: Methanearsonic Acid Teratology Study in the Rabbit. MRID No. 
159390-01.
    (21) U.S. Environmental Protection Agency. (1994) Data Evaluation 
Report: a Two Generation Reproduction Study in Rats with Methanearsonic 
Acid (MAA). MRID No. 431783-01.
    (22) U.S. Environmental Protection Agency. (1990) Data Evaluation 
Report: a Teratology Study in Rats with Methanearsonic Acid. MRID No. 
419264-01.
    (23) U.S. Environmental Protection Agency. (1994) Carcinogenicity 
Peer Review Document for Cacodylic Acid.
    (24) U.S. Environmental Protection Agency. (1991) Data Evaluation 
Report: Monosodium Methane Arsonate (MSMA); Avian Single Dose Oral 
LD50 Test (Bobwhite Quail). MRID No. 416100-02.
    (25) Moffett, J.O., Morton, H.L., MacDonald, R.H. (1972) Toxicity 
of Some Herbicidal Sprays to Honey Bees. J. Econ. Entomol. 65:32-36.
    (26) Morton, H.L., Moffett, J.O., MacDonald, R.H. (1972) Toxicity 
of Herbicides to Newly Emerged Honey Bees. Environ. Entomol. 1:102-104.
    (27) Hazard Assessment Guidelines for Listing Chemicals on the 
Toxic Release Inventory. Revised Draft (May 26, 1992). Office of 
Pollution Prevention and Toxics, U.S. Environmental Protection Agency.
    (28) Eisler, R. (1988) Arsenic Hazards to Fish, Wildlife, and 
Invertebrates: A Synoptic Review. Dept. of the Interior, U.S. Fish 
Wildl. Serv. Biol. Rep. 85(1.12) .
    (29) Menzer, R.E. (1991) Water and Soil Pollutants. In: Amdur, 
M.O., Doull, J. Klaassen, C.D. eds., Casarett and Doull's Toxicology, 
The Basic Science of Poisons. Fourth Edition. Pergamon Press: New York; 
pp. 891-893.
    (30) Toxicological Profile For Arsenic. Agency for Toxic Substances 
and Disease Registry (ATSDR) Report No. ATSDR/TP-92/02; pp. 99-108.
    (31) Woolson, E.A. (1977) Fate of Arsenicals in Different 
Environmental Substrates. Environmental Health Perspectives 19:73-81.
    (32) Seventh Annual Report on Carcinogens: 1994 Summary. United 
States Department of Health and Human Services, National Toxicology 
Program; pp. 21-26.

VI. Administrative Record

    The record supporting this decision is contained in docket control 
number OPPTS-400092. All documents, including an index of the docket, 
are available to the public in the TSCA NonConfidential Information 
Center (NCIC), also known as the Public Docket Office, from noon to 4 
p.m., Monday through Friday, excluding legal holidays. The TSCA NCIC is 
located at EPA Headquarters, Rm. NE-B607, 401 M St., SW., Washington, 
DC 20460.

List of Subjects in 40 CFR Part 372

    Environmental protection, Chemicals, Community right-to-know, 
Reporting and recordkeeping requirements, and Toxic chemicals.

    Dated: April 14, 1995.
Lynn R. Goldman,
Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

[FR Doc. 95-9782 Filed 4-17-95; 12:11 pm]
BILLING CODE 6560-50-F