820K89
101
DALAPON
Health Advisory -«•
Office of Drinking Water r *
U.S. Environmental Protection Agency~_
I. INTRODUCTION
-re
The Health Advisory (HA) Program, sponsored by the Office of Breaking
Water (ODW), provides information on the health effects, analytical aethod-
ology and treatment technology that would be useful in dealing with tehe
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 ^ofi the
population. .-. (r
: -f dŁ
Health Advisories serve as informal technical guidance to assist Federal,
State and local officials responsible for protecting public health -wjten
emergency spills or contamination situations occur. They are not torbe
construed as legally enforceable Federal standards. The HAs are subject to
change as new information becomes available. - ^rr
Health Advisories are developed for one-day, ten-day, long-er-tefcm
(approximately 7 years, or 10% of an individual's lifetime) and 1-ifeftime
exposures based on data describing noncarcinogenic end points of tojfeicity.
Health Advisories do not quantitatively incorporate any potential carcinogenic
risk from such exposure. For those substances that are known ojr probable
human carcinogens, according to the Agency classification schenfe fcGr<5up 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, im.easess
of the stated values. Excess cancer risk estimates may also be calculated
using the One-hit, Weibull, Logit or Probit models. There Is no atiEcent
understanding of the biological mechanisms involved in cancer to suggest that
any one of these models is able to predict risk more accurately than another.
Because each model is based on differing assumptions, the estimatesEthat are
derived can differ by several orders of magnitude.
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Dalapon
II. GENERAL INFORMATION AND PROPERTIES
CAS No. 75-99-0
Structural Formula
August, 1987
-2-
CH,CCI2COOH
(2,2-Dichloropropionic acid)
Synonyms
Dalapon (ANSI, BSI, WSSA), DPA, Basfapon and Basfapon B (discontinued
by BASF Wyandotte); Basfapon/Basfapon N, BH Dalapon and Crisapon
(Crystal Chemical Inter-America); Dalapon 85, Dalapon-Na, Ded-Weed
and Devipon (Devidayal); Dowpon, Dowpon M, Gramevin and Radapon (discon-
tinued by Dow); Revenge (Hopkins); Unipon (Heister, 1984).
Uses
9 Dalapon (2,2-dichloropropionic acid) is used as a herbicide in the
form of its sodium and/or magnesium salts to control grasses in crops,'
drainage ditches, along railroads and in industrial areas (U.S. EPA,
1984).
Properties (U.S. EPA, 1984)
Chemical Formula
Molecular Weight
Physical State (room temp.)
Boiling Point
Melting Point
Density (°C)
Vapor Pressure
Specific Gravity
Water Solubility (25°C)
Log Octanol/Water Partition
Coefficient
Taste Threshold
Odor Threshold
Conversion Factor
Occurrence
C3H4C1202
143 (acid form)
liquid
185 to 190°C
20°C
>800 mg/L
Dalapon has been found in none of the surface water or ground water
samples analyzed from 14 samples taken at 14 locations (STORET, 1987)
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Dalapon August, 1987
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Environmental Fate
0 The sodium salt of dalapon has been shown to hydrolize slowly in
water to produce pyruvic acid, and the rate of hydrolysis increases
with increasing temperature. After 175 hours, the extent of hydrolysis
at 25°C for 1%, 5% and 18% dalapon solutions was 0.41%, 0.61% and 0.8%,
respectively (Brust, 1953).
0 Hydrolysis of solutions of either dalapon or dalapon sodium salt is
accelerated at alkaline pH values. For example, hydrolysis of dalapon
sodium salt at 60°C was 20% complete in 30 hours at which time the
equilibrium pH was 2.3. In contrast, hydrolysis was 50% complete
in 30 hours when the pH was maintained at 12 during the experiment
(Tracey and Bellinger, 1958).
0 Based on reaction rate studies, Kenaga (1974) concluded that both
dalapon salt and dalapon would have chemical hydrolysis half-lives of
several months at temperatures less than 25°C and at initial solution
concentrations of less than 1%. Considering the more rapid rate of
microbial degradation, those authors concluded that it does not appear
that chemical hydrolysis of dalapon is a particularly significant
degradative pathway in soils.
0 Because of its high water solubility and lack of affinity for soil
particles, appreciable adsorption of dalapon on suspended or bottom
sediments is not expected in natural waters. Chemical degradation
and volatilization probably occur too slowly to account for substantial
loss of dalapon from water. Aquarium studies conducted by Smith et al.
(1972) provide evidence that volatility is not a route for significant
loss of dalapon from water.
0 Microbial degradation is by far the most important process affecting
the fate of dalapon in soil. Other processes which are of lesser
importance are adsorption, leaching and runoff, chemical degradation
and volatilization. Based on the light absorption characteristics of
aqueous solutions of sodium salts of dalapon, it has been concluded
that photodecomposition of dalapon in field applications is improbable
(Kearney et al., 1965).
0 Although dalapon is subject to hydrolysis under field conditions,
chemical degradation is considered to be very slow and is unlikely
to be an important factor in the dissipation of dalapon from soil.
Smith et al. (1957) and Brust (1953) demonstrated that dalapon and
its sodium salt can undergo hydrolysis to pyruvate and HC1.
0 Although the laboratory studies indicate that dalapon is a highly
mobile compound (Warren, 1954; Helling, 1971; Kenaga, 1974) and should
be readily leachable from soils, field data show that under many
practical conditions dalapon does not move beyond the first six-inch
depth of soil. This is probably because microbial action proceeds at
a faster rate than leaching under favorable conditions (Kenaga, 1974).
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Dalapon August, 1987
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* The microbia] degradation of dalapon in soil has been well established<
Thiegs (1955) compared the rates of degradation of dalapon in autoclaved
and non-autoclaved soils. The concentration of dalapon (59 ppm) in
the autoclaved soil did not change after incubation at 100°F for 1 week
while in the unsterilized soil, dalapon disappeared in 4 to 5 weeks
after one application and in 1 week after the second application of
50 ppm. Based on the observations that dalapon decomposition is
adversely affected by low soil moisture, low pH, temperatures below
20° to 25°C, and large additions of organic matter, Holstun and
Loomis (1956) concluded that dalapon degradation was a function of
microbiological activity.
III. PHARMACOKINETICS
Absorption
0 In both dogs and humans, orally administered dalapon is quickly excreted
in the urine. Dogs administered a single oral dose of 500 mg/kg
dalapon sodium salt excreted 65 to 70% of the administered dose in
48 hours (Hoerger, 1969). In a 60-day feeding study, dogs receiving
50 and 100 mg/kg of dalapon sodium salt excreted 25 to 53% of the
administered dose in the urine (Hoerger, 1969). 'Human subjects
consuming five successive daily oral doses of 0.5 mg of dalapon
sodium salt excreted approximately 50% of the administered dose over
an 18-day period (Hoerger, 1969). These data suggest that dalapon
is well absorbed from the gastrointestinal tract.
Distribution
0 Chronic oral administration of dalapon did not result in significant
bioaccumulation in either rats or dogs (Paynter et al., 1960). In both
rats and dogs, the highest levels of dalapon were found in the kidneys,
followed by the muscle and the fat (Paynter et al., 1960).
Metabolism
0 Although inadequate data are available to characterize dalapon
metabolism in humans, data in cattle (Redemann and Hanaker, 1959)
suggest that dechlorination may be involved in the metabolism of
dalapon.
Excretion
Available information suga^sts that at least 50% of orally admini-
stered dalapon is eliminated via the kidneys in dogs and humans
{Hoerger, 1969).
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IV. HEALTH EFFECTS
Humans
Short-term Exposure
0 No information on the short-term health effects of dalapon in humans
was found in the available literature.
Long-term Exposure
0 No information on the long-term health effects of dalapon in humans
was found in the available literature.
Animals^
Short-term Exposure
0 The sodium salt of dalapon is relatively nontoxic, with an oral V^Q
ranging from 3,860 mg/kg in the female rabbit to 7,570 mg/kg in the
female rat (Paynter et al., 1960).
Dermal/Ocular Effects
0 Concentrated .sodium dalapon solutions have been found to be irritating
to the skin and eyes of rabbits (Paynter et al., 1960).
Long-term Exposure
0 In a 90-day dietary study by Paynter et al. (1960), male and female
rats were exposed to sodium dalapon (65% pure) at levels of 0, 11.5,
34.6, 115, 346 or 1,150 mg/kg/day. Increases in kidney and liver
weight were observed in both sexes at 346 and 1,150 mg/kg/day. The
No-Observed-Adverse-Effect-Level (NOAEL) in this study was identified
as 11.5 mg/kg/day base! on increases in kidney weight at higher
doses. (See discussion under Longer-term Health Advisory below.)
0 In a 1-year study, sodium dalapon (65% pure) was administered to
dogs by capsule at level's of 0, 15, 50 or 100 mg/kg/day. Based on
increases in kidney weight at 100 mg/kg/day, the NOAEL was identified
as 50 mg/kg/day (Paynter et a.'., 1960).
0 With the exception of an increase in kidney weight in male rats,
sodium dalapon (65% pure) was without effrt,-;t in a 2-year dietary study
(Paynter et al., 1960); the NOAEL in this study was 15 mg/kg/day.
(See discussion under Longer-tern Health Advisory below.)
Reproductive Effects
0 Administered in the diet, sodium dalapon (65% pure) had no effects on
reproduction in the rat at dose levels of approximately 30, 100 or
300 mg/kg/day (Paynter et al., 1960).
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Dalapon August, 1987
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Developmental Effects
0 Sodium dalapon (purity not specified) was not teratogenic in the rat
at doses as high as 2,000 mg/kg/day (Emerson et al., 1971; Thompson
et al., 1971). (See Ten-day Health Advisory below.)
Mutagenicity
0 Dalapon was not mutagenic in a variety of organisms including Salmonella
typhimurium, Escherichia coli, T4 bacteriophage, Streptomyces coelicolor
and Aspergillus nidulans (U.S. EPA, 1984). Although Kurinnyi et al.
(1982) reported that dalapon increased chromosome aberrations in mice,
the inadequate technical detail presented precluded an evaluation of
this study.
Carcinogenicity
0 No evidence of a carcinogenic response was observed in a 2-year
chronic feeding study in which sodium dalapon (65% pure) was
administered to rats at levels as high as 50 mg/kg/day for a period
of 2 years (Paynter et al., 1960).
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) = /L ( /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 of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
No data were found in the available literature that were suitable for
determination of the One-day HA value for dalapon. It is, therefore,
recommended that the Ten-day HA value for a 10-kg child (4.3 mg/L, calculated
below) be used at this time as. a conservative estimate of the One-day HA value.
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Dalapon August, 1987
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Ten-day Health Advisory
The rat teratology study by Emerson et al. (1971) has been selected to
serve as the basis for determination of the Ten-day HA for a 1 0-kg child.
In this study, sodium dalapon (purity not specified; assumed to be 100%) was
orally administered to pregnant rats over a 10-day period (days 6 through
15 of gestation) at doses of 0, 500, 1,000 or 1,500 mg/kg/day. Although no
compound-related teratogenic response was seen, there was a decreased in
weight gain in the dams at the lowest level tested, 500 mg/kg/day. Decreased
weight gain was also observed in the pups, but only at higher levels (1,000
and 1,500 mg/kg/day). Standards for dalapon are commonly expressed in terms
of the acid rather than the salt. Thus, it is necessary to convert the LOAEL
for the sodium salt, 500 mg/kg/day, to the equivalent value for the acid.
The LOAEL for dalapon as acid = (500 mg/kg/day) (143) = 430 mg/kg/day
1 65
where:
500 mg/kg/day = LOAEL for sodium dalapon.
143 = molecular weight of dalapon as acid in g/MWt.
1 65 = molecular weight sodium dalapon in g/MWt.
The Ten-day HA for a 10-kg child is calculated as follows:
Ten-day HA = (430 mg/kg/day) (10 kg) z 4.3 /: (4 300 /L)
(1,000) (1 L/day)
where:
430 mg/kg/day = LOAEL for dalapon as acid based on body weight
decreases in dams.
10 kg = assumed body weight of a child.
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a LOAEL from an animal study.
1 L/day = assumed daily water consumption of a child.
Longer-term Health Advisory
The results of Paynter et al. (1960) suggest that the subchronic and
chronic toxicity of dalapon are much the same. Specifically, in a 97-day rat
subchronic dietary study, sodium dalapon (65% sodium dalapon; 16% sodium salts
of related chloropropionic acids; 2% sodium pyruvate; 5% sodium chloride; 5%
water; 7% undetermined) produced an increase in kidney weight in female rats
at 34.6 mg/kg/day and higher exposure levels but not at 11.5 mg/kg/day (NOAEL).
Similarly, in a two-year rat chronic dietary study, sodium dalapon exposure
(65% pure) resulted in an increase in male kidney weight at 50 mg/kg/day but
not at 15 mg/kg/day (NOAEL). Considering both Paynter et al. (1960) rat
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Dalapon August, 1987
I
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dietary studies together, the 15 mg/kg/day NOAEL for sodium dalapon is
appropriate to calculate both a Longer-term HA and a Lifetime HA.
It is customary to express dalapon standards in terms of the acid rather
than the salt. The NOAEL used to derive the Longer-term HA is based on
studies (Paynter et al., 1960) in which rats were exposed to sodium dalapon
that was 65% pure. Thus, a NOAEL for dalapon as the pure acid must be
calculated:
The NOAEL for dalapon as pure acid = (15 mg/kg/day) (0.65) (143) , g mg/kg/day
165
where:
15 mg/kg/day « NOAEL for 65% pure sodium dalapon.
0.65 » purity of sodium dalapon used in determining NOAEL.
143 = molecular weight of dalapon as acid.
165 - molecular weight of sodium dalapon.
The Longer-term HA for a 1 0-kg child is calculated as follows:
Longer-term HA = (8 mg/kg/day ) (10 kg) = 0.8 mg/L (800 Ug/L )
(100) (1 L/day)
where:
8 mg/kg/day = NOAEL based on kidney weight increases in male rats.
1 0 kg = assumed body weight of a child.
1 00 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from animal study.
1 L/day = assumed daily water consumption of a child.
The Longer-term HA for a 70-kg adult is calculated as follows:
Lor jer-term HA = (8 "»g/*g/day) (70 kg) , 2.8 mg/L (2,800 ug/L)
(100) (2 L/day)
where all factors are the same except:
70 kg = assumed body weight of an adult.
2 L/day = assumed daily water consumption of an adult.
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Dalapon August, 1987
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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
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, 1986a), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.
The data used to determine the Lifetime HA are identical to those used
to determine the Longer-term HA. Using the NOAEL of 8 mg/kg/day from the
2-year rat study by Paynter et al. (1960), the Lifetime HA for the 70-kg
adult is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (8 mg/kgydav) = 08 /L (2>800 /L,
(2 L/day)
where:
0.08 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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Dalapon August, 1987
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Step 3: Determination of the Lifetime Health Advisory
Lifetime HA » (2.8 mg/L) (20%) - 0.56 mg/L (560 ug/L)
where:
2.8 mg/L = DWEL.
20% = assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
8 No evidence of carcinogenicity was found in a 2-year dietary study in
which sodium dalapon was administered to rats at levels as high as
50 mg/kg/day (Paynter et al., 1960).
8 Applying the criteria described in EPA's guidelines for assessment
of carcinogenic risk (U.S. EPA, 1986a), dalapon may be classified
in Group D: not classified. This group is for substances with
inadequate human and animal evidence of carcinogenicity.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
The American Conference of Governmental Industrial Hygienists suggests ^^
a Threshold Limit Value (TLV) of 1 ppm (6 mg/m3) as a time-weighted ^r
average for an 8-hour work day.
8 Tolerances have been established for dalapon in a wide variety of
agricultural commodities (CFR, 1985) ranging from 0.1 ppm in milk to
75 ppm in flaxseed.
VII. ANALYTICAL METHODS
0 Analysis of dalapon is by a gas chromatographic (GC) method applicable
to the determination of certain chlorinated acid pesticides in water
samples (U.S. EPA, 1986b). In this method, approximately 1 liter of
sample is acidified. The compounds are extracted with ethyl ether
using a separatory funnel. The derivatives are hydrolyzed with
potassium hydroxide, and extraneous organic material is removed by 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 not been determined
for this compound.
VIII. TREATMENT TECHNOLOGIES
0 No information on treatment technologies capable of effectively
removing dalapon from contaminated water was found in the available
literature.
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Dalapon August, 1987
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IX. REFERENCES
Brust, H. 1953. Hydrolysis of dalapon sodium salt solutions. E.G. Britton
Research Laboratory, The Dow Chemical Co., Midland, MI. November 4,
1953. Cited in Kenaga, 1974.
CFR. 1985. Code of Federal Regulations. 40 CFR 180.150.
Emerson, J.L., D.J. Thompson and C.G. Gerbig. 1971. Results of teratological
studies in rats treated orally with 2,2-dichloropropionic acid (dalapon)
during organogenesis. Report HH-417, Human Health Research and Develop-
ment Laboratories, The Dow Chemical Co., Zionsville, IN (cited in
Kenaga, 1974).
Helling, C.S. 1971. Pesticide mobility in soils, I, II, III. Proc. Soil
Sci. Soc. Amer. 35:732-748.
Hoerger, F. 1969. The metabolism of dalapon. Blood absorption and urinary
excretion patterns in dogs and human subjects. Unpublished report.
Dow Chemical Company (cited in Kenaga, 1974).
Holston, J.T., and W.E. Loomis. 1956. Leaching and decomposition of
2,2-dichloropropionic acid in several Iowa soils. Weeds. 4:205-217.
Kearney, P.C., et al. 1965. Behavior and fate of chlorinated aliphatic
acids in soils. Adv. Pest. Control Res. 6:1-30.
Kenaga, E.E. 1974. Toxicological and residue data useful in the environ-
mental safety evaluation of dalapon. Residue Rev. 53:109-151.
Kurinnyi, A.I., M.A. Pilinskaya, I.V. German and T.S. L'vova. 1982. Imple-
mentation of a program of cytogenic study of pesticides: Preliminary
evaluation of cytogenic activity and potential mutagenic hazard of 24
pesticides. Tsitologiya i Genetika. 16:45-49.
Meister, R., ed. 1984. Farm chemicals handbook. Willoughby, OH: Meister
Publishing Co.
Paynter, O.E., T.W. Tusing, D.D.' McCollister and V.K. Rowe. 1960. Toxicology
of dalapon sodium (2,2—dichloropropionic acid, sodium salt). Agr. Food
Chem. 8:47-51.
Redemann, C.T., and J.W. Hanaker. 1959. The lactic secretion of metabolic
products of ingested sodium 2,2-dichloropropionate by the dairy cow.
Agricultural Research, the Dow Chemical Company. Seal Beach, CA (cited
in Kenaga, 1974).
Smith, G.N., M.E. Getzendaner and A.H. Kutschinski. 1957. Determination of
2,2-dichloropropionic acid (dalapon) in sugar cane. J. Agr. Food Chem.
5:675. Cited in Kenaga, 1974.
Smith, G.N., Y.S. Taylor and B.S. Watson. 1972. Ecological studies on dalapon
(2,2-dichloropropionic acid). Unpublished report NBE-16. Chemical
Biology Res., The Dow Chemical Co., Midland, MI (cited in Kenaga, 1974).
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Dalapon August, 1987
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STORET. 1987.
Thiegs, B.J. 1955. The stability of dalapon in soils. Down to Earth, Fall
issue. Cited in Kenaga, 1974.
Thompson, D.J., C.G. Gerbig and J.L. Emerson. 1971. Results of tolerance
study of 2,2-dichloropropionic acid (dalapon) in pregnant rats.
Unpublished report HH-393. Human Research and Development Center, Dow
Chemical Company (cited in Kenaga, 1974).
Tracey, W.J., and R.R. Bellinger, Jr. 1958. Hydrolysis of sodium 2,2-dichloro-
ropionate in water solution. Midland Division, The Dow Chemical Co.,
Midland, MI (cited in Kenaga, 1974).
U.S. EPA. 1984. U.S. Environmental Protection Agency. Draft health and
environmental effects profile for dalapon. Environmental Criteria and
Assessment Office, Cincinnati, OH.
U.S. EPA. 1986a. U.S. Environmental Protection Agency. Guidelines for
carcinogen risk assessment. Fed. Reg. 51(185)s33992-34003. September 24.
U.S. EPA. 1986b. U.S. Environmental Protection Agency. U.S. EPA Method #3 -
Determination of chlorinated acids in ground water by GC/ECD, January
1986 draft. Available from U.S. EPA's Environmental Monitoring and
Support Laboratory, Cincinnati, OH.
Warren, G.F. 1954. Rate of leaching and breakdown of several herbicides
in different soils. NC Weed Control Conf. Proc., 11th Ann. Meeting,
Fargo, ND {cited in Kenaga, 1974).
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