August, 1968
1,3-OXCHLOROPROPBNK
Health Advisory
Office of Drinking Hater
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.
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. Bxcess cancer risk
estimates may also be calculated using the one-felt, Heibull, 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
assumption*, the estimates that are derived can differ by several orders of
magnitude*
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1,3-0ichloroprop«n« August, 1988
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ZX. GENERAL INFORMATION AND PROPERTIES
CAS No. 542-75-6
Structural Foraula
C1CH2 H aCH2 Cl
> / ^ /
c - c c - c
' * t \
H Cl H H
(trans) (eis)
1/3-Dichloropropene
(approximately 46% trans/42% cis)
Synonyms
Dichloro-1,3-propene; 1,3-dlchloro-1-propene; cis/trans-1,3-dichloro-
propene; 1,3-0; OCP; D-0 (approximately 28% cis/27% trans)
Uses
• OCP is the active ingredient in Telone*, a registered trademark of
the Dow Chemical Company.
• The pesticide 1, 3-dichloropropene (OCP) is a broad spectrum soil
fumigant to control plant pests. Its major use is for nematode
control on crops grown in sandy soils of the Eastern, Southern and
western U.S.
0 The usage of OCP has increased due to cancellation of the once widely
used product containing ethylene dibromide (BOB) and dibromochloro -
propane (DBCP) (U.S. EPA, 1986a).
• Estimated usage of OCP containing products in 1984 to 1985 ranged from
about 34 to 40 million pounds (U.S. EPA, 1986a).
Properties (Dow Chemical USA, 1977, 1982; Clayton and Clayton, 1981)
Chemical Formula
Molecular Height 110.98 (pure isomers)
Physical State (25«C) Pale yellow to yellow liquid
Boiling Point about 104-C (104.3*C, cis; 112*C, trans)
Density (25«C) 1.21 g/mt
Vapor Pressure (25*C) 27.3mm-Hg
Specific Gravity about 1.2 (20/20*C)
Water Solubility (25°C) 0.1 to about 0.25% (1 to 2.5 g/L)
reported; miscible with most organic
solvents
Log Octanol/Water Partition 25
Coefficient
Conversion Factor (25*C)(air) 1 mg/L » 220 ppm; 1 ppm -4.54 mg/n3
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1,3-Dlchloropropene August, 1988
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oeeurrence
• In California (Madefy et al., 1982), 54 wells ware examined in areas
where Telone or 0-0 were used for several years. The well water did
not have measurable aoouats of OCP «0.1 ppb).
• Monitoring data from New York have shown positive results for OCP in
ground water (U.S. EPA, 1986b).
• In deep well sampling in southern California (65 to 1/200 foot depths),
no DCP was detected. In shallow wells (3 to 4 meters) around potato
fields in Suffolk County/ NY, OCP was detected up to 138 days after
application (OPP, 1988).
• OCP has been found in 41 of 1/088 surface water staples analyzed and
in 10 of 3/949 ground water samples (STORBT, 1988). Samples were
collected in 800 surface water locations and 2/506 ground water
locations; OCP was found in 13 states. The range of concentrations
found In ground water was 0.2 ug/L to 90 ug/L. nie 85th percentlle
of all non-zero samples was 1.3 ug/L in surface water and 3.4 ug/L
in ground water* This information is provided to give a general
impression of the occurrence of this chemical in ground and surface
waters as reported in the STORET database. The individual data
points retrieved were used as they came from STORET and have not been
confirmed as to their validity. STORBT data is often not valid when
individual numbers are used out of the context of the entire sampling
regime/ as they are here. Therefore/ this information can only be
used to form an impression of the intensity and location of sampling
for a particular chemical.
Environmental Fate
• Available data indicate that DCP does leach to ground water. However,
the relative hydrolytic instability of the parent compound would
mitigate the potential for extensive contamination (U.S. EPA/ I986b;
U.S. EPA/ 1986c).
• The half-life of 1,3-OCP in soil was reported by Laskowski et al.
(1982) to be approximately 10 days while Van Oijk (1974) reported
3 to 37 days depending on soil conditions and analytical methods.
• OCP hydrolyses as a function of temperature not as a function of pH.
At 10«C, the half-life is 51 days while at 20*C it is 10 to 13 days.
Chloroallyl alcohol is the main hydrolytic degradate. Some phololysis
of OCP does occur (OPP/ 1988).
0 In laboratory aerobic soil metabolism studies/ OCP degrades to
chloroallyl alcohol in 20 to 30 days where soil pH is between 5.0 and
7.0, the temperature is between 15 and 20*C and the organic matter
content is from 1.5 to 11.6 percent in sandy loam or clay soils. In
anaerobic soil metabolism studies, OCP degrades to chloroallyl alcohol
to less than 8 percent in 30 days. For anaerobic aquatic metabolism
studies/ the half-life was reported to be about 20 days at pBs of
6.9 to 7.5 (OPP/ 1988).
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1,3-Oichloropropene Auguat, 1983
• In • field dissipation study done in the Netherlands, OCP (220-250 lb/T
injected into the soil at 9 to 19 on depths was found to move rapidly
downward over a 2 week period. In a similar study in Delano, CA, DCP
was injected at 1,310 1/ha to 1,638 1/ha (-Ib/A) to 81 em. Samples
at 14 days noted the presence of OCP (up to 0.5 ppm) at all depths to
8 feet (OPP, 1988).
III. PHARMACOKINETICS
Absorption
• Toxicity studies indicate that OCP is absorbed from skin, respiratory
and gastrointestinal systems (Clayton and Clayton, 1981).
• Oral administration of DCP in rats resulted in approximately 90%
absorption of the administered dose (Hutson et •!., 1971).
Distribution
• Radiolabeled 14C D-D (55% DCP) was administered orally in arachis
oil in rats. After 4 days, most of the administered dose, based on
measured radioactivity, was recovered primarily in orine and there
were insignificant amounts (less than 5%) remaining in the gut,
feces, skin and carcass (Rutson et al., 1971).
Metabolism
• cis-Dichlorqpropene in corn oil was given as a single oral dose
(20 mg/kg bw) to two female Wistar rats. Urine and feces were
collected separately. Die main urinary metabolite (92%) was N-*cetyl-
S-[(cis)-3-chloroprop-2-enylJ cysteine. The cis-DCP has also been
shown to react with glutathione in the presence of rat liver cystol
to produce S[(cis)-3-chloroprop-2-enyl]glutathione. The cis-DCP is
probably biotransformed to an intermediate glutathione conjugate and
then follows the mercapturic acid pathway and is excreted in the
urine as a cysteine derivitive (Climie and Morrison, 1978).
• Zn a study conducted by Dietz et al. (1984) rats and mice administered
(via gavage) up to 50 and 100 mg DCP/kg bw, respectively, demonstrated
no evidence of metabolic saturation.
Excretion
Zn two studies (Hutson et al., 1971} Climie and Morrison, 1978)
1*C cis- and/or trans-DCP, administered orally in rats, were excreted
primarily in the urine in 24 to 48 hours. When pulmonary excretion
was evaluated (Hutson et al., 1971), the cis and trans isomers were
3.9% and 23.6% of the administered dose, respectively. Most of the
cis-OCP was excreted in the urine.
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1,3-Oichloropropene August, 1988
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ZV. mm.TH
Humana
• The only known human fatality occurred a few hours after accidental
infection of D-D mixture. The dosage was unknown.' Symptoms were
abdominal pain, vomiting, muscle twitching and pulmonary edema.
Treatment by gastric lavage failed (Gosselin et al., 1976).
• Inhalation of DCP at high vapor concentrations resulted in gasping,
refusal to breathe, coughing, substernal pain and extreme respiratory
distress at vapor concentrations over 1,500 ppm (Gosselin et al.,
1976).
• Venable et al. (1980J studied 64 male workers exposed to three carbon
compounds including DCP to determine if fertility was adversely
affected. The exposed study population was divided into <5 years
exposure and >S years exposure. Sperm counts and percent normal
sperm forms were the major variables evaluated* Although the at'udy
participation rate for the exposed group was only 64%, no adverse
effects on fertility were observed.
Animals
Short-term Exposure
• DCP is moderately toxic via single-dose oral administration. A
technical product containing 92% cls-/trans-DCP was administered by
gavage as a 10% solution in corn oil to rats. The oral LDgQS in male
and female rats were 713 and 740 mg/Tcg, respectively (Torkelson and
Oyen, 1977). In another study, the oral LDso in the mouse for botn
males and females was 640 mg/kg (Toyoshlma et al., 1978).
Dermal/Ocular Effects
• The percutaneous LOsos for male and female mice dosed with DCP were
greater than 1,211 mg/kg (Toyoshima et al., 1978).
• The percutaneous administration of DCP in rabbits (3 g/kg) resulted
in mucous nasal discharge, depressed respiration and decreased body
movements. The 1.050 by this route was 2. 1 gAg (Torkelson and Oyen,
1 977) .
• Primary eye irritation and primary dermal irritation studies in
rabbits indicated that DCP causes severe conjunctival irritation,
moderate transient corneal injury and slight skin erythema/edema.
Bye irritation was reversible 8 days post-instillation. The dermal
LD50 in rabbits was 504 mg/kg (Dow, 1978).
Long-term Exposure
• Rats, guinea pigs, rabbits and dogs were exposed to 4.5 or 13.6
DCP in air for 7 hours per day, and 5 days per week for 6 months
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1,3-Oichloropropene Augupt, 1968
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The only effect noted was alight cloudy availing of ranal tubular
epithelium in mala rats axpoaad to tha high doaa (Torkalaon and Cyan,
1977).
Fiachar 344 rata and CD-I albino mice were exposed to Telone ZZ
(Production Grade) by inhalation expoaure, 6 hours per day for 13
weeks at concentrations of 11.98, 32.14, or 93.02 ppm. Gross pathology
revealed an Increased incidence of kidney discoloration in the treated
male rats relative to the control group. The significance of this
leaion is unknown (Coate et al., 1979).
Solutions of Telone (78.5% DCP) in propylene glycol were administered
by gavage to 10 rats/sex/doae for aix daya per week for a period of
13 weeks. The dose levels were 1, 3, 10 or 30 mg/kg/day. The control
groups were given propylene glycol. The daily administration of DCP
to rats by stomach intubation up to a dosage of 30 mg/kg/day did not
reault in any major adverae effects. No significant effects on body
weight, food consumption, hematology and histopathology were noted.
However, at the 10 and 30 mg/kg/day doses, the relative weight of the
kidney of males was higher than controla. The authors conclude that
the no-toxic-effect level for OCP was between 3 and 10 mgAg/day.
The actual Ho-Observed-Adverse-Effect-Level (NOAEL) was 3 mgAg/day
(Til et al, 1973). This is the only study that can be used to develop
a reference dose. However, because the design does not ideally
addresa drinking water, a modifying factor will be used.
The National Toxicology Program (NTP, 1985) evaluated the chronic
toxicity and carcinogenicity of Telone ZZ in rats and mice. These
studies utilized Telone ZZ fumigant containing approximately 89%
cis- and trans-OCP. Groups of 52 male and female F344/M rats (doses
0, 25 or 50 mg/kg) and 50 male and female B6C3F1 mice (doses 0, 50
or 100 mg/kg) were gavaged with Telone ZZ in corn oil, 3 days per
week up to 104 weeks. Ancillary studies were conducted in which
dose groups containing five male and female rats were killed after
receiving Telone ZZ for 9, 16, 21, 24 or 27 months. Toxic effects
(noncarcinogenic) included basal cell or epithelial hyperplasia of
the forestomach of rats and mice at all treatment levels of DCP.
Epithelial hyperplasia of the urinary bladder of mice occurred at
both treatment levels in males and females. Kidney hydronephrosis
also occurred in mice. The study in male mice waa considered
inadequate due to the deatha of vehicle control animals. Many
chronic toxicity parameters (hematology/ clinical chemistry) were not
determined. The DCP used in the NTP study h«d a different stabilizer
from the current Telone ZZ.
Scott et al. (1987) exposed groups of male and female B6C3F1 mice
(70 animals/sex/exposure concentration) to vapors of Telone ZZ* soil
fumigant for 6 hours/day, 5 days/week for up to 24 months at 0, 5,
20 or 60 ppm. Urinary bladder effects including hyperplasia of
bladder epithelium were noted in both sexes at 20 and 60 ppm. Hyper-
trophy and hyperplasia of the nasal respiratory mucosa were observed
in most 60 ppm exposed mice of both sexes and in 20 ppm exposed
females. Hyperplasia of the epithelial lining of the nonglandular
portion of the stomach was observed in 60 ppm exposed males.
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1,3-Oichloropropene August, 1968
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•t al. (1987) exposed group* of 70 male and female Fischer 344
rat* to vapors of Telone II* soil fumlgant for 6 hours/day, 5 days/week
for up to 24 months at targeted concentration* of 0, 5, 20 or 60 ppm.
the MOAIL was 20 ppm. The highest do*e caused hlstopathological
changes in nasal tissue as well as a decrease in body weight gain
during the first year of this study. Males and females exposed to*
60 ppa showed decreased thickness and erosions of the nasal epithelium
as well as minimal submucosa fibrosis.
Reproductive Effects
• Groups of male and female Histar rats were exposed to technical D-D
at 0, 64, 145 and 443 mg/m3 (0, 14, 12 or 94 ppa) for 5 days per week
over 10 weeks. Hale mating indices, fertility indices and reproductive
indices were not affected by D-D exposure. No gross morphological
changes were seen in sperm. Female mating, fertility and other
reproductive indices were normal. Litter sices and weights were
normal and pup survival over 4 days was not influenced by exposure
(Clark et al., 1980).
• Breslin et al. (1987) exposed by inhalation groups (F0) of 30 males
and 40 females for 10 weeks, 6 hours/day, 5 days/week to Telone II*
at concentrations of 0, 10, 30 and 90 ppm prior to breeding. Exposure
was increased to 7 days/week during breeding at weeks 11 to 13.
Exposure of PI male and female parents to Telone 12* began after
weaning (approximately week 32 of the study) and continued for
12 weeks (5 days/week and 6 hours/day), The NQAEL for reproductive
effects in the study was *90 ppa, the highest dose tested. Conception
indices of females were somewhat reduced in the Fj and ?2 generations.
At 90 ppm, both males and females developed hyperplasia of respiratory
epithelium and focal degeneration of olefactory tissue. Decreased
body weight was observed in males and females exposed to 90 ppm.
Developmental Effects
• Hanley et al. (1987) investigated the effects of inhalation exposure
to DCP on fetal development in rats. Pregnant Fischer 344 rats were
exposed to 0, 20, 60 and 120 ppm DCP for 6 hr/day during gestation
day* 6 to 15. Maternal body weight gain was depressed in all of the
DCP««xposed rats in a dose-related manner. Therefore, the Lowest-
Observed-Adver*e-Sffect Level (LOAEL) for this effect was 20 ppm DCP.
There was also significant depression of feed consumption in all
exposed rats, along with decreases in water"consumption in rats
exposed to 120 ppm DCP. At 120 ppm there were significant increases
in relative kidney weights and decreases in absolute liver weights in
all exposed rats. There was a statistical increase in the incidence
of delayed ossification of the vertebral centra of rats exposed to
120 ppm DCP. This effect is of little toxicological significance due
to maternal toxicity observed at 120 ppm DCP.
• Hanley et al. (1987) also studied the effects of Inhalation exposure
to DCP on fetal development in rabbits. Pregnant New Zealand White
rabbits were exposed to 0, 20, 60 or 120 ppm DCP for 6 hr/day during
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1,3-Dichloropropene August, 1988
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gestation days 6 through 18. In rabbits, evaluation of maternal
weight gain over the entire exposure period indicated significant
exposure-related decreases in both the 60- and 120-vpm groups.
Therefore, the KOAIL was 20 ppm OCP. Statistically significant
decreases in the incidence of delayed ossification of the hyoid and
presence of cervical spurs among the exposed group were considered
within normal variability in rabbits.
Mutaqenicity
• Tests of commercial formulations containing DCP (DeLorenzo et al.,
1975; Flessel, 1977; Neudecker et al., 1977; Brook* et al., 1978;
Sudo et al., 1978; Stolzenberg and Bine, 1980), a mixture of pure
cia-OCP and tran*-OCP (DeLorenzo et al., 1975), and pure cis-OCP
(Brook* et al, 1978) were poeitive in the Salmonella typhimurium
•train* TA1535 and TA100 with and without metabolic activation.
These result* indicate that DCP act* by base^alr substitution and
is a direct acting mutagen.
• OCP may be a mutagen that acts via frame shift mutation since studies
by DeLorenzo at al. (1975) reported poeitive result* in TA1978 (with
and without metabolic activation) for a commercial mixture of OCP and
a mixture of pure ci«- and tran*-OCP*
• A commercial mixture of DCP and pure cis-OCP were also positive with
and without metabolic activation in Salmonella typhimurium strain TA98
(PIeasel, 1977; Sudo et al., 1978; Brooks st al., 1978).
• Sudo et al. (1978) tested OCP in a reverse mutation assay with
B. coll B/r Hp2 with negative results.
• OCP was negative for reverse mutation in the mouse host-mediated test
with £. typhimurium G46 in studies by Shirasu et al. (1976) and Sudo
et alT (1978).
Carcinogenicity
• F344 rats of each sex were gavaged with Telone II in corn oil at
doses of 0, 25 and 50 mg/kg/day for 3 days per week. A total of
77 rats/sex were used for each dose group (52 animals/sex/group were
dosed for 104 weeks in the main oncogenicity study, and an ancillary
study where 5 animals/sex/ group were sacrificed after 9, 16, 21, 24
and 27 months' exposure to OCP). No increased mortality occurred In
treated animals, aaoplastie lesions associated with Telone II Included
squamous cell papillomas of the forestomach (male rats: 1/52; 1/S2i
9/52; female ratsi 0/52; 2/52; 3/52), squamous cell carcinoma* of
the forestomach (male rats: 0/52; 0/52; 4/52) and neoplastic nodule*
of the liver (male rats: 1/52; 6/52; 7/52). The increased incidence
of forestomach tumors was accompanied by a positive trend for fore-
•tomach basal cell hyperplasia in male and female rats of both treated
groups (25 and 50 mg/kg/day). The highest dose level tested in rats
(50 mg/kg/day) approximated a maximum tolerated dose level (NTP, 198S).
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1,3-Oichloroprop«ne August, 1988
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B6C3P) mica of each aax were gavaged with Talon* 11 in corn oil 'at
doses of 0, 50 and 100 ag/kg/day for 104 waeka. A total of SO mice/sex
wars used for each dose group* Ou« to excessive mortality ia control
mala mice from ayocazdlal inflammation approximately 1 year aftar the
initiation of tha study, conclusions partalalng to oncogeniclty ware
baaed on concurrent control data and WP historical control data.
Hsoplaatic laaiona aaaociatad with tha administration of Talone IX
included aquaaous call papillomaa of the foraatomach (female alee:
0/50; 1/50» 2/50), aquamous cell carcinoaac of tha forestoaach (feaale
alee: 0/50; 0/50; 2/50), tranaitional cell earcinomaa of tha urinary
bladder (female aices 0/50; 8/SOi 21/48), and alveolar/bronchlolar
adenoaaa (female alee: 0/50; 3/50} 8/50). the inereaaed incidence
of forastoaach tuaora waa accompanied by an increased incidence of
atoaach epithelial call hyperplaaia in aalea and femalea at the
hlgheat doae level teated (100 ag/kg/day), and tha inereaaed Incidence
of urinary bladder tranaitional call carcinoma waa accompanied by a
positive trend for bladder hyperplaaia in mala and female alee of
both treated groupa (50 and 100 mg/kg/day). Incidences of neoplasms
were not significantly inereaaed in aale mice (NTF, 1985).
Thirty female Ha:ZCR Arias mice received weekly subcutaneous injections
of cis-OCP. the doae was 3 ag OCP/aouae In 0.05 al. trioetanoin
delivered to the left flank. After 77 weeks, there was an inereaaed
incidence of fibrosarcomas at the site of injection. Six of the
30 exposed alee developed the tumors. Thar* were no similar lesions
in the controls (Van Duuren, 1979).
Scott et al. (1987) exposed groupa of aala and female B6C3F1 alee (70
anlaals/sex/doae) to vapors of Telone XI* for 6 hours/day, 5 days/week
for up to 24 months at 0, 5, 20 or 60 ppa. The only tuaorigenic
effect was an Increased incidence in benign lung tumors (bronchio-
loalveolar adenomas) in the 60 ppm exposed males. There were no
tuaorigenlc effects in the lower-dose males or at any of the doses In
females.
Lomax et al. (1987) exposed Fisher 344 rats (70 rats/•ex/dose) to
vapors of Telone IX* (0, 5, 20 and 60 ppa). The two year exposure by
inhalation did not result In increases In timior incidence.
V. QUANTIFICATIOM OF TOXICOLOGICAL EFFECTS
Health advisories (HAs) are generally determined for one-day, ten-day,
longer-ten (up to 7 years) and lifetime exposures if adequate data are
available that identify a aensitive noncarcinogenic end point of toxlcity.
The HAs for noncarcinogenic toxicants are derived using the following formula:
HA . (HOABL or LOAEL) x (BW) » ^/j, , ug/u
(OF) x ( L/day)
where:
NOAEL or LOAEL - Mo- or Lowest-Observed-Adverse-Bffeet Level
in ag/kg bw/day.
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i TJ-QlchloTopropene August,
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BW • assumed body weight of a child (10 kg) or
an adult (70 kg).
OF - uncertainty factor (10, 100, 1,000 or 10,000),
la accordance with Z9\ or NAS/OOU guidelines.
.. _ L/day - assumed daily water consumption of a child
{) Vday) or aa adult (2 L/day).
One-day Health Advisory
There are not sufficient data to derive a One-day Health Advisory value
for DCP. It is recommended that the Longer term HA value for a 10-kg child
(30 ug/L, calculated below) be used at this time as a conservative estimate
of the One-day HA value.
Ten-day Health Advisory
There are not sufficient data to derive a Ten-day HA value for DCP.
It is recommended that the Longer-term BA value for a 10-*g child (30 ug/L.
calculated below) be used as a conservative estimate of the Ten-day HA value.
Longer-term Health Advisory
The Til et al. (1973) 13 weeks subehronlc gavage study in rats has been
selected to serv« as the basis for calculating the Longer-term HA for DCP.
This study resulted in a LOA2L of 10.0 sig/kg/day based on Increased relative
kidney weight in males. No adverse effects were noted at the next lowest
dose (3.0 mg/kg/day). Therefore, the NOAEL is 3.0 mg/kg/day.
Based on the NOAEL of 3.0 mg/kg/day determined in this study, the Longer-
term HAs are calculated as follows:
For a 10-kg child:
Longer-term HA • (3.0 m^/kg/day) (10 k
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',3-Olchloropropena August, 1968
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For • 70-kg adult:
Longer-term HA • <3'° aq/lcq/dav) (70 ko) . 0.105 mg/L (100 ua/L)
(100) (10) (2 L/day) *
where:
3.0 mgAg/dey • NGAEL based on the absence of Increased relative kidney
weights in rats*
70 kg • assumed body weight of an adult.
100 • uncertainty factor, chosen In accordance with EPA or
HAS/ODW guidelines for use with a NGAEL from an animal
study'
10 - Modifying factor, selected since this was the only useful
gavage study available and classified as suppleaentary
data. Also there were considerable toxlcological -data gaps.
.2 I/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^tep process. Step 1 determines the Reference Use
(RfD), formerly called the Acceptable Daily Intake (ADI). The RfO 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 LQAEL), identified from a chronic (or subchroaic) study, divided
by an uncertainty factor(a). From the RfD, a Drinking Hater Equivalent Level
(DUEL) can be determined (Step 2). A OKEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarclnogenic health effects would not be expected to occur.
The DUEL 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. If the contaminant is classified as a Group A or
B carcinogen, according to the Agency's classification scheme of carcinogenic
potential, then caution should be exercised in assessing the risks associated
with lifetime exposure to this chemical. For Group C carcinogens, an additional
safety factor of 10 is added to the DWEL.
The Lifetime HA for a 70-kg adult has been determined on the basis of
the study in rats by Til et al. (1973), as described above.
Using the NQAEL of 3.0 mg/kg/day, as determined in that study, the
DUEL is calculated as follows:
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1,3-Oichloropropene August, 1988
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Btep 1t Dstsrmination of the Reference Dose {RfD)
RfD . (3.0 mg/kq/day) . 0.0003 mgAg/day
(1,000) (10)
where:
3.0 mgAg/day • NOAEL based on the absence of increased relative kidney
weights in rats.
1,000 - uncertainty factor, chosen in accordance with EPA or
NAS/ODH guidelines for use with a NOA£L from an animal
study of less-than•lifetime duration.
10 • modifying factor selected since this was the only useful
gavage study available and classified as supplementary
data. Also there were considerable toxicological data gaps.
Step 2: Determination of the Drinking Hater Equivalent Level (OWED
DWEL • (0-0003 mq/kq/day) (70 kg) . <011 /L (10 /L)
(2 L/day)
where:
0.0003 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 BAs are not recommended for Group A or B carcinogens. DCP is
a Group B2, probable human carcinogen. The estimated cancer risk associated
with lifetime exposure to drinking water containing DCP at 10 ug/L is
approximately 5.0 x 10-3. ihiB estimate represents the upper 95% confidence
limit using the linearized multistage model, the actual risk is unlikely to
exceed this value.
Evaluation of Carcinogenic Potential
• DCP may be classified as a B2, probable human carcinogen baaed on
sufficient evidence of tumor production in two rodent species and two
routes of administration.
8 Data on an increased incidence of squamous cell papilloma or carcinoma
of the forestomach in rats exposed to DCP (NCI, 1985) were used for a
quantitative assessment of cancer risk due to DCP. Based on the data
from this study and using the linearized multistage model, a carcinogenic
potency factor (q^) for humans of 1.75 x 10~* (mgAg/day)*1 was
calculated.
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1,3-Oichloroprop«ne Auguit, 1988
-13-
• The drinking water concentrations corresponding to increased lifetime
cancer risks of 10-4, io-5 and 10-6 (one excess cancer per one million
population) for a 70Hcg adult consuming 2 L/day are 20 ug/L, 2 ug/L
and 0.2 ug/L, respectively.
• The forestomach timwr data in male rats used to calculate the qj*
value (NCI, 1985) consisted of the 2-year study data excluding the
ancillary studies data. The ancilliary studies involved serial
sacrifice of animals (at 9, 16, 21, 24 and 27 months). Zt is not
appropriate to include these data in the lifetime predictive model
used (multistage).
0 For comparison purposes, drinking water concentrations associated
with an excess risk of 10-6 were 0.2 ug/L, 3.6 mg/L, 0.03 ug/L and
0.004 ug/L for the one-hit, Neibull, probit and logit models,
respectively.
VI. OTHER CRITERIA, GDIDANCE AMD STANDARDS
• The ACGZH recommended 1 ppm (5 mg/m*) as a Threshold Limit Value for
DCP (Clayton and Clayton, 1981).
VII. ANALYTICAL METHODS
0 No specific methods have been published by U.S. EPA for analysis of
DCP in water." However, EPA Method 524.2 (U.S. EPA, 1986d) and EPA
Method 502.2 (USBPA, 1986e) both for volatile organic compounds in
water should be suitable for analysis of DCP. Both are standard
purge and trap capillary column gas chromatographlc techniques.
While an estimated detection limit has not been calculated for the
two isomers of 1,3-^lichloropropene, work done with 1,1-^lichloropropene
would indicate a range for 1,3HXP of 0.02 to 0.05 ug/L.
VIII. TREATMENT TECHNOLOGIES
• There are no specific publications on treatment of 1,3-OCP. However,
adequate treatment by granular activated carbon (GAC) should be
possible. Freundlich carbon absorption isotherms for DCP indicate
reasonably high adsorption capacity (U.S. EPA, 1980).
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1,3-0ichloroprop«n« August, 1988
-14-
ZZ. MTEREHCBS
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1,3-Oichloropropene August, 1968
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•Confidential Business Information submitted to the Office of Peeticide
Programs.
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