820K88011 August' 1987
FENAMIPHOS
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), 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 ^ble 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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Fenamiphos
August, 1987
II. GENERAL INFORMATION AND PROPERTIES
CAS No. 22224-92-6
Structural Formula
-2-
CH3S
VX ° H
>\ II I
XV0-P-N-CH(CH,)2
OC2H$
(1-Methylethyl)-ethyl-3-methyl-4-(methylthio)phenyl-phosphoramidate
Synonyms
0 Nemacur; B 68138; Bay 68138; Bayer 68138; ENT 27572; Phenamiphos
(Meister, 1983).
Uses
0 Systemic nematicide (Meister, 1983).
Properties {Meister, 1983)
Chemical Formula
Molecular Weight
Physical State (at 25°C)
Boiling Point
Melting Point
Density
Vapor Pressure (30°C)
Water Solubility (25°C)
Log Octanol/Water Partition
Coefficient
Taste Threshold
Odor Threshold
Cor version Factor
C13H22°3NSP
303 (calculated)
Brown, waxy solid
49.2°C
7.5 x 1C~7 ran Hg
400 ng/L
Occurrence
Fenamiphos has been found in only 2 ground water samples out of
452 analyzed (STORET, 1987). Both locations were in California with
the highest concentration found being 5 ug/L. No surface water
locations were tested.
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Fenamiphos August, 1987
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Environmental Fate
0 Ring-labeled 14c-fenamiphos {radiochemical purity 94%), at 1 and 10 ppm,
degraded with half-lives of 7 to 1 4 days in a buffered aqueous solution
at pH 3 and >30 days at pH 9, and appeared to be stable at pH 7 when
incubated in the dark at 30°C (McNamara and Wilson, 1981). In the
pH 3 buffer solution, the primary degradation product was deaininated
fenamiphos accounting for 74 to 78% of the applied material. Degradates
identified in methylene chloride extracts from the pH 3, 7 and 9
solutions included fenamiphos sulfoxide, fenamiphos sulfone, fenamiphos
phenol, fenamiphos sulfoxide phenol and fenamiphos sulfone phenol.
0 Ring-labeled 1^C-fenamiphos (radiochemical purity >99%), at 12 ppm,
degraded with a half-life of 2 to 4 hours in pH 7 buffered water
irradiated with artificial light (approximately 5200 uW/cm2, 300 to
600 nm) (Dime et al., 1983). After 24 hours of irradiation, fenamiphos
accounted for approximately 4% of the applied radioactivity, fenamiphos
sulfonic acid phenol for approximately 19%, fenamiphos sulfoxide for
approximately 17%, fenamiphos sulfonic acid for approximately 6% (tenta-
tive identification), and fenamiphos sulfoxide phenol for approximately
1%. In the dark control, fenamiphos accounted for approximately 94% of
the applied at 24 hours post-treatment.
0 Ring-labeled 14c-fenamiphos (radiochemical purity >99%), at approxi-
mately 20 ppm, degraded with a half-life of <1 hour on sandy loam soil
irradiated with artificial light (approximately 6200 uW/cm2, 300 to
600 nm) (Dime et al., 1983). After 48 hours of irradiation, fenamiphos
and the degradates fenamiphos sulfoxide and fenamiphos sulfone accounted
for approximately 12, 55 and 6% of the extractable radioactivity,
respectively. In the dark control, fenamiphos accounted for approxi-
mately 93% of the extractable compound at 48 hours post-treatment.
0 14c-Fenamiphos (purity 86%), at 3 ppm, degraded with a half-life of
<4 days in silty clay loam soil previously treated with fenamiphos
(Green et al., 1982). Fenamiphos sulfoxide comprised up to approxi-
mately 74% of the applied radioactivity (maximum at 11 days post-
treatment); fenamiphos sulfone comprised approximately 10% and volatile
14c-residues comprised 17% of the applied material at 55 days post-
treatment. At 55 days post-treatment, 1.13% of the applied fenamiphos
remained undegraded in the soil previously treated with fenamiphos,
5.41% remained undegraded in soil with no prior history of fenamiphos
treatment, and 40.58% remained undegraded in sterile soil. Fenamiphos
sulfoxide was the major degradate in all three treatments.
o 14c-Fenamiphos (test substance uncharacterized), at 0.29 to 2.30 ug/ml
of water, was adsorbed to sandy loam and clay loam soils with 26.3 to
30.0% and 42.2 to 52.3% of the applied radioactivity, respectively,
adsorbed after 16 hours (Church, 1970).
0 Fenamiphos (3 lb/gallon SC and 15% G), at approximately 20 Ib ai/A,
was mobile in columns (16-cm length) of sandy soil eluted with 10
inches of water. Fenamiphos was detected throughout the columns, and
0.9 to 2.2% of the applied material was recovered in the leachate
(Gronberg and Atwell, 1980).
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Fenamiphos August, 1987
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0 Aged (30 days) 14C-fenamiphos residues, at approximately 4 Ib ai/A,
were slightly mobile in a column (12-inch length) of sandy loam soil
leached with 22.5 inches of water; approximately 2.3% of the applied
radioactivity leached from the column and approximately 91% of the
applied radioactivcity remained in the top 5 inches of the soil
column (Tweedy and Houseworth, 1980).
III. PHARMACOKINETICS
Absorption
0 Gronberg (1969) administered 14C-labeled fenamiphos (99% purity)
by oral intubation to rats. Only 5 to 7% was recovered in feces,
indicating that 93 to 95% was absorbed from the gastrointestinal
tract.
Distribution
0 Gronberg (1969) administered single oral doses of 2 mg/kg of ethyl-
14C-fenamiphos (99% purity) by oral intubation to rats. Forty-eight
hours after treatment, residues measured in tissues were: brain
<0.1 ppm; heart 0.1 ppm; liver 0.8 to 1.7 ppm; kidney 0.4 to 0.5 ppm;
fat 0.2 to 0.4 ppm; muscle <0.1 ppm; and gastrointestinal tract 0.2 ppm.
Metabolism
0 In studies conducted by Gronberg (1969), rats were administered 2 mg/kg
oral doses of fenamiphos (99% purity) using ethyl-14c, methylthio-3H or
isopropyl-14C label. The authors proposed a pathway of fenamiphos
metabolism involving oxidation to the sulfoxide and sulfone analogs.
Subsequent hydrolysis, conjugation and excretion via urine gave high
molecular-weight compounds (600 to 800). No other details were
provided.
Excretion
Gronberg (1969) administered ethyl-14c, methylthio-3H or isopropyl-
14c-labeled fenamiphos (2 mg/kg, 99% purity) to rats by gavage.
Thirty-nine to forty-two percent or 50% of the administered radio-
activity was expired as CO2, respectively. Thirty-eight to 40% of
the ethyl-14c labels were in urine and 5% in feces, respectively.
Eighty percent of the methylthio-^H label was found in urine. The
majority of the administered dose was excreted 12 to 15 hours after
treatment.
IV. HEALTH EFFECTS
Humans
0 No information on the health effects of fenamiphos in humans was
found in the available literature.
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Animals
Short-term Exposure
0 NIOSH (1985) reported the acute oral LD$Q of fenamiphos in the rat,
mouse, dog, cat, rabbit and guinea pig as 8, 22.7, 10, 10, 10 and
75 mg/kg, respectively.
0 Kimmerle and Lorke (1970) fed chickens (eight/dose) diets containing
technical fenamiphos at levels of 0, 1, 3, 10 or 30 ppm active
ingredient (a.i.) for 30 days. The authors stated that this corre-
sponded to doses of 0, 2, 5, 16 or 26 mg/kg/day. Following treatment,
feed consumption, neurotoxicity and cholinesterase (ChE) activity
were determined. Histopathological sections of the brain, spinal
cord and peripheral nerves were also evaluated. No neuropathy was
observed at any dose level tested. No ChE symptoms were reported,
but ChE activity in whole blood was inhibited in a dose-dependent
manner from 21% at 3 ppm to 65% at 30 ppm. Based on ChE inhibition,
a No-Observed-Adverse-Effect-Level (NOAEL) of 1 ppm (2 mg/kg/day) was
identified.
Dermal/Ocular Effects
0 DuBois et al. (1967) reported acute dermal LD5Q values of 78 mg/kg
for rats and 55 mg/kg for guinea pigs.
0 Crawford and Anderson (1973) applied 120 mg of a spray concentrate of
fenamiphos (37.47% a.i.) to shaved intact and abraded skin of six New
Zealand White rabbits and reported slight erythema 24 and 72 hours
post-treatment.
0 In ocular studies conducted by Crawford and Anderson (1973), the
instillation of 0.1 mL of a spray concentrate of fenamiphos (37.47%
a.i.) into the eyes of New Zealand White rabbits resulted in corneal
and conjunctival damage at 24 and 72 hours post-treatment. These
effects had not subsided by 21 days post-treatment.
Long-term Exposure
0 In feeding studies conducted by Mobay Chemical Corporation (1983),
Fischer 344 rats (50/sex/dose) were administered technical fenamiphos
(89% purity) at dose levels of 0, 0.36, 0.60 or 1.0 ppm a.i. for
90 days. Assuming that 1 ppm in the diet of rats is equivalent to
0.05 mg/kg/day (Lehman, 1959), this corresponds to dose levels of 0,
0.018, 0.03 or 0.05 mg/kg/day. Following treatment, brain, plasma
and erythrocyte ChE levels were measured. Cholinesterase levels were
not significantly reduced at any dose tested. Other parameters were
not evaluated. The author reported a NOAEL of 1 ppm (0.05 mg/kg/day,
the highest dose tested).
0 Loser and Kimmerle (1968) fed Wistar rats (15/sex/dose) fenamiphos
for 90 days in the diet at dose levels of 0, 4, 8, 16 or 32 ppm
active ingredient. Assuming that 1 ppm in the diet is equivalent to
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Fenamiphos August, 1987
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0.05 mg/kg/day (Lehman, 1959), this corresponds to doses of 0, 0.2,
0.4, 0.8 or 1.6 mg/kg/day. Following treatment, body weight, food
consumption, hematology, ChE activity, urinalysis and gross pathology
were evaluated. No histologic examination was performed. No effects
on any end point were reported except for ChE inhibition. No effect
was seen at 4 ppm (0.2 mg/kg/day). At 8 ppm (0.4 mg/kg/day), ChE in
whole blood and plasma was decreased by 11% and 19%, respectively.
Higher doses produced larger decreases in ChE. Based on these data,
a NOAEL of 4 ppm (0.2 mg/kg/day) was identified.
0 Loser (1970) administered technical fenamiphos (99.4% purity) in the
feed of beagle dogs (two/sex/dose) for 3 months at dietary levels of
0, 1, 2 or 5 ppm. Assuming that 1 ppm in the diet of dogs is equivalent
to 0.025 mg/kg/day (Lehman, 1959), this corresponds to doses of 0,
0.025, 0.05 or 0.125 mg/kg/day. Untreated controls (three/sex) were
run concurrently. Following treatment, body weight, feed consumption,
clinical chemistry, urinalysis, ChE activity and gross pathology were
evaluated. At 5 ppm, there was some slight decrease in weight gain,
although the author did not consider this to be important. No compound-
related effects were reported in any other parameters measured except
ChE activity. At 1 ppm, plasma ChE was inhibited 13% and 18%, and
red blood cell ChE was inhibited 6% and 19% in males and females,
respectively. At 2 ppm, plasma and red blood cell ChE was comparable
to control levels in males, and was inhibited 13% in plasma and 15%
in red blood cells in females. At 5 ppm, ChE in plasma was inhibited
44% and 41%,and red blood cell ChE was inhibited 22% and 26% (females
and males, respectively). No brain ChE measurements were reported.
Based on the absence of significant (>20%) ChE inhibition at 1 or
2 ppm, a NOAEL of 2 ppm (0.05 mg/kg/day) is identified.
0 Hayes et al. (1982) administered fenamiphos (90% purity) in the diet
to CD albino mice (50/sex/dose) at dose levels of 0, 2, 10 or 50 ppm
for 18 months. Assuming that 1 ppm in the diet of mice is equivalent
to 0.15 mg/kg/day (Lehman, 1959), this corresponds to doses of 0, 0.3,
1.5 or 7.5 mg/kg/day. Following treatment, body weight, food con-
sumption, hematology and mortality were evaluated. Absolute brain
weights were decreased at 2 ppm (0.3 mg/kg/day) or greater. At 50 ppm
(7.5 mg/kg/day), there was a decrease in body weight. Based on these
data, a Lowest-Observed-Adverse-Effect-Level (LOAEL) of 2 ppm (0.3
mg/kg/day), lowest dose tested, was identified, but not a NOAEL.
0 Lo.ser (1972a) administered technical fenamiphos (78.8% purity) in the
diet of Wistar rats (40/sex/dose) for 2 years at dose levels of 0, 3,
10 or 30 ppm a.i. Assuming that 1 ppm in the diet of rats is equiva-
lent to 0.05 mg/kg/day (Lehman, 1959), this corresponds to doses of
0, 0.15, 0.5 or 1.5 mg/kg/day. Untreated controls (50 males, 60
females) were run concurrently. Following treatment, body weight,
food consumption, hematology, urinalysis, plasma and erythrocyte ChE
activity, gross pathology and histopathology were evaluated. At the
highest dose (30 ppm), a slight increase in female mortality (38%
versus 29% in controls) was noted, but the author did not consider
this significant. Ihere were statistically significant (p <0.05)
increases in thyroid gland and lung weights in females and in heart
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Fenamiphos August, 1987
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weight in males. No compound-related effects were observed in any of
the other parameters measured except an inactivation of plasma and
erythrocyte ChE. At 10 ppm, ChE was decreased by 18 to 41%, and at
30 ppm, ChE was decreased by 28 to 60%. No brain ChE measurements
were reported. Based on ChE inhibition, the author identified a NOAEL
of 3 ppm (0.15 mg/kg/day). Based on organ weight changes, the NOAEL
was 10 ppm (0.5 mg/kg/day).
0 In chronic feeding studies by Loser (1972b), beagle dogs (four/sex/dose)
were administered technical fenamiphos (78.8% purity) in the feed for
2 years at 0, 0.5, 1, 2, 5 or 10 ppm active ingredient. Assuming
that 1 ppm in the diet of dogs is equivalent to 0.025 mg/kg/day (Lehman,
1959), this corresponds to doses of 0, 0.013, 0.025, 0.050, 0.125 or
0.250 mg/kg/day. Following treatment, no compound-related effects
were observed on appearance, general behavior, food consumption,
clinical chemistry, hematology, gross pathology or histopathology at
any dose tested. Plasma and erythrocyte ChE levels were inhibited
about 26% at 2 ppm, about 21 to 57% at 5 ppin and about 32 to 51% at
10 ppm. Cholinesterase was not inhibited at 1 ppm (0.025 mg/kg/day)
or below. Based on ChE inhibition, this study identified a NOAEL of
1 ppm (0.025 mg/kg/day) and a LOAEL of 2 ppm (0.05 mg/kg/day).
Reproductive Effects
0 In a three-generation study conducted by Loser (1972c), FB30 rats
(10 males or 20 females/dose) were fed technical fenamiphos (78.8%)
in the diet at dose levels of 0, 3, 10 or 30 ppm active ingredient.
Assuming that 1 ppm in the diet of rats is equivalent to 0.05 mg/kg/day
(Lehman, 1959), this corresponds to doses of 0, 0.15, 0.5 or 1.5
mg/kg/day. Fertility, lactation performance, pup development and
parental and litter body weights were evaluated. No compound-related
effects were observed in any parameter in animals exposed to 10 ppm
(0.5 mg/kg/day) or less. At 30 ppm (1.5 mg/kg/day), one male of the
F2b generation showed a lower body weight gain than the untreated
controls, but there were no differences in body weight gain in any
other generation. Based on these data, a reproductive NOAEL of 30
ppm (1.5 mg/kg/day) was identified.
Developmental Effects
MacKenzie et al. (1982) administered fenamiphos (88% a.i. by gavage
to pregnant New Zealand white rabbits (20/dose) at dose levels of 0,
0.1, 0.3 or 1.0 mg/kg/day on days 6 to 18 of gestation. Following
treatment, there was a decrease in maternal body weight at 0.3 mg/kg/day
or above. At the 1,0-mg/kg/day level, eight dead pups and seven late
resorptions were reported, and fetal weight was depressed. A signifi-
cant (p <0.05) increase in the incidence of chain-fused sternebrae
was also observed at 1.0 mg/kg. Based on maternal body weight, a
NOAEL of 0.1 mg/kg was identified. Based on fetotoxicity and terato-
genicity, a NOAEL of 0.3 mg/kg/day was identified.
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Fenamiphos August, 1987
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Mutagenicity
0 Herbold (1979) reported that fenamiphos was not mutagenic in Salmonella
typhimurium (TA 1535, 1537, 98 or 100) up to 2,500 ug/plate, either
with or without activation.
0 In a dominant lethal test with male mice (Herbold and Lorke, 1980),
acute oral doses of 5 mg/kg did not produce mutagenic effects.
Carcinogenicity
0 Hayes et al. (1982) administered fenamiphos (90% purity) for 18 months
in the diet to CD albino mice (50/sex/dose) at dose levels of 0, 2, 10
or 50 ppm (0, 0.3, 1.5 or 7.5 mg/kg/day). Based on gross and histo-
pathologic examination, neoplasms in various tissues and organs were
similar in type, organization, time of occurrence and incidence in
control and treated animals.
0 Loser (1972a) administered technical fenamiphos (78.8% purity) in the
diet of Wistar rats (40/sex/dose) for 2 years at dose levels of 3, 10
or 30 ppm active ingredient. Assuming that 1 ppm in the diet of rats
is equivalent to 0.05 mg/kg/day (Lehman, 1959), this corresponds to
doses of 0.15, 0.5 or 1.5 mg/kg/day. Untreated controls (50 males,
60 females) were run concurrently. No evidence of Carcinogenicity
was detected either by gross or histological examination.
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.
The 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, 100 or 1,000), in
accordance with NAS/ODW guidelines.
L/day = assumed daily water consumption by a child
(1 L/day) or an adult (2 L/day).
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Fenamiphos August, 1987
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One-day Health Advisory
No information was found in the available literature that was suitable
for determination of the One-day HA value for fenamiphos. It is therefore
recommended that the Ten-day HA value for the 10-kg child of 0.009 mg/L (9 ug/L,
calculated below) be used at this time as a conservative estimate of the
One-day HA value.
Ten-day Health Advisory
The study by MacKenzie et al. (1982) has been selected to serve as the
basis for determination the Ten-day HA value for fenamiphos. In this study,
pregnant rabbits (20/dose) were administered technical fenamiphos (88% purity)
by gavage at dose levels of 0, 0.1, 0.3 or 1.0 mg/kg on days 6 through 18 of
gestation. A decrease in maternal body weight was observed in animals dosed
with 0.3 mg/kg/day or above. No maternal toxicity was reported at 0.1 mg/kg/day.
No fetotoxicity or teratogenic effects were observed at 1.0 mg/kg or less or
0.3 mg/kg or less, respectively. Chain fusion of sternebrae were observed in
the 1.0 mg/kg group. Based on maternal effects, a NOAEL of 0.1 mg/kg/day was
identified.
Using a NOAEL of 0.1 mg/kg/day, the Ten-day HA for a 10-kg child is
calculated as follows:
Ten-day HA = (0'1 mg/kg/day) (10 kg) (0.88) = 0>009 /L (9 „ }
(100) (1 L/day)
where:
0.1 mg/kg/day = NOAEL, based on absence of maternal or fetal toxicity
in rabbits exposed to fenamiphos via gavage on days
6 through 18 of gestation.
1 0 kg = assumed body weight of a child.
0.88 = correction factor to account for 88% active ingredient
in administered doses.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
1 L/day = assumed water consumption of a child.
Longer-term Health Advisory
The study by Loser (1970) has been selected to serve as the basis for
determination of the Longer-term HA value for fenamiphos. In this study,
beagle dogs (two/sex/dose) were fed technical fenamiphos (99.4% purity) in
the diet at dose levels of 0, 1, 2 or 5 ppm (0, 0.025, 0.05 or 0.125 mg/kg/day)
for 3 months. No effects were detected on body weight, food consumption,
clinical chemistry, urinalysis and gross pathology. The only effect observed
was inhibition of plasma and erythrocyte ChE activity at the 5-ppm dose
level (0.125 mg/kg/day). No significant effect was seen at 2 ppm or less
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Fenamiphos August, 1987
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(0.05 mg/kg/day), which was identified as the NOAEL. The 90-day study in
F344 rats by Mobay Chemical Corporation (1983) identified a NOAEL of 1 ppm
(0.05 mg/kg/day), but this was not considered, since it was the highest dose
tested and a LOAEL was not identified. The study by Loser and Kimmerle
(1968) identified a NOAEL of 0.2 mg/kg/day in rats, but this was not chosen,
since available data (Loser et al., 1972a,b) suggest that the rat is less
sensitive than the beagle dog.
Using a NOAEL of 0.05 mg/kg/day, the Longer-term HA for a 10-kg child is
calculated as follows:
Longer-term HA = (0.05 mg/kg/day) (10 kg) = Oi005 /L (5 /L)
(100) (1 L/day)
where:
0.05 mg/kg/day = NOAEL, based on absence of significant cholinesterase
inhibition in dogs exposed to fenamiphos via the diet
for 3 months.
10 kg = assumed body weight of a child.
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 by a child.
The Longer-term HA for a 70-kg adult is calculated as follows:
Longer-term HA = (.°'05 mg/kg/day) (70 kg) = 0>01Q /L (1Q /L)
(100) (2 L/day)
where:
0.05 mg/kg/day = NOAEL, based on absence of significant cholinesterase
inhibition in dogs exposed to fenamiphos via the diet
for 3 months.
70 kg = assumed body weight of an adult.
100 = uncertainty factor, chosen in accordance with NAS/COW
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
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
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Fenamiphos August, 1987
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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. 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.
The study by Loser (1972b) has been selected to serve as the basis for
determination of the Lifetime HA value for fenamiphos. In this study, dogs
(four/sex/dose) were fed technical fenamiphos (78.8% purity) in the diet for
2 years at dose levels of 0, 0.5, 1, 2, 5 or 10 ppm active ingredient (0,
0.013, 0.025, 0.05, 0.125 or 0.25 mg/kg/day). The only effect detected was
inhibition of plasma and erythrocyte cholinesterase at dose levels of 2, 5 or
10 ppm (0.05, 0.125 or 0.25 mg/kg/day). The NOAEL identified in this study
was 1 ppm (0.025 mg/kg/day). The chronic studies in rats by Loser (1972a)
and by Hayes et al. (1982) were not chosen, since the data indicate the rat
is less sensitive than the dog.
Using a NOAEL of 0.025 mg/kg/day, the Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (0.025 mg/kg/day) = Q.00025 mg/kg/day
(100)
where:
0.025 mg/kg/day = NOAEL, based on absence of cholinesterase inhibition
in dogs exposed to technical fenamiphos via the diet
for 2 years.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = 0-00025 mg/kg/day) (70 kg) = 0.009 mg/day (9 ug/L)
(2 L/day)
where:
0.00025 mg/kg/day = RfD.
70 kg = assumed body weight of an adult.
2 L/day = assumed daily water consumption of an adult.
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Fenamiphos August, 1987
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Step 3: Determination of the Lifetime Health Advisory
Lifetime HA = (0.009 mg/L) (20%) = 0.0018 mg/L (1.8 ug/L)
where:
0.009 mg/L = DWEL.
20% = assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
0 No evidence of carcinogenic potential was detected in chronic feeding
studies in rats (Loser, 1972a) or mice (Hayes et al., 1982).
0 The International Agency for Research on Cancer has not evaluated the
carcinogenic potential of fenamiphos.
° Applying the criteria described in EPA's guidelines for assessment of
carcinogenic risk (U.S. EPA, 1986), fenamiphos may be classified in
Group D: not classified. This category is for substances with
inadequate animal evidence of carcinogenicity.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 Residue tolerances have been established for fenamiphos and its
cholinesterase-inhibiting metabolites in or on various agricultural
commodities at 0.02 to 0.60 ppm based on an ADI for fenamiphos
of 0.0025 mg/kg/day (U.S. EPA, 1985).
0 The World Health Organization (WHO) calculated a TADI of 0.0003
nig/kg/day for fenamiphos (Vettorazzi and Van den Hurk, 1985).
VII. ANALYTICAL METHODS
0 There is no standarized method for the determination of fenamiphos
in water samples. A procedure has been reported for the estimation
of fenamiphos and other pesticides in foods and feeds (FDA, 1979).
This procedure involves extraction and isolation in an organic phase/-
the extract is then dried and concentrated, and an aliquot of the
concentrated organic phase is injected into a gas chromatograph
equipped with a phosphorus-selective detector.
VIII. TREATMENT TECHNOLOGIES
0 No information was found in the available literature on treatment
technologies used to remove fenamiphos from contaminated water.
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Fenamiphos August, 1987
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IX. REFERENCES
Church, D.D.* 1970. Bay 68138 — leaching, runoff, and water stability.
Report No. 26849. Unpublished study received May 27, 1970 under OF0982;
submitted by Chemagro Corp., Kansas City, MO; CDL:091690-H. MRID 00067117.
Crawford, C., and R. Anderson.* 1973. The eye and skin irritancy of Nemacur
3 Ibs/gal spray concentrate to rabbits. Report No. 37549. Unpublished
study. MRID 00119227.
Dime, R.A., C.A. Leslie and R.J. Puhl.* 1983. Photodecomposition of Nemacur
in aqueous solution and on soil. Report No. 86171. Mobay Chemical Corp.
1983. Supplement No. 4 to brochure entitled: Nemacur: The effects on
the environment — environmental chemistry (dated Feb. 1, 1973). Document
No. AS83-2611. Compilation; unpublished study received Dec. 9, 1§83
under 3125-236; CDL:251891-A. MRID 00133402.
DuBois, K.P., M. Flynn and F. Kinoshita.* 1967. The acute toxicity and anti-
cholinesterase action of Bayer 68138. Unpublished study. MRID 00082807.
FDA. 1979. Food and Drug Administration. Pesticide analytical manual.
Revised June 1979.
Green, R., C. Lee and W. Apt.* 1982. Processes affecting pesticides and
other organics in soil and water systems: Assessment of soil and
pesticide properties important to the effective application of nematicides
via irrigation. Hawaii contributing project to Western Regional Research
Project W-82. Unpublished study. MRID 00154533.
Gronberg, R.R.* 1969. The metabolic fate of (Bay 68138), (Bay 68138 sulfoxide),
and (Bay 68138 sulfone) by white rats. Report No. 26759. Unpublished
study. MRID 00052527.
Gronberg, R.R., and S.H. Atwell.* 1980. Leaching of Nemacur residues in
Florida sand. Report No. 66409. Rev. Unpublished study received Aug. 28,
1980 under 3125-236; submitted by Mobay Chemical Corp., Kansas City, MO;
CDL:243126-Y. MRID 00045607.
Hayes, R.H., D.W. Lamb and D.R. Ma'llicoat. * 1982. Technical fenamiphos
oncogenicity study in mice. Report No. 3037. Unpublished study.
MRID 00098614.
Herbold, B.* 1979. Nemacur: Salmonella/microsome test for detection of
Point-mutagenic effects: Report No. 8730; 82210. Unpublished study.
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Herbold, B., and D. Lorke.* 1980. SRA 3386: Dominant lethal study on male
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study. MRID 00086981.
Kimmerle, G., and D. Lorke.* 1970. Bay 68138: Subchronic neurotoxicity
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MRID 00082105.
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Fenamiphos August, 1987
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Lehman, A.J. 1959. Appraisal of the safety of chemicals in foods, drugs and
cosmetics. Assoc. Food Drug Off.
Loser, E.* 1970. Bay 68138: Subchronic toxicological studies on dogs (three
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Loser, E.* 1972a. Bay 68138: Chronic toxicological studies on rats (two-year
feeding experiment). Report No. 3539; Report No. 34344. Unpublished
study. MRID 00038490.
Loser, E.* 1972b. Bay 68138: Chronic toxicological studies on dogs (two-year
feeding experiment). Report No. 3561; Report No. 34345. Unpublished
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Loser, E.* 1972c. Bay 68138: Generation studies on rats. Report No. 3424;
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Loser, E., and G. Kimmerle.* 1968. Bay 68138: Subchronic toxicological study
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MacKenzie, K., S. Dickie, B. Mitchell et al.* 1982. Teratology study with
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McNamara, F.T., and C.M. Wilson.* 1981. Behavior of Nemacur in buffered
aqueous solutions. Report No. 68582. Unpublished study received July 23,
1981 under 3125-236; submitted by Mobay Chemical Corp., Kansas City, MO;
CDL:245613-A. (00079270).
Meister, R., ed. 1983. Farm chemicals handbook. Willoughby, OH: Meister
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Mobay Chemical Corporation.* 1983. Combined chronic toxicity/oncogenicity
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NIOSH. 1985. National Institute for Occupational Safety and Health. Registry
of Toxic Effects of Chemical Substances (RTECS). National Library of
Medicine Online File.
Tweedy, E.G., and L.D. Houseworth.* 1980. Leaching of aged Nemacur residues
in sandy loam soil. Report No. 40506. Unpublished study received Aug. 28,
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incidents involving fenamiphos. Pesticide Incident Monitoring System.
Report No. 208. Washington, DC: U.S. Environmental Protection Agency.
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Regulations. 40 CFR 180.349, p. 324. July 1, 1985.
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Fenamiphos August, 1987
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U.S. EPA. 1986. U.S. Environmental Protection Agency. Guidelines for
carcinogen risk assessment. Fed. Reg. 51(1 85): 33992-34003.
September 24.
Vettorazzi, G., and G.W. Van den Hurk. 1985. Pesticides reference index,
JMPR 1961-1984. p. 10.
*Confidential Business Information.
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