March 31, 1987
EPICHLOROHYDRIN
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 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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This Health Advisory (HA) is based on information presented in the Office
of Drinking Water's Health Effects Criteria Document (CD) for Epichlorohydrin
(U.S. EPA, 1985a). The HA and CD formats are similar for easy reference.
Individuals desiring further information on the toxicological data base or
rationale for risk characterization should consult the CD. The CD is available
for review at each EPA Regional Office of Drinking Water counterpart (e.g.»
Water Supply Branch or Drinking Water Branch), or for a fee from the National
Technical Information Service, U.S. Department of Commerce, 5235 Tort Royal
Rd., Springfield, VA 22161, PB #86-118023/AS. The toll-free number is (800)
336-4700; in the Washington, D.C. area: (703) 487-4650.
II. GENERAL INFORMATION AND PROPERTIES
CAS No. 106-89-8
Structural Formula
H2C-CH-CH2C1
Synonyms
0 1-Chloro-2,3-epoxypropane, 3-chloro1-1,2-epoxypropane, (chloromethyl)
oxirane, 2-(chloromethyl) oxirane and chloropropylene oxide.
Uses
0 Used in the manufacture of: epoxide resins, surface active agents,
Pharmaceuticals, and agricultural chemicals (Verschueren, 1983).
Properties (U.S. EPA, 1985a)
Molecular Formula C3H5C1O
Molecular Weight 92.53
Physical State Colorless liquid
Boiling Point 116.1°C
Melting Point -57.2°C
Density
Vapor Pressure 12 mm at 20°C
Specific Gravity 1.18 at 20°C
Water Solubility 66 g/L at 20°C
Log Octanol/Water Partition 0.26
Coefficient
Taste Threshold ~
Odor Threshold 0.5 - 1.0 mg/L; 3 mg/L (Amoore and
Hautala, 1983)
Conversion Factor 1 mg/m3 = 0.265 ppm
1 ppm =3.78 mg/m3
Irritation Threshold 0.1 mg/L
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Occurrence
0 Total epichlorohydrin production in 1982 was approximately 350 mil-
lion pounds. Though epichlorohydrin reportedly hydrolyzes readily in
aqueous solution (hydrolysis half-life of 8.2 days at 20°C and pH 7)
to water soluble alcohols, its use in water treatment resins and
coatings make exposure possible (Mabey and Mill, 1978).
0 No information has been located in either State or Federal surveys to
indicate the presence or absence of epichlorohydrin in drinking water.
III. PHARMACOKINETICS
Absorption
0 Epichlorohydrin is absorbed readily following either oral, inhalation
or dermal exposures (U.S. EPA, 1985a).
0 Gingell at al. (1985) assessed the pharmacokinetics and metabolism
of epichlorohydrin in male Fischer 344 rats treated (6 mg/kg once by
gavage) with [2-14C] epichlorohydrin (98% pure) in water and sacrificed
after 3 days. Ready absorption was shown by an initial elimination
half-life of 2 hours and total excreta recovery of 91.61% of the
radiolabel.
0 Smith et al. (1979) have reported the extensive absorption of epichloro-
hydrin in water by male Fischer 344 rats (190 to 220 g) following a
single gavage exposure. Based on excretion data, the extent of
absorption, approximately 100% within 72 hours after administration,
,. ——appeared to be similar following doses of either 1 or iOO mgAg bw.
Smith et al. (1979) indicated that epichlorohydrin was absorbed
readily by male Fischer 344 rats (190 to 220 g) following a 6-hour
exposure to atmospheres containing 1 or 100 ppm epichlorohydrin
(approximately 3.78 or 378 mg/m3). Uptake rates of 15.48 and 1394
ug/hr were calculated for exposures to 1 and 100 ppm, respectively.
The investigators stated that these exposures correspond to doses of
0.37 and 33 mg/kg bw«
The toxicity study of Kremneva and Tolgskaya (1961 ) indicates that
epichlorohydrin also is absorbed following dermal exposure. When the
tails of mice were immersed in epichlorohydrin either for a single
exposure of 1 hour or for repeated exposures of 20 to 30 minutes/day
on 2 to 3 successive days, toxic signs and death were observed within
3 days.
Distribution
In the study by Gingell et al. (1985), 8-9% of 14C was in tissues,
with the highest levels (specific activity, dpm x 10~3/
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0 Smith et al. (1979) compared the distribution of [1,3-14C]-epichloro-
hydrin in male Fischer 344 rats following oral (100 mgAg bw) or
-inhalation (100 ppm for 6 hours) exposure. At 3 hours post-exposure
in the oral study and at the termination of inhalation exposure, the
plasma levels of radioactivity were 36.1 and 18.3 mg/g, respectively.
Concentrations in tissues were expressed as ug equivalents of epi-
chlorohydrin per g of tissue. After oral treatment, the greatest
concentrations were in stocach, followed by intestine, kidney, liver,
pancreas and lung. Following inhalation exposure, the highest
levels were in nasal turbinates, followed by intestine, liver and
kidney.
Metabolism
0 Gingell et al. (1985) concluded that the initial elimination half-
life of 2 hours indicated rapid metabolism in their study. Main
urinary metabolites were N-acetyl-S-(3-chloro-2-hydroxypropyl)-L-
cysteine and X -chlorohydrin, representing 36 and 4% of the delivered
dose, respectively. One major metabolite and 4 minor metabolites
were identified in urine. These investigators stated that the presence
of the two dominant urinary metabolites is.consistent with initial
metabolic reactions being conjugation of the epoxide with glutathione
and hydration of the epoxide.
0 Smith et al. (1979) administered [1,3-14c]-epichlorohydrin to male
Fischer 344 rats as single oral doses of 1 or 100 mg/kg bw or as
6-hour inhalation exposures to 1 or 100 ppm (approximately 3.78 or
378 mg/m-3). Urinary metabolites were separated by ion-exclusion
chromatography. Seven radioactive peaks were found in the urine
following oral dosing and six radioactive peaks following inhalation
exposure, but none corresponded to epichlorohydrin. The authors
noted that the patterns of urinary metabolite excretion were similar
following oral or inhalational dosing; metabolites were not identified.
0 Epichlorohydrin has two electrophilic centers and may bind to cellular
nucleophiles. It is also a substrate for epoxide hydratase resulting
in the formation of *-chlorohydrin which may be oxidized to oxalic
acid, converted to glycidol or phosphorylated to 3-chloroglycero-
phosphate (U.S. EPA, 1985a). However, Gingell et al. (1985) did not
find oxalic acid as a metabolite in their study.
0 Rossi et al. (1983) found that epichlorohydrin rapidly disappeared
from the blood of CD1 mice, with a half-life of approximately five
minutes, with f< -chlorohydrin appearing as epichlorohydrin levels
dropped. 2/ 50% was
excreted as urinary metabolites, and 39% was eliminated in feces.
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Smith et al. (1979) administered [1,3-14c]-epichlorohydrin by
single gavage doses of 1 or 100 mgAg to groups of four male Fischer
344 rats. In parallel experiments, four rats were exposed (head
only) to atmospheres containing 100 ppm (378 mg/m^) epichlorohydrin
for six hours. An additional three rats were exposed to atmospheres
containing 1 ppm (3.78 rag/m^) for six hours. The rates or routes of
excretion essentially were unaffected by either the route of exposure
or the dose administered. Urine was the major route of excretion,
accounting for 46% to 54% of the dose. An additional 25% to 42% was
recovered as -4C02 in the expired air. Only 3% to 6% of the dose was
recovered in the feces. Excretion was biphasic, with an initial
rapid phase that dominated the first 24 hours post-exposure and a
slower second phase that was dominant after 24 hours. The calculated
half-lives for elimination from the plasma were 1 to 2 hours and 26
to 27 hours for the fast and slow phases, respectively.
IV. HEALTH EFFECTS
Humans
0 In humans, acute effects have been reported following both dermal and
inhalation exposures (U.S. EPA, 1985a). Dermal exposure produces
predominantly local irritation effects, but inhalation produces
significant systemic effects, including hepatic and renal toxicity.
In one case report of a worker exposed to epichlorohydrin vapor,
systemic effects were evident .for at, least 2 years after the exposure.
(U.S. EPA, 1985a) Chronic exposure to epichlorohydrin has been
associated with chromosome and chromatid breaks, decreased hemoglobin
concentration, decreased erythrocyte counts and decreased leukocyte
counts. Increases (not statistically significant) in the mortality
due to lung cancer have been reported in workers sequentially exposed
to isopropyl alcohol and epichlorohydrin (U.S. EPA, 1985a). No
effects on reproductive function have been detected.
Animals
Short-term Exposure
Epichlorohydrin is acutely toxic following oral, percutaneous, subcu-
taneous or respiratory exposure, producing similar symptoms in each
case. At the site of application, epichlorohydrin is a strong
irritant. The major acute systemic effects occur in the central
nervous system, with death being due to depression of the respiratory
center. The major internal organs affected are the lungs, liver and
kidneys (U.S. EPA, 1985a).
Oral doses as low as 10 mgAg for 5 days/week for 2 weeks resulted
in decreased (p <0.05) erythrocyte counts in male rats and decreased
(p <0.01) kidney/body weight ratios in females (Van Esch, 1981).
Similar exposures to 40 or 80 mgAg resulted in degenerative changes
in the kidneys of both male and female rats.
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Epichlorohydrin March 31, 1987
Long-term Exposure
0 Epichlorohydrin given in drinking water at levels of 375, 750 and
1,500 ppm (18, 39 and 89 nig/kg/day) to male Wistar rats for 81 weeks
induced forestomach hyperplasia and decreased body weights at all
doses (Konishi et al., 1980).
0 with gavage administration of epichlorohydrin in water at doses of 2
and 10 mgAg* 5 days /week for 104 weeks, stomach hyperplasia and a
dose-related decrease in white blood cells were observed in male and
female Wistar rats (Van Esch, 1982).
0 Inhalation exposure of Fischer 344 rats, Sprague-Dawley rats,
B6C3P1 mice and New Zealand rabbits to epichlorohydrin at 19 mg/m3
for 90 days was without observable effect. Higher exposure levels
induced nasal irritation, eye irritation, kidney lesions and respiratory
tract lesions (Quast et al., 1979; John et al., 1983).
0 Lifetime inhalation exposure of male Sprague-Dawley rats to 38 and
114 mg/m3 epichlorohydrin elicited kidney lesions (Laskin et al., 1980).
Reproductive Effects
0 Male and female Wistar rats were given epichlorohydrin in water start-
ing 10 days before mating and continuing for three months (Van Esch,
1981). A dose of 2 mgAg was ineffective. A 10 mgAg dose reduced
. fertility and crossmating with untreated rats attributed the antifer-
tility effect to males. Sterility of male rats given epichlorohydrin
orally also was observed by Hahn (1970) and Cooper et al. (1974)
with gavage doses of '15 mgAg and higher for 15 and 5 days, respectively?
however, these investigators showed the effect to be reversible.
0 Exposure of male rats to epichlorohydrin by inhalation at levels above
19 mg/m3 for 10 weeks resulted in reversible sterility, and the
fertility of male rabbits was unaffected by inhalation exposure
levels of epichlorohydrin as high as 189 mg/m3 (John et al., 1983).
Developmental Effects
0 Epichlorohydrin was not teratogenic when given by gavage in cotton-
seed oil to pregnant CD rats and CD-1 mice on days 6 through 1 5' of
gestation (Marks et al., 1982). Doses above 40 mgAg were maternally
toxic (reduced body weight, increased liver weight, death) in rats.
Doses above 80 mgAg were maternally toxic (increased liver weight,
death) and fe to toxic (reduced body weight) to mice.
Inhalation exposures of pregnant Sprague-Dawley rats and New Zealand
rabbits to 9.5 and 95 mg/m3 of epichlorohydrin during gestation days
6 through 15 (rats) and 6 through 18 (rabbits) were neither teratogenic
nor fetotoxic. Pregnant rats exposed to 95 mg/m3 weighed less than
controls (Pilny et al., 1979).
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Mutagenicity
0 Epichlorohydrin is a rautagen in several systems (U.S. EPA, 1985a).
It is a potent inducer of base-pair substitution-type mutations in
prokaryotic systems. Incubation with mammalian liver homogenates
results in a marked reduction in mutation frequency. Epichlorohydrin
also induces gene mutations and very likely chromosomal aberrations
in mouse lymphoma cell cultures (Moore-Brown and Clive, 1979) and
clastogenesis in human lymphocytes in vitro (Norppa et al., 1981)
but not in rat liver cell cultures (Dean and Hodson-Walker, 1979).
Epichlorohydrin was found to induce sister chromatid exchange in
cultured human lymphocytes (Norppa et al., 1981; Carbone et al.,
1981; White, 1980). Examination of occupationally exposed workers
indicates that chromosomal aberrations also occur in vivo (Picciano,
1979a,b; Kucerova et al., 1977; Sram et al., 1976).
0 In in vivo studies, epichlorohydrin treatment results in an increased
incidence of sex-linked recessive lethals in Drosophila when admini-
stered by injection, but not when incorporated in the food (Knapp
et al., 1982; Wurgler and Graf, 1981). In other in vivo studies,
epichlorohydrin has produced negative results in the mouse dominant
lethal assay (Epstein et al., 1972; Sram et al., 1976) and the mouse
micronucleus assay (Kirkhart, 1981; Tsuchimoto and Matter, 1981).
Clastogenic effects of epichlorohydrin in bone marrow cells in vivo
were found in mice (Sram et al., 1976) but not in rats (Dabney
et al., 1979).
Carcinogenicity
0 Epichlorohydrin is carcinogenic at the site of administration.
0 Administration of 375, 750 and 1,500 ppm epichlorohydrin in drinking
water [equivalent to 18, 39 and 89 mg/kg/day based on data by the
authors (total doses of 5.0, 8.9 and 15.1 g/rat during 81 weeks of
treatment divided by body weight)] to male Wistar rats for 81 weeks
resulted in forestomach hyperplasia at all doses and papillomas and
carcinomas of the forestomach at the two highest doses (Kbnishi
et al., 1981).
0 Lifetime gavage treatment of male and female Wistar rats with aqueous
epichlorohydrin solution at doses of 2 and 10 mg/kg induced papillomas
and carcinomas of the forestomach (Wester et al., 1985; Van Esch,
1982).
0 Laskin et al. (1980) found nasal carcinomas in male Sprague-Dawley
rats exposed to 378 mg/m^ of epichlorohydrin by inhalation 6 hours/day,
5 days/week for six weeks followed by lifetime observation.
Subcutaneous injection of epichlorohydrin in ICR/Ha Swiss mice induced
local sarcomas; epichlorohydrin was effective as an initiator but not
as a complete carcinogen on the. skin of ICR/Ha Swiss mice (Van Duuren
et al., 1972; 1974).
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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) = m /L ( *}
(UF) x ( L/day)
where:
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in rag/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).
Organoleptic Properties
A reported threshold for odor perception of epichlorohydrin is 0.5 to
1.0 mg/L, and 0.1 mg/L was cited as the threshold for its irritant action by
the MAS (1980). Amoore and Hautala (1983) reported an odor threshold of 3
mg/L.
One-day Health Advisory
Because appropriate data for calculation of a One-day HA are not avail-
able, the Ten-day HA (0.14 mg/L) is recommended for use as the One-day HA.
Ten-day Health Advisory
The reproductive toxicity study by Van Esch (1981) can be used to derive
the Ten-day HA. In this study, male and female rats were given epichloro-
hydrin by gavage 5 days/week at doses of 0, 2 or 10 mg/kg- Exposure was
started 10 days prior to mating and continued until the Fjjrj generation was
produced. The fertility index at the first mating was reduced in the high-
dose group but not in the low-dose group. The study of Hahn (1970) which
reported infertility in male rats exposed by gavage to epichlorohydrin at
15 mg/kg/day for 12 days supports an assumption that at least a portion of
the reduced fertility index observed by Van Esch (1981) was the result of
infertility in the males associated with the ten-day exposure prior to mating.
In this study, 2 mg/kg was a NOAEL for reproductive effects and is appropriate
for use in deriving the Ten-day HA.
Using the NOAEL of 2 mgAg/day, the Ten-day HA for a 10-kg child is
calculated as follows:
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Ten-day HA = 2 mg/kg/day) (10 kg) (5) = 0>14 mg/L (140 ug/L)
y (1005 (1 L/day)fTT
where:
2 mg/kg/day = NOAEL based on absence of reproductive toxicity in rats.
10 kg = assumed body weight of a child.
5/7 = conversion of dose to represent continuous exposure
(7 days per week).
1 L/day = assumed daily water consumption of a child.
Although the antifertility effect in male rats in the Van Esch (1981)
study relates to men as a specific sensitive subpqpulation for this effect,
this study is preferred for the calculation of a Ten-day HA for the general
population because of its design with oral short-term exposure and its
demonstration of no-effect and effect levels. Additionally, the 2 mgAg
NOEL in the Van Esch (1981) study appears consistent with the dose responses
in the overall Van Esch (1981) work where both systemic and reproductive .
effects were found with 10-day oral exposures to 10 rag/kg of epichlorohydrin.
Longer-term Health Advisory
There are insufficient data for calculation of a Longer-term HA. The
DWEL (0.07 mg/L), is recommended as a conservative estimate of the Longer-term
HA.
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 NQAEL (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.
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Epichlorohydrin
March 31, 1987
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Of the reviewed studies in which the effects of long-term exposure to
epichlorohydrin were investigated (Laskin et al., 1980; Konishi et al., 1980,
also reported by Kawabata, 1981; Wester et al., 1985, also reported by Van Esch,
1982), the Laskin et al. (1980) study was selected as the most appropriate
from which to derive the DWEL. Forestomach hyperplasia in all three treatment
groups and papillomas and carcinomas of the forestomach in the two highest
dose groups were found in the study by Konishi et al. (1980). Since the
hyperplasia could be considered a pre-neoplastic effect and the progression
of forestomach lesions beyond the 81-week duration of this btudy is uncertain,
it would be questionable to use this effect in the low-dose group (18 mg/kg/day)
for calculating a DWEL for drinking water exposure. Dose-response for
toxicity/carcinogenicity in the Konishi et al. (1980) drinking water study
is given preference over that in the bolus gavage dosing study by Wester, et
al. (1985), and use of the estimated 2.16 mg/kg/day dose in the Laskin, et
al. (1980) study is concluded to be consistent with the dose-response indicated
by the Konishi et al. (1980) study. The LOAEL based on renal damage of 2.16
mg/kg/day estimated from the data in the Laskin et al. (1980) study was,
therefore, used to derive a DWEL. Additionally, carcinogenic effects were
not apparent at the LOAEL in the Laskin et al. (1980) study. Using this
LOAEL, the DWEL is derived as follows:
Step 1: Conversion of Inhalation Exposure to Oral Exposure
Applying the 38 mg/m3 inhalation LOAEL in the Laskin et al. (1980)
study and the assumptions in U.S. EPA (1985a) for converting inhalation
exposure to oral exposure for the rat, the estimated oral dose would be:
(38 mg/m3)(0.0093 m3/hr)(6 hr/day) (5)(0.5)
(0.35 kg) (7)
2.16 mg/kg/day
where:
38 mg/m3 = LOAEL based on kidney toxicity in rats.
0.0093 m3 = amount of air breathed by a rat/hour.
6 hr/day = a 6-hour exposure each day.
5/7 = adjust from a 5 days/week exposure to 7 days/week,
0.5 = the assumed inhalation absorption factor.
0.35 kg = the assumed weight of a rat.
Step 2: Determination of the Reference Dose (RfD)
RfD = (2.16 mg/kg/day) = Q.002 mg/kg/day (2 ug/kg/day)
where:
2.16 mg/kg/day = LOAEL based on kidney toxicity in rats.
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a LOAEL from an animal study.
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Step 3: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0«002 mg/kg/day) (70 kg) = 0>07 /L (70
(2 L/day)
0.002 mg/kg/day = RfD.
70 kg = assumed body weight of an adult.
2 L/day = assumed daily water consumption of an adult.
Epichlorohydrin may be classified in Group B: Probable human carcinogen.
The estimated excess cancer risk associated with lifetime exposure to drinking
water containing epichlorohydrin at 70 ug/L is approximately 2 x 10-5. This
estimate represents the upper 95% confidence limit from extrapolations prepared
by EPA's Carcinogen Assessment Group using the linearized/ multistage model.
The actual risk is unlikely to exceed this value, but there is considerable
uncertainty as to the accuracy of risks calculated by this methodology.
Evaluation of Carcinogenic Potential
0 Applying the criteria described in EPA's guidelines for assessment of
carcinogenic risk (U.S. EPA, 1986), epichlorohydrin may be classified
in Group B2: Probable human carcinogen. This category is for agents
for which there is inadequate evidence from human studies and
sufficient evidence from animal studies.
0 The study of Konishi et al. (1980) -provides appropriate data for a
quantitative risk assessment based on the relevant route of exposure
and the observed dose-response pattern. Using the calculated q-|* of
9.9 x 10-3 (mg/kg/day ) -1 , the 95% upper-limit lifetime dose associated
with a 10-5 risk level may be calculated to equal 70.7 ug/day.
Assuming an average water consumption of 2 L/day, this risk level
corresponds to a water concentration of 35.4 ug/L. Corresponding
levels for 10-6 and 10-4 are 3.54 and 354 ug/L, respectively.
0 Maximum likelihood estimates as well as 95% upper limits of cancer
risks by the multistage model have been calculated (U.S. EPA, 1984).
For example, at 1 0 ug/L cancer risk estimates are 1 .4 x 10-17 (MLE)
and 2.8 x 10-6 (UL)»and at 100 ug/L cancer risk estimates are 2.6 x
10-14 (MLE) and 2.8 x 10-5 (UL) .
0 The EPA's Carcinogen Assessment Group has estimated cancer risks with
other models besides the multistage (U.S. EPA, 1984). As an example,
10 ug/L lifetime exposure was associated with additional risks (95%
upper confidence limit) of 2.8 x 10-5 by the multistage, 3.4 x 10-5
by the one-hit, 0 by the Weibull, and 0 by the log-probit. While
recognized as statistically alternative approaches, the range of
risks described by using any of these modeling approaches has little
biological significance unless data can be used to support the selec-
tion of one model over another. In the interest of consistency of
approach and in providing an upper bound on the potential cancer risk,
the EPA has recommended use of the linearized multistage approach.
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Epichlorohydrin March 31, 1987
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0 Epichlorohydrin is classified as a 2B carcinogen by IARC (1982) with
sufficient animal evidence and inadequate human evidence.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 The NAS (1980) SNARLs (Suggested-Nq-Adverse-Response-Levels) for
1- or 7-day exposures to apichlorohydrin are 0.84 and 0.53 mg/L,
respectively. An ADI (Acceptable Daily Intake) or a cancer risk was
not calculated by the NAS (1980).
0 The ACGIH has recommended a TLV (Threshold Limit Value) of 2 ppm
(10 mg/m3) (ACGIH, 1982). Current OSHA standards allow a TWA occupa-
tional exposure of 19 mg/m3 (29 CFR 1910.1000); however, they are
currently considering lowering this value to 0.5 ppm (2 mg/m3) with
a ceiling value of 15 ppm (60 mg/m3) for 15 minutes. Occupational
standards in other countries range from 0.26 ppm in Russia and
Czechoslovakia to 3.6 ppm in the Federal Republic of Germany (Sram,
et al., 1980).
0 Epichlorohydrin has not been regulated under the Safe Drinking Water
Act; however, discharge of >1,000 pounds (454 kg) into navigable
waters is prohibited under the Clean Water Act (40 CFR 116).
0 Epichlorohydrin is also classified as a "hazardous waste" by the U.S.
EPA and quantities exceeding 100 kg must be disposed of in a special
landfill (40 CFR 261; 40 CFR 122).
0 The proposed RMCL by the U.S. EPA Office of Drinking Water is zero
(U.S. EPA, 1985b).
VII. ANALYTICAL METHODS
0 There is no standardized method for the determination of epichloro-
hydrin in drinking water samples. However, epichlorohydrin may be
determined by a purge-and-trap gas chromatographic/mass spectrometric
procedure used for the determination of volatile organic compounds
in water (U.S. EPA, 1985c). This method calls for the bubbling of
an inert gas through the sample and trapping epichlorohydrin on an
adsorbent material. The adsorbant material is heated to drive off
epichlorohydrin onto a gas chromatographic column. The gas chromato-
graph is temperature programmed to separate the method analytes which
are then detected by the mass spectrometer.
VIII. TREATMENT TECHNOLOGIES
0 No data are available on the removal of epichlorohydrin from potable
water by any treatment technique (ESE, 1984; U.S. EPA, 1985d).
0 The amenability of epichlorohydrin to removal by conventional treat-
ment or by adsorption is not known. The Henry's Law Constant for
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Epichlorohydrin
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March 31, 1987
eptchlorohydrin has been estimated to be 2.44 x 10~5 atm x m3/mole
(ESE, 1984). This value suggests that aeration is unlikely to be a
successful removal technique for epichlorohydrin.- It also has been
concluded that epichlorohydrin would not be removed from water by
ozone oxidation (U.S. EPA, 1985d).
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Epichlorohydrin March 31, 1987
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