820K88128 August' 1987
DRAFT
MCPA
(4-Chloro-2-Methylphenoxy)-Acetic Acid
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 ^hat
any one of these models is able 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 AND PROPERTIES
CAS Mo. 94-74-6
Structural Formula
OCH2COOH
(4-Chloro-2-methyl phenoxy) -acetic acid
Synonyms
0 MCPA; MCP; Agroxone; Hormotuho; Metaxon.
Uses
0 MCPA is a hormone-type herbicide used to control annual and perennial
weeds in cereals, grassland and turf (Hayes, 1982).
Properties (CHEMLAB, 1985; Meister, 1983)
Chemical Formula CgHgC^Cl
Molecular Weight 200.63
Physical State (25°C) Light brown solid
Boiling Point
Melting Point 118 to 119°C
Vapor Pressure (25°C)
Density (25°C) 1.56
Water Solubility 825 mg/L (room temperature)
Log Octanol/Water Partition 2.07 (calculated)
Coefficient
Taste Threshold
Odor Threshold
Conversion Factor
Occurrence
0 MCPA has been found in 4 of 12 surface water samples analyzed and in
none of 99 ground water samples (STORET, 1987). Samples were collected
at 8 surface water locations and 97 ground water locations. MCPA was
found only in California. The 85th parcentile of all nonzero samples
was 0.54 ug/L in surface water, and the maximum concentration found
was 0.54 ug/L.
Environmental Fate
0 MCPA is not hydrolyzed at pH 7 and 34 to 35°C (Soderquist and Crosby,
1974, 1975). MCPA in aqueous solution (pH 8.3) has a photolytic
half-life of 20 to 24 days in sunlight. With fluorescent light, MCPA
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in aqueous solution (pH 9.8) produced three minor (less than 10%)
photolysis products: 4-chloro-2-methyl-phenol, 4-chloro-2-formylphenol
and ^-cresol in 71 hours (Soderquist and Crosby, 1974, 1975).
MCPA is degraded more rapidly (1 day) in soils containing less than
10% organic matter than in soil containing higher levels (3 to 9 days)
(Torstensson, 1975). This may be due to adsorption to the soil
organic matter. MCPA, when applied a second time to soil, is degraded
twice as fast (6 to 12 days) as it is after one application (15 to 28
days). Persistence does not depend greatly upon the soil type (Loos
et al., 1979).
Unlabeled MCPA in rice paddy water under dark conditions is totally
degraded by aquatic microorganisms in 13 days (Soderquist and Crosby,
1974, 1975).
MCPA would be expected to leach readily in most soils. Phytotoxic
levels of MCPA leached 30 cm in a sandy soil column eluted with 50 cm
of water (Herzel and Schmidt, 1979). Using soil thin-layer chromato-
graphic techniques, MCPA was mobile (Rf 0.6 to 1.0) in calcium
montmorillonite clay (Helling, 1971) and in sandy loam, silt loam,
and silty clay loam soils (Helling and Turner, 1968). Mobility
increases as organic matter content decreases, possibly due to
adsorption of MCPA to this soil component.
MCPA does not volatilize from aqueous solution (pH 7.0) heated for
13 days at 34 to 35°C (Soderquist and Crosby, 1974, 1975).
Using bioassays, MCPA appears to dissipate fairly rapidly (3 to 7
weeks) from soil treated with levels of 0.75 to 1.5 ppm for 6 to 19
previous years (DeRose, 1946; Fryer and Kirkland, 1970; Torstensson
et al., 1975). An initial application of MCPA may require up to 20
weeks for complete dissipation. In another study, MCPA dissipated
to nondetectable levels from sandy and silt loam soils in 30 to 60
days (Suzuki, 1977).
In the aquatic environment, MCPA disipates rapidly (14 to 32 days)
in water, but residue levels in the flooded soil remain unchanged
(Soderquist and Crosby, 1974, 1975; Sokolov et al., 1974, 1975).
A common metabolite, 5-chloro^o-cresol, is formed at low levels
(1.3% or less) within 1 day of treatment. Frank et al. (1979) detected
MCPA residues (1.1 to 1000 ppb) in 2 of 237 wells in Ontario, Canada,
between 1969 and 1978.
In the forest ecosystem, MCPA remains in soil (0 to 3 cm) and leaf
litter at 0.7 and 32 ppm, respectively, 10 months after application
at 2.5 kg active ingredient per hectare (ai/ha) (Eronen et al.,
1979). MCPA residues in moss decline to 7% of the initial level
within 40 days. Residues in soil (3 to 15 cm deep) are not detectable
after 40 days.
MCPA has not been found in U.S. ground water.
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III. PHARMACOKINETICS
Absorption
0 No information on the absorption of MCPA was found in the available
literature.
Distribution
0 Elo and Yltalo (1979) treated rats with 8 mg of 14c-MCPA [98% active
ingredient (a.i.)] intravenously and measured the distribution of
radioactivity in nine tissues 1.5 hours after treatment. Highest
levels were found in plasma, kidney, lung, liver and heart with
lesser amounts found in brain/cerebrospinal fluid (CSF), testis and
muscle. Prior treatment of rats with MCPA (intravenous injections
of 25 to 500 mg/kg 3 hours before administration of radiolabeled
compound or chronic exposure to 500 or 2,500 mg/L in drinking water)
lead to decreased levels of 14C-MCPA in the plasma and kidney and
increased levels in brain/CSF.
0 Elo and Yltalo (1977) treated rats with 8 mg of 14C-MCPA (purity not
specified) intravenously and measured the distribution of radioactivity
in brain, CSF, muscle, liver and kidney 1.5 to 120 hours after treat-
ment. Prior treatment of rats with MCPA (subcutaneous injections of
250 or 500 mg/kg) caused a decrease in the amount of radioactivity
found in the plasma. Increased levels were found in other tissues
with the largest increases found in the CSF (39- to 67-fold) and
brain (11- to 18-fold).
Metabolism
e MCPA is metabolized by the liver. Stimulation of microsomal oxidation
by phenobarbital increases the rate of MCPA breakdown (Buslovich et al.,
1979). Gaunt and Evans (1961) found that 5-chloro-methyl-catechol is
one of the metabolites of MCPA (Hattula et al., 1979).
Excretion
In studies by Fjeldstad and Wannag (1977), four healthy human volun-
teers each ingested a dose of 5 mg of MCPA (purity not specified).
Approximately 50% (2.5 mg) of the dose was detected in the urine
within several days. Urinary levels were not detectable on the fifth
day following exposure.
Rats treated orally with MCPA (purity not specified) excreted nearly
all of the MCPA during the first 24 hours after intake (90% in urine
and 7% in feces) (Elo, 1976).
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IV. HEALTH EFFECTS
Humans
Short-term Exposure
0 Palva et al. (1975) reported- one case of MCPA (purity not specified)
exposure (dose and duration not specified) in a farmworker involved in
spraying operations. Exposure resulted in reversible aplastic anemia
as well as muscular weakness, hemorrhagic gastritis and slight signs
of liver damage that were later followed by pancytopenia of all of
the myeloid cell lines. In a followup study in the exposed farmer,
Timonen and Palva (1980) reported the occurrence of acute myelomono-
cytic leukemia.
Long-term Exposure
0 No information on the human health effects of chronic exposure to
MCPA was found in the available literature.
Animals
Short-term Exposure
0 Reported acute oral LD50 values for MCPA (purity not specified) in
mice and rats are 550 mg/kg and 700 mg/kg, respectively (RTECS, 1985).
0 Gurd et al. (1965) reported an acute oral LD50 value for MCPA (purity
not specified) of 560 mg/kg in mice.
0 Elo et al. (1982) showed that MCPA (sodium salt; 99% a.i.) causes a
selective damage of the blood-brain barrier. These authors observed
that the penetration of intravenous tracer molecules such as 14c-MCPA,
14C-PABA, 14C-sucrose, 14C-antipyrine and iodinated human albumin
(125i_HA) in the brain and CSF of MCPA-intoxicated rats (200 to
500 mg/kg, sc) was increased compared to controls. The tissue-plasma
ratios of 14C-sucrose, 14C-antipyrine and 125I-HA treated rats were
also increased in the brain and CSF of intoxicated animals, but the
increases were less pronounced than those of 14C-MCPA or 14C-PABA.
0 In oral studies by Vainio et al. (1983), Wistar rats administered an
ester of MCPA (purity not specified) (0, 100, 150 or 200 mg/kg/day),
5 days per week for 2 weeks, showed hypolipidemia and peroxisome
proliferation in the liver. A Lowest-Observed-Adverse-Effect-Level
(LOAEL) of 100 mg/kg was identified.
Dermal/Ocular Effects
0 Raltech (1979) reported acute dermal LDso values for MCPA (purity not
specified) in rabbits of 4.8 g/kg for males and 3.4 g/kg for females.
0 In acute dermal studies conducted by Verschuuren et al. (1975), an
aqueous paste of MCPA (80.6% a.i.) (0.5 g) was applied to the abraded
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skin of five chinchilla rabbits. Slight erythema resulted; the
skin became sclerotic after 5 to 6 days and healed by 12 days.
0 In subacute dermal studies, Verschuuren et al. (1975) applied an
aqueous paste of MCPA (80.6% active ingredient; 0, 0.5, 1.0 or 2.0 g)
five times weekly for 3 weeks to the shaved skin of rabbits. Slight
to moderate erythema occurred at all dose levels, and elasticity of
the skin was decreased. The effects subsided at 2 weeks post-treatment.
Weight loss was observed at all dose levels. High mortality and
histopathological alterations were observed in the liver, kidneys,
spleen and thymus at the 1.0- and 2.0-g dose levels.
Long-term Exposure
0 Verschuuren et al. (1975) administered MCPA (80.6% a.i.) in the diet
for 90 days to SPF weanling rats (10/sex/dose) at levels of 0, 50,
400 or 3,200 ppm. 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
about 0, 2.5, 20 or 160 mg/kg/day. Following treatment, growth, food
intake, mortality, hematology, blood and liver chemistry, organ
weights and histopathology were measured. No compound-related effects
were reported for any of these parameters except for growth retard-
ation and elevated relative kidney weights at 400 ppm (20 mg/kg/day)
or more. A No-Observed-Adverse-Effect-Level (NOAEL) of 50 ppm
(2.5 mg/kg/day) and a LOAEL of 400 ppm (20 mg/kg/day) were identified.
* Holsing and Kundzin (1970) administered MCPA (considered to be 100%
a.i.) in the diet of rats (10/sex/dose) for 3 months. Doses were
reported as 0, 4, 8 or 16 mg/kg/day; the concentration in the diet
was not specified. Following treatment, no compound-related effects
were observed in the physical appearance, behavior, growth, food
consumption, survival, clinical chemistry, organ weights, organ-to-
body weight ratios, gross pathology or histopathology at any dose
tested, except for increases in kidney weight in males at 16 mg/kg/day.
A NOAEL of 8 mg/kg/day and a LOAEL of 16 mg/kg/day were identified
by this study.
0 Holsing and Kundzin (1968) administered oral doses of MCPA to rats at
dose levels of 0, 25, 50, and 100 mg/kg/day for 13 weeks. Cytopatho-
logical changes in the liver and kidneys were observed at all doses.
Kidney effects included focal hyperplasia of tht< eptithelial lining,
interstitial nephritis, tubular dilation and/or hypertrophy. A LOAEL
of 25 mg/kg/day (the lowest dose tested) is identified by this study.
0 Reuzel and Hendriksen (1980) administered MCPA (94% a.i.) in feed to
dogs in two separate 13-week studies. Dosing regimens of 0, 3, 12 or
48 mg/kg/day, and 0, 0.3, 1 or 12 mg/kg/day, respectively, were
employed. Decreased kidney and liver function, characterized by
increases in blood urea, SGPT and creatinine were observed at doses
as low as 3 mg/kg/day. Low prostatic weight and mucopurulent conjunc-
tivitis were observed at higher doses. A NOAEL of 1 mg/kg/day and a
LOAEL of 3 mg/kg/day were identified by these studies.
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0 Hellwig (1986) administered oral doses of MCPA (95% a.i.) to dogs at
doses of 0, 6, 30, or 150 ppm for 1 year. Assuming that 1 ppro in the
diet of dogs is equivalent to 0.025 mg/kg (Lehman, 1959), this corre-
sponds to doses of 0, 0.15, 0.75 or 1.5 mg/kg/day. Renal toxicity
was observed at the two highest doses and was characterized by elevated
serum levels of creatinine, urea and potassium, coloration of the
kidneys and increased storage of pigment in the renal tubules. A
NOAEL of 0.15 mg/kg/day and a LOAEL of 0.75 mg/kg/day were identified
by this study.
0 Holsing (1968) administered oral doses of MCPA (considered to be
100% a.i.) (0, 25, 50 or 75 mg/kg/day) to beagle dogs (three/sex/dose)
for 13 weeks. Histopathological changes and alterations in various
hematologic and biochemical parameters indicative of bone marrow,
liver and kidney damage were observed at all dose levels. The
hematological findings included decreased hematocrit, hemoglobin and
erythrocyte counts. Several dogs had elevated blood urea nitrogen,
serum glutamic-pyruvic transaminase, serum-oxaloacetic transaminase,
alkaline phosphatase and serum bilirubin. Histopathological alterations
were seen in the liver, kidney, lymph nodes, testes, prostate and
bone marrow. All dogs of all three groups had various degrees of
hepatic, renal and bone marrow injury. A LOAEL of 25 mg/kg/day (the
lowest dose tested) was identified.
0 Gurd et al. (1965) administered technical MCPA (purity not specified)
in the feed to rats (five/sex/dose) for 7 months at dose levels of 0,
100, 400, 1,000 or 2,500 ppm. 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, 5, 20, 50 or 125 mg/kg/day. Following treatment, there
was a marked decrease in body weight gain at 1,000 ppm (50 mg/kg/day)
or 2,500 ppm (125 mg/kg/day), and some deaths occurred at 2,500 ppm
(125 mg/kg/day). At 400 ppm (20 mg/kg/day) or greater, there was a
reduction in numbers of red blood cells, hemoglobin content and
hematocrit. Relative kidney weights were increased at 100 ppm
(5 mg/kg/day), but no effects on body weight were evident. No
histopathological changes were reported at any dose level tested.
A LOAEL of 5 mg/kg/day (the lowest dose tested) was identified.
Reproductive Effects
0 No effects on reproduction were found in rats exposed to doses of
0, 50, 150, or 450 ppm MCPA (95% a.i.) in the diet over a period of
two generations (MacKenzie, 1986). Assuming that 1 ppm in the diet
of rats corresponds to 0.05 mg/kg/day (Lehman, 1959), this corresponds
to doses of 0, 2.5, 7.5 or 15 mg/kg/day. Body weight depression was
observed in the F-\ and F2 generations at the two highest doses. A
NOAEL of 15 mg/kg/day was identified for reproductive function, and
a NOAEL of 2.5 mg/kg/day was identified for fetoxtoxicity (depressed
weight gain).
Developmental Effects
0 Irvine et al. (1980) administered MCPA (purity not specified) (0, 5,
12, 30 or 75 mg/kg/day) by gavage to rabbits (15 to 18/dose) on days
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6 to 18 of gestation. No fetotoxicity or teratogenicity was observed
at any dose level tested. Body weights of the does were markedly
reduced in the 75 mg/kg/day dosage group. A fetal NOAEL of 75 mg/kg/day
and a maternal NOAEL of 30 mg/kg/day were identified.
0 Irvine (1980) administered MCPA (purity not specified) (0, 20, 50 or
125 mg/kg/day) by gavage to pregnant CD rats (16 to 38/dose) on days
6 to 15 of gestation. No maternal or fetal toxicity or teratogenic
effects were observed. A NOAEL of 125 mg/kg/day (the highest dose
tested) was identified.
0 Palmer and Lovell (1971) administered oral doses of MCPA (75% a.i.;
0, 5, 25 or 100 mg/kg/day of the active ingredient) to mice (20/dose)
on days 6 to 15 of gestation. Dams were monitored for pregnancy rate,
body weight, and gross toxicity; no significant effects were observed.
At 100 mg/kg/day, fetal weights were significantly reduced and there
was delayed skeletal ossification. A NOAEL of 25 mg/kg/day and a
LOAEL of 100 mg/kg/day based on fetal weights were identified.
Mutagenicity
0 Moriya et al. (1983) reported that MCPA (purity not specified) (5,000
ug/plate) did not produce mutagenic activity in Salmonella typhimurium
(TA 100, TA 98, TA 1535, TA 1537, TA 1538) and in Escherichia coli
(WP2 her) either with or without metabolic activation.
0 In studies conducted by Magnusson et al. (1977), there were no
effects on chromosome disjunction, loss or exchange in Drosophila
fed MCPA (250 or 500 ppm).
0 In studies by Linnainmaa (1984), no increases were observed in the
frequency of sister chromatid exchange (SCE) in blood lymphocytes
from rats intragastrically administered MCPA (purity not specified)
at 100 mg/kg/day for 2 weeks. A slight increase in SCE was observed
in bone marrow cells from Chinese hamsters given daily oral doses of
100 mg/kg for 2 weeks. In Chinese hamster ovarian cell cultures,
SCE was slightly increased following treatment with MCPA (10~5, 10~4,
10-3^ 1 hour) with and without activation.
Carcinogenicity
0 No information on the potential carcinogenicity of MCPA was found in
the available literature. However, MCPA stimulates liver peroxisomal
proliferation, which has been implicated in carcinogenicity (Vainio
et al., 1983).
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;
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HA = (NOAEL or LOAEL) x (BW) = mg/L ( ug/L)
(UF) x ( L/day)
where:
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effeet-Level
in mg/kj bw/day.
BW = assumed body weight of a child (10 kj) 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 of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
No information was found in the available literature that was suitable
for determination of the One-day HA value for MCPA. It is therefore recom-
mended that the Longer-term HA value for a 10-kj child (0.1 mg/L, calculated
below) be used at this time as a conservative estimate of the One-day HA value.
Ten-day Health Advisory
No information was found in the available literature that was suitable
to serve as the basis for determining the Ten-day HA value for MCPA. Several
reproductive/teratology studies have been performed in which rats or rabbits
have been given oral doses of MCPA for acute duration (Irvine, 1980; Irvine
et al., 1980; Palmer and Lovell, 1971; MacKenzie, 1986). The only signs of
maternal toxicity observed in these studies was a reduction in body weight in
rats exposed to 75 mg/kj (Irvine, 1980). Estimates of maternal NOAELs range
from 30 to 125 mg/kj/day (Irvine, 1980; Irvine et al, 1980). Fetotoxicity
has been observed at dose levels as low as 7.5 mg/kj/day (MacKenzie, 1986).
The toxicity of MCPA from acute exposure has not been well characterized. It
is therefore recommended that the Longer-term HA value for a 10-kg child of
(0.1 mg/L, calculated below) be used at this time as a conservative estimate
of the Ten-day HA value.
Longer-term Health Advisory
Evidence of renal dysfunction has been observed in both 13-week (Reuzel and
Hendriteen, 1980; Holsing, 1968) and 1-year (Hellwig, 1986) feeding studies in
beagle dogs and serves as the basis for the Longer-term HA. In subchronic studies
changes in blood urea and creatinine levels have been observed at doses of 25
mg/kj/day (Holsing, 1968) and 3 mg/kj/day (Reuzel and Hendriteen, 1986). Renal
toxicity is not unique to dogs and has been observed in rats after 90-day
exposure at dose levels of 20 mg/kj/day (Verschuuren et al., 1975) and 25
mg/kj/day (Holsing, 1968), The rat and dog may have similar sensitivities; a
conservative estimate of the NOAEL was obtained from the studies described by
Reuzel and Hendriteen (1980). In these studies, oral doses of 0, 3, 12 or 48
mg/kj/day, and 0, 0.3, 1 or 12 mg/kj/day, respectively, were administered to
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dogs for 13 weeks. Increases in blood urea, SGPT and creatinine levels were
observed at dose levels as low as 3 mg/Jq/day; low prostatic weight and
mucopurulent conjunctivitis were observed at higher dose levels. A NOAEL of
1 mg/kg/day was identified by these studies.
Using a NOA^L of 1 mg/Jq/day, the Longer-term HA for a 10-Jq child is
calculated as follows:
Longer-term HA = (1.0 mg/Jq/day) (10 Jq) = Q.10 mg/L (100 ug/L)
(100) (1 L/day)
where:
1.0 mg/Jq/day = NOAEL, based on the absence of renal effects in dogs
exposed to MCPA in the diet for 90 days.
1 0 Jq = 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 of a child.
The Longer-term HA for a 70-Jq adult is calculated as follows:
Longer-term HA = (1'° mg/Jq/day) (70 Jq) = Q%35 /L (350 ug/L)
(100) (2 L/day)
where:
1.0 mg/Jq/day = NOAEL, based on the absence of renal effects in dogs
exposed to MCPA in the diet for 90 days.
70 Jq = assumed body weight of an adult.
100 = uncertainty factor, chosen in accordance with NAS/ODW
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 drinJdng 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 IntaJe (ADI). The RfD is an esti-
mate of a daily exposure to the human population that is liJely to be without
appreciable ris k 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 Drin JcLng Water Equivalent Level
(DWEL) can be determined (Step 2). A DWEL is a medium-specific (i.e., drinJdng
water) lifetime exposure level, assuming 100% exposure from that medium, at
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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 chronic toxicity study in dogs (Hellwig, 1986) has been selected to
serve as the basis for the determination of the Lifetime HA. Beagle ,dogs were
exposed to 0, 6, 30 and 150 ppm (0.15, 0.75, or 3.75 mg/kg/day) for 1 year.
Renal toxicity was observed at the two highest doses and was characterized by
elevated serum levels of creatinine, urea and potassium, coloration of the
kidneys and increased storage of pigment in the renal tubules. A NOAEL of
0.15 mg/kg/day was identified, which is supported by the findings from
subchronic feeding studies. From 90-day feeding studies, NOAELs of 1 mg/kg/day
and 2.5 mg/kg/day have been identified for dogs (Reuzel and Hendriksen, 1980)
and rats (Verschuuren et al., 1975), based on the absence of effects on the
kidney seen at higher doses. In a 7-month feeding study, Gurd (1965) observed
increased kidney weight in rats exposed to doses as low as 5.0 mg/kg/day, the
lowest dose tested.
Using a NOAEL of 0.15 mg/kg/day, the Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (0.15 mg/kg/day) = 0.0005 mg/kg/day
(100) (3)
where:
0.15 mg/kg/day = NOAEL, based on the absence of kidney effects in
dogs exposed to MCPA in the diet for 1 year.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
3 = additional uncertainty factor, chosen in accordance
with U.S. EPA Office of Pesticide Programs (OPP)
policy to account for the incomplete database on
chronic toxicity.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.0005 mg/kg/day) (70 kg) = 0>018 mg/L (18 ug/L)
(2 L/day)
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MCPA August, 1987
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where:
0.0005 mg/kg/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 = (0.018 mg/L) (20%) = 0.0036 mg/L (3.6 ug/L)
where:
0.018 = DWEL.
20% = assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
0 No studies on the carcinogenic potential of MCPA were found in the
available literature.
0 The International Agency for Research on Cancer (IARC, T983) concluded
that the potential carcinogenicity of MCPA in both humans and laboratory!
animals was indeterminate.
0 Applying the criteria described in EPA's guidelines for assessment of
carcinogenic risk (U.S. EPA, 1986), MCPA 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 National Academy of Sciences has recommended an ADI of 0.00125
mg/kg/day and a Suggested-No-Adverse-Response-Level (SNARL) of
0.009 mg/L, based on a LOAEL of 1.25 mg/kg/day in a 90-day study in
rats (NAS, 1977).
0 Residue tolerances have been established for MCPA at 0.1 ppm in milk
and meat. Peed and forage residue tolerances range from 0.1 to
300 ppm (U.S. EPA, 1985a).
VII. ANALYTICAL METHODS
0 Analysis of MCPA is by a gas chromatographic (GC) method applicable
to the determination of certain chlorinated acid pesticides in water
samples (U.S. EPA, 1985b). In this method, approximately 1 liter of
sample is acidified. The compounds are extracted with ethyl ether
using a separatory funnel. The derivatives are hydrolized with
potassium hydroxide, and extraneous organic material is removed by
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a solvent wash. After acidification, the acids are extracted and
converted to their methyl esters using diazomethane as the derivatizing
agent. Excess reagent is removed, and the esters are determined by
electron-capture GC. The method detection limit has been estimated
at 249 ug/L for MCPA.
VIII. TREATMENT TECHNOLOGIES
0 Oxidation by ozone of 500 mg/L MCPA, after 50 to 80% disappearance
of initial compound, produced no identifiable degradation products
(Legube et al., 1981). This indicates that oxidation by ozone may
be a possible MCPA removal technique.
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MCPA August, 1987
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Confidential Business Information submitted to the Office of Pesticide
Programs.
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