August, 1987
820K88102
DRAFT
AMMONIUM SULFAMATE
Health Advisory
Office of Drinking Water
U»S. Environmental Protection Agency
I. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Drinking
Water (ODW), provides information on the health effects, analytical method-
ology and treatment technology that would be useful in dealing with the
contamination of drinking water. Health Advisories describe nonregulatory
concentrations of drinking water contaminants at which adverse health effects
would not be anticipated to occur over specific exposure durations. Health
Advisories contain a margin of safety to protect sensitive members of the
population.
Health Advisories serve as informal technical guidance to assist Federal,
State and local officials responsible for protecting public health when
emergency spills or contamination situations occur. They are not to be
construed as legally enforceable Federal standards. The HAs are subject to
change as new information becomes available.
\
Health Advisories are developed for one-day, ten-day, longer-term
(approximately 7 years, or 10% of an individual's lifetime) and lifetime
exposures based on data describing noncarcinogenic end points of toxicity.
Health Advisories do not quantitatively incorporate any potential carcinogenic
risk from such exposure. For those substances that are known or probable
human carcinogens, according to the Agency classification scheme (Group A or
B)f Lifetime HAs are not recommended. The chemical concentration values for
Group A or B carcinogens are correlated with carcinogenic risk estimates by
employing a cancer potency (unit risk) value together with assumptions for
lifetime exposure and the consumption of drinking water. The cancer unit
risk is usually derived from the linear multistage model with 95% upper
confidence limits. This provides a low-dose estimate of cancer risk to
humans that is considered unlikely to pose a carcinogenic risk in excess
of the stated values. Excess cancer risk estimates may also be calculated
using the One-hit, Weibull, Logit or Probit models. There is no current
understanding of the biological mechanisms involved in cancer to suggest that
any one of these models is abl« to predict risk more accurately than another.
Because each model is based on differing assumptions, the estimates that are
derived can differ by several orders of magnitude.
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II. GENERAL INFORMATION AMD PROPERTIES
CAS Mo. 7773-06-0
Structural Formula
O
I
H2N - S - O - NH4
O
ammonium sulfamate
Synonyms
0 Amicide; Amidosulfate; Ammonium amidosulfate; Ammonium amidosulfonate;
Ammonium amidotrioxosulfate; AMS; Fyran 206k; Ikurin.
Uses
• Herbicide used to control woody plant species.
Nay be used for poison ivy control in apple and pear orchards
x (Meister, 1983).
Properties (Meister, 1983)
Molecular Weight 114.14
Physical State (25°C) Colorless crystals
Boiling Point ~
Melting Point 131 to 1328C
Density (20°C) >1
Vapor Pressure Not available
Water Solubility Highly soluble
Log Octanol Water/Partition —
Coefficient
Taste Threshold --
Odor Threshold —
Conversion Factor —
Occurrence
* No information was found in the available literature on the occurrence
of ammonium sulfamate.
Environmental Fate
0 Konnai et al. (1974) showed that ammonium sulfamate was very mobile
in soil.
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III. PHARMACOKINETICS
Absorption
0 No information was found in the available literature on the absorption
of ammonium sulfamate.
Distribution
0 No information was found in the available literature on the distribution
of ammonium sulfamate.
Metabolism
0 The metabolism of ammonium sulfamate in the urine of dogs was reported
by Bergen and Wiley (1938); however, details of the study were not
clearly defined for assessment.
Excretion
Bergen and Wiley (1938) reported 80 to 84% excretion of sulfamic acid
in the urine of two dogs following oral administration of ammonium
sulfamate in capsules for 5 days.
IV. HEALTH EFFECTS
Humans
No information was found in the available literature on the health
effects of ammonium sulfamate in humans.
Animals
Short-term Exposure
e No information was found in the available literature on the effects
of short-term exposure to ammonium sulfamate in animals.
Dermal/Ocular Effects
0 Five rats received a 20% aqueous solution of ammonium sulfamate (dose
level not specified) on the shaved skin of the back. They were
killed after 16 treatments on the 27th day of the period (Read and
Hueber, 1938). Another five rats received a 50% aqueous solution of
ammonium sulfamate on the shaved skin of the back. These animals
were killed after 11 treatments on the 19th day of the study. It
should be noted that the animals were not prevented from licking the
chemical. Investigators reported that there were no gross pathological
changes of importance in any of the animals. On microscopic patho-
logical examination of the animals, the spleen of 9 of 10 animals had
numerous macrophages with brown pigment. The stomach sections of seven
animals, revealed a brown, granular material in the surface capillaries
of the mucosa.
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Ammonium Sulfanate August, 1987
• Read and Hueber (1938) orally administered 1 mL of a 50% aqueous
solution of ammonium sulfamate (1.7 gfkg/day) to 10 rats on alternate
days. Five rats were killed on the 27th day of the study after nine
treatments, and the remaining five were killed on the 42nd day of the
study after 15 treatments. Investigators reported that there were no
gross pathological changes of importance in any of the animals.
Microscopic pathology indicated the following: in one animal, super-
ficial capillaries of the stomach mucosa occasionally contained
yellow-brown granulesi in three animals, there was slight vacuolation
of the cytoplasm of liver cells about the central veins, but these
changes were very mild; and in the spleen, three of the sections had
moderate numbers of macrophages filled with hemosiderin. A fourth
spleen section showed marked erythrophagia.
Long-term Exposure
0 Gupta et al. (1979) reported the results of a 90-day study involving
oral administration of 0, 100, 250 or 500 mg/kg of ammonium sulfamate
to rats 6 days a week. No adverse effects were observed with respect
to appearance, behavior or survival of animals. No significant
difference in the body weights of rats was observed except in the
case of rats receiving 500 mg/kg, where body weight was signifi-
cantly less than controls after the end of 60 days. No significant
changes in relative organ weights were noticed in any group of rats.
Hematological examination conducted at 30, 60 and 90 days revealed
nonsignificant increases in the numbers of neutrophils in the female
adult and male weanling rats (500 mg/kg dose level) after 90 days.
In the histological examination, organs in all the groups of animals
appeared normal except that the liver of one adult rat (500 mg/kg)
showed slight fatty degenerative changes after 90 days.
0 Rosen et al. (1965) reported the findings of a study in female rats
following administration of ammonium sulfamate at dietary levels of 1.1%
(10 g/kg/day) or 2.1% (20 g/kg/day) for 105 days. No effect was detected
at the 1% (10 g/kg/day) level of feeding, but growth retardation
and a slight cathartic effect were observed at the 2% (20 g/kg/day)
dietary level. No otheŁ information was provided by the authors.
0 Sherman and Stula (1966) reported the results of a 19-month feeding
study in 29-day-old CHR-CD male and female rats. Ammonium sulfamate
was fed at dietary concentrations of 0, 350 (350 mg/kg) or 500
(500 mg/kg) ppm without any clinical or nutritional evidence of toxieity*
there were no histopsthological changes that could be attributed to
the feeding of the test chemical. The observed pathologic lesions
were interpreted as a result of spontaneous diseases.
Reproductive Effects
• Sherman and Stula (1966) reported the results of a three-generation
reproduction study in rats. Rats receiving 0, 350 (350 mg/kg) or
500 (500 mg/kg) ppm ammonium sulfamate in the diet showed no evidence
of toxicity as measured by histopathological evaluation and reproduction
and lactation indices.
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Developmental Effects
0 No information was found in the available literature on the develop-
mental effects of ammonium sulfamate.
Mutagenicity
0 No information was found in the available literature on the mutagenic
effects of ammonium sulfamate.
Cajrcinogenicity
0 No information was found in the available literature on the carcinogenic-
effects of ammonium sulfamate.
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories (HAs) are generally determined for one-day, ten-day,
longer-term (approximately 7 years) and lifetime exposures if adequate data
are available that identify a sensitive noncarcinogenic end point of toxicity.
Hie HAs for noncarcinogenic toxicants are derived using the following formula:
HA = (NOAEL or LOAEL) x (BW) = _ mg/L ( _ ug/L)
(UF) x ( _ L/day)
where:
NOAEL or LOAEL » No- or Lowest-Observed-Adverse-Effect-Level
in mg/kg bw/day.
BW » assumed body weight of a child (10 kg) or
an adult (70 kg).
UF = uncertainty factor (10, 1 00 or 1,000), in
accordance with NAS/ODW guidelines.
_ L/day = assumed daily water consumption of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
No data were located in the available literature that were suitable for
deriving a One-day HA value for ammonium sulfamate. It is recommended that
the Longer-term HA value for the 10-kg child (21.4 mg/L, calculated below)
be used at this time as a conservative estimate of the One-day HA value.
Ten-day Health Advisory
No data on ammonium sulfamate toxicity were located in the available
literature that were suitable for calculation of a Ten-day HA value. It is
recommended that the Longer-term HA value for the 10-kg child (21.4 mg/L,
calculated below) be used at this time as a conservative estimate of the
Ten-day HA value.
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Longer-term Health Advisory
The subchronic oral toxicity study in rats by Gupta et al. (1979) may be
considered for the Longer-term HA. In this study, rats (female adults and
male and female weanlings) received ammonium sulfamate orally at dose levels
of 0, 100, 250 or 500 mg/kg/day for 90 days. Hematological and histological
examinations at 30, 60 and 90 days revealed nonsignificant changes in hemato-
logical and histological measures. However, adult rats fed 500 mg/kg ammonium
sulfamate showed lesser weight gain compared to other groups.
Using 250 mg/kg/day as a No-Observed-Adverse-Effect-Level (NOAEL), a
Longer-term HA for the 10-kg child is calculated as follows:
Longer-term HA = (250 mg/kg/day) (10 kg) (6/7) , 21.4 mg/L (21,400 ug/L)
(100) (1 L/day)
where:
250 mg/kg/day « NOAEL, based on the absence of hematological and
histopathological changes in rats.
10 kg * assumed body weight of a child.
6/7 » conversion from 6 days to 7 days.
100 * uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
1 L/day * assumed daily water consumption of a child.
For the 70-kg adult:
Longer-term HA = (250 mg/kg/day) (70 kg) (6/7) . 75 /L (75/0oo ug/L)
(100) (2 L/day)
where:
250 mg/kg/day = NOAEL, based on the absence of hematological and
histopathological changes in rats.
70 kg = assumed body weight of an adult.
6/7 = conversion from 6 days to 7 days.
100 = uncertainty factor, chosen in accordance with NAS/OEW
guidelines for use with a NOAEL from an animal study.
2 L/day = assumed daily water consumption of an adult.
Lifetime Health Advisory
The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective of noncar-
cinogenic adverse health effects over.a lifetime exposure. The Lifetime HA
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is derived in a three-step process. Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI). The RfD is an esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(s). From the RfD, a Drinking Water Equivalent Level
(DWEL) can be determined (Step 2). A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult. The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC). The RSC from drinking
water is based on actual exposure data or, if data are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals. If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.
exposure to this chemical.
The study by Gupta et al. (1979) has been selected to serve as the basis
for determination of the Lifetime HA even though the results of this subchronic
study were based on 90 days' exposure. In this study, rats (female adults
and weanling males and females) received ammonium sulfamate orally in drinking
water at dose levels of 0, 100, 250 or 500 mg/kg/day for 90 days. The NOAEL
was identified as 250 mg/kg/day, since the highest dose level of 500 mg/kg/day
was associated with decreased body weight gain in rats over a 90-day exposure
period). In a chronic feeding study reported by Sherman and Stula (1966)
in rats, ammonium sulfamate was fed to rats at dietary levels of 0, 350 or
500 ppm over a 19-month period. The authors stated that these dose levels
did not produce any significant clinical or histological changes in rats
receiving the test compound, and any changes recorded were interpreted as
being lesions of spontaneous diseases.
Using a NOAEL of 250 mg/kg/day, the Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (250 mg/kg/day) (6/7) = 0<214 mg/kg/day
(1,000)
where:
250 mg/kg/day = NOAEL.
6/7 = conversion from 6 days to 7 days.
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study
of less than a lifetime exposure.
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Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL - <0«214 mg/kg/day) (70 kg) . 7>5 mg/L (7f5oo ug/L)
(2 L/day)
where:
0.250 mgAg/day * RfD.
70 kg - assumed body weight of an adult.
2 L/day * assumed daily water consumption of an adult.
Step 3: Determination of the Lifetime Health Advisory
Lifetime HA - (7.5 mg/L) (20%) - 1.5 mg/L (1,500 ug/L)
where:
7.5 mg/L « DWEL.
20% * assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
0 No studies were found in the available literature investigating
the carcinogenic potential of ammonium sulfamate. Applying the
criteria described in EPA's final guidelines for assessment of
carcinogenic risk (U.S. EPA, 1986), ammonium sulfamate may be
classified in Group D: not classified. This category is used for
substances with inadequate animal evidence of carcinogenicity.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 The American Conference of Government Industrial Hygienists (ACGIH)
has adopted a Threshold Limit Value-Time-Weighted Average (TLV-TWA)
of 10 mg/m3 and a TLV short-term exposure limit (STEL) of 20 mg/m3
for inhalation exposure (ACGIH, 1984).
VII. ANALYTICAL METHODS
0 There is no standardized method for determination of ammonium sulfamate
in water samples. A procedure has been reported for the estimation of
ammonium sulfamate in certain foods, however (U.S. FDA, 1969). This
procedure involves a colorimetric determination of ammonium sulfamate
based on the liberation of 504 and reduction it to f^S, which is
measured after treating with zinc, p-aminodimethylaniline and ferric
chloride to form methylene blue.
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VIII. TREATMENT TECHNOLOGIES
0 No information was found in the available literature on treatment
technologies capable of effectively removing ammonium sulfamate from
contaminated water.
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IX. REFERENCES
ACGIH. 1984. American Conference of Governmental Industrial Hygienists.
Documentation of the threshold limit values for substances in workroom
air, 3rd ed. Cincinnati, OH: ACGIH.
Bergen, D.S. and P.M. Wiley.* 1938. The metabolism of sulfamic acid and
ammonium sulfamate. Unpublished report. Submitted to U.S. EPA, Office
of Pesticide Programs, Washington, DC.
Gupta, B.N., R.N. Khanna and K.K. Datta. 1979. Toxicological studies of
ammonium sulfamate in rats after repeated oral administration. Toxicologyc
13:45-49.
Konnai, M., Y. Takeuchi and T. Takematsu. 1974. Basic studies on the residues
and movements of forestry herbicides in soil. Bull. Coll. Agric.
Utsunomiya Univ. 9(1):995-1012.
Meister, R., ed. 1983. Farm chemicals handbook. Willoughby, OH: Meister
Publishing Co.
Read, W.T. and K.C. Hueber.* 1938. The pathology produced in rats following
the administration of sulfamic acid and ammonium sulfamate. Unpublished
report. MRID GS0016-0040.
Rosen, D.E., C.J. Krisher, H. Sherman and E.E. Stula. 1965. Toxicity studies
on ammonium sulfamate. The Toxicologist. Fourth Annual Meeting, Williams-
burg, VA. March 8-10.
Sherman, H. and E. Stula.* 1966. Toxicity studies on ammonium sulfamate.
Unpublished report. MRID GS0016-0038.
U.S. EPA. 1986. U.S. Environmental Protection Agency. Guidelines for
carcinogen risk assessment. Fed. Reg. 51 (185):33992-34003. September 24.
U.S. FDA. 1969. U.S. Food and Drug Administration. Pesticide analytical
manual, Vol. II. Washington, DC.
•Confidential Business Information submitted to the Office of Pesticide
Programs.
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