March 31, 1987
822K87100
STYRENE
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.
-------
Styrene
March 31, 1987
-2-
This Health Advisory (HA) is based on information presented in the
Office of Drinking Water's Health Effects Criteria Document (CD) for Styrene
(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, 5285 Port Royal
Rd., Springfield, VA 22161, PB # 86-118056/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. 100-42-5
Structural Formula
CH . CH.
Sy nony ms
Vinyl benzene, cinnaraene, phenylethylene, ethenylbenzene
Use
Styrene plastics .
Properties (Hansch and Leo, 1979; Lewis et al., 1983)
Chemical Formula
Molecular Weight
Physical State
Melting Point
Density (20°C)
Vapor Pressure (20*C)
(25°C)
Water Solubility
Log Octanol/Water Partition
Coefficient
Conversion Factors
Occurrence
C8H8
104.16
Clear, colorless liquid with a
characteristically sweet and
pleasant odor
145°C
30.86 g/cm3
4.53 torr
6.18 torr
320 mg/L
2.95
0.235 ppm
4.26 mg/m3
1 ppm
Styrene is produced primarily from the dehydrogenation of ethylbenzene,
In 1982, the U.S production of styrene totaled 5.9 billion pounds.
-------
Styrene March 31, 1987
-3-
National drinking water surveys indicate that styrene is an infrequent
contaminant. To date, the testing of 941 ground water supplies and
102 surface water supplies has failed to result in the detection of
a single positive occurrence (Boland, 1981).
Contamination of drinking water by styrene, however, has been reported
occasionally by State programs.
III. PHARMACOKINETICS
Absorption
0 Available data indicate that the absorption of styrene from the
gastrointestinal tract of rats is rapid and virtually complete
(Plotnick and Weigel, 1979).
0 Styrene uptake and absorption has been the subject of a number of
human inhalation studies (Fiserova-Sergerova and Teisinger, 1965;
Teramoto and Horiguchi, 1979). The findings of these studies indicate
that pulmonary retention of styrene is approximately 2/3 of the
administered concentration with considerable variation in measured
uptake between individuals and studies (mean uptakes ranged from
59 to 89%).
Distribution
0 The distribution of styrene following oral administration was studied
in rats given single doses of 20 mg/kg 14C-styrene in corn oil by
gavage (Plotnick and Weigel, 1979). Peak tissue levels were reached
within 2 to 4 hours. The organs with the highest concentrations were
kidney (46 ug/g in males; 25 ug/g in females), liver (13 ug/g in
males; 7 ug/g in females) and pancreas (10 ug/g in males; 6 ug/g in
females) with lower concentration levels in lungs, heart, spleen,
adrenals, brain, testes and ovaries.
0 Results from inhalation studies in rats indicate that distribution of
styrene is widespread with relatively high concentrations in adipose
tissue (Withey and Collins, 1979).
0 In humans, Dowty st al. (1976) found concentrations of transplacent-
ally transferred styrene to be somewhat higher than those of maternal
blood, which suggests a selective one-way transplacental transfer.
0 Pellizzari et al. (1982) detected styrene in each of 8 milk samples
collected from lactating women residing in various cities.
Metabolism
0 The metabolic fate of styrene in mammals has been studied extensively.
There is limited information from human studies, but similarities to
the process in other mammals have been identified.
-------
Styrene March 31, 1987
-4-
Based on studies in rats administered styrene-7,8-oxide or styrene
glycol by intraperitoneal injection, Ohtsuji and Ikeda (1971) have
proposed that the metabolism of styrene proceeds via P-450 microsomal
oxidations to styrene oxide, styrene glycol, and then to mandelic
acid which is metabolized to either phenylglyoxylic acid or to benzoic
the hippuric acid.
Excretion
Results from a. number of studies in rats (Withey and Collins, 1977,
1979; Ramsey and Young, 1978, 1980; Teramoto and Horiguchi, 1979)
indicate that styrene is eliminated relatively rapidly from all
tissues in test animals.
Twenty-four hours following oral administration of 20 mg/kg 14C-
styrene to rats, concentrations in all tissues and organs examined were
less than 1 ug/g (Plotnick and Weigel, 1979).
The elimination of styrene (from the heart, brain, liver, spleen and
kidney o£ rats was described by biphasic log-linear kinetics after
intravenous injection of 4.0 mg/kg (Withey and Collins, 1977). Half-
lives ranged from 3.8 to 7.1 minutes for-the alpha (fast) phase and
from 20 to 37 minutes for the beta (slow) phase.
Predictions based on a toxicokinetic model (parameters estimated from
a human inhalation study) indicated that maximum concentrations of
styrene in both blood and fat of humans were reached after a few
repeated 8-hour daily exposures to 80 ppm styrene, suggesting no
tendency for long-term accumulation (Ramsey et al., 1980; Ramsey and
Young, 1978, 1980).
IV. HEALTH EFFECTS
Humans
Results of controlled experiments using human volunteers indicate
that styrene administered by inhalation at relatively high doses
results in central nervous system (CNS) effects.
Drowsiness, listlessness and an altered sense of balance were
reported during a 4-hour exposure of two male subjects to styrene
at 3,407 mg/m3 (800 ppm) (Carpenter et al., 1944).
Stewart et al. (1968) reported that volunteers exposed to styrene by
inhalation at 217 mg/m3 (50 ppm) and 499 mg/m3 (117 ppm) for 1 and
2 hours, respectively, showed no signs of toxicity. The moderately
~strong initial styrene odor diminished after 5 minutes. At 921 mg/m3
(216 ppm) nasal irritation resulted after 20 minutes. Eye and nose
irritation, strong odor and altered neurological function were reported
for volunteers exposed to styrene at 1,600 mg/m3 (376 ppm) for 1 hour.
Most volunteers exposed to this level exhibited reduced performance
in the Crawford Manual Dexterity Collar and Pin Test, the modified
Romberg Test and the Flannagan Coordination Test. Six subjects were
exposed to 422 mg/m3 (99 ppm) styrene vapor for seven hours. No
serious untowed effects were noted.
-------
Styrene March 31, 1987
» C —
Gamberale and Hultengren (1974) exposed 12 subjects to styrene by
inhalation at concentrations of 213, 639, 1,065 and 1,491 mg/m3 (50,
150, 250 and 350 ppm) during four consecutive 30-minute intervals.
A dose-related increase in single reaction time was evident. Reaction
time recorded during the final 30-minute exposure was significantly
increased (p <0.05).
Odkvist et al. (1982) studied the effects of styrene on the vestibulo-
oculomotor functions in 10 subjects exposed to styrene by inhalation
at 370 to 591 mg/m-3 (88-140 ppm) for approximately 80 minutes. The
rate of movement of the eyes between two alternating light sources
(saccade) increased significantly (p <0.05) after exposure. Suppression
of the vestibule-oculomotor reflex was also affected.
There is suggestive evidence that the human fetus is more sensitive
than the adult to the toxic effects of styrene (Holmberg, 1977;
Hemminki et al., 1980).
The frequency of spontaneous abortions among Finnish chemical workers
was analyzed by Hemminki et al. (1980). Information on spontaneous
abortions (15,482 cases), induced abortions (71,235 cases) and births
(193,897 cases) for 1973-1976 was obtained from the Hospital Discharge
Registry of the Finnish National Board of Health and linked by social
security number to the membership of the Finnish Union of Chemical
Workers (approximately 900 female members). About 85% of the total
number of spontaneous abortions in Finland were reportedly listed in
the registry. The rate of spontaneous abortion was defined as the
number of spontaneous abortions x 100/number of births. The rates
of spontaneous abortion were 8.54% (N = 52) and 15.0% (N = 6) among
the female union members and a subgroup in the styrene industry,
respectively. These rates were significantly higher (p<0.01) than
the rate among all Finnish women (5.52%, 15,482 spontaneous abortions).
The ratios of spontaneous abortion were 16 and 32 in the female union
workers and female styrene industry workers, respectively, which
were significantly higher (p<0.001) than the rate among all Finnish
women (8%).
The information on the work histories of 43 Finnish mothers of children
born with central nervous system (CNS) defects from June 1, 1976 to
March 1, 1977 were obtained through personal interviews (Holmberg,
1977). Two of these mothers had been employed in the reinforced
plastics industry with regular exposure to styrene, polyester resin,
organic peroxides and acetone during pregnancy. The defects in their
two children were anencephaly and congenital hydrocephaly. The
overall rates of anencephaly and congenital hydrocephaly were reported
to be 0.2 and 0.3, respectively, per 1000 live births in Finland.
Based on these estimates, there appeared to be more than a 300 fold
increased rate of thooo malformations—in- the reinforced plastics
industry during the 9-month study period compared with the general
population (2/12 vs 0.5/1000).
-------
Styrene March 31, 1987
-6-
Animals
Short-term Exposure
0 Wolf et al. (1956) reported an acute oral LDgQ °f greater than 5,000
mg/kg for rats treated with styrene by gavage. This indicates that
the acute toxicity of styrene is relatively low.
0 The lowest single oral dose of styrene (administered by oral intuba-
tion) causing 100% mortality in rats within two weeks of treatment
was 8,000 mg/kg, while 1,600 mg/kg was the maximum dose resulting in
no deaths (Spencer et al., 1942).
0 The effects of styrene administration at 250, 450 or 900 mg/kg orally
(method not stated) for 7 consecutive days on hepatic mixed function
oxidase (MFO) enzyme activities, glutathione content and glutathione-
S-transferase activity were reported by Das et al. (1981). Activities
of aryl hydrocarbon hydroxylase and aniline hydroxylase were signifi-
cantly enhanced at higher doses of styrene (450 and 900 mg/kg). A
significant lowering of glutathione content accompanied with the
inhibition of glutathione-S-transferase activity was also noted at
the highest dose of styrene (900 mg/kg). Therefore, the MOAEL for
effects on hepatic enzymes in this study was 250 mg/kg/day.
0 Agrawal et al. (1982) studied the effects of styrene on dopamine
receptor binding in rats. Styrene was administered at 200 or 400
mg/kg/day by gavage to groups of 6 eight-week old ITRC male albino
rats. Styrene was administered in a single dose or in up to 90 daily
doses over 90 days. Significant increases in the specific binding of
•^H-spiroperidol to dopamine receptors in the corpus stratum were
noted at both levels^jif-ter single or repeated exposure to styrene.
The LOAEL for this study was identified as 200 mg/kg/day.
Long-term Exposure
0 Changes in hepatic enzyme activity following oral exposure to styrene
have been demonstrated by a number of investigators.
0 Srivastava et al. (1982) administered styrene by gavage (at 200 or
400 mg/kg/day) to groups of 5 adult male albino ITRC rats, 6 days
per week for 100 days. These animals did not exhibit any changes in
weight gain or other overt signs of toxicity. There were significant
dose-dependent increases in hepatic enzymes (benzo[a]pyrene hydroxylase
and aminopyrine-N-deraethylase) as well as decreases (glutathione-S-
transferase). There were significant decreases in some mitochondrial
enzymes as well. Histopathological changes were seen only at the
high dose and these consisted of tiny areas of focal liver necrosis,
consisting of a few degenerated hepatocytes and inflammatory cells.
Therefore, the LOAEL for hepatic effects was 200 mg/kg/day.
0 Groups of ten female rats were administered styrene at 66.7, 133, 400
or 667 mg/kg/day by intubation, five days a week for six months (Wolf
-------
Styrene March 31, 1987
-7-
et al., 1956). At the two higher dose levels, decreased growth
weights and increased liver and kidney weights were observed without
hematologic or histopathologic effects. At the two lower dose levels,
no effects were noted on body weight, organ weight or pathology.
Therefore, the NOAEL for this study was 133 mg/kg/day and the LOAEL
was 400 mg/kg/day.
0 Beagle dogs were given styrene in a peanut oil suspension by gavage
7 days per week for 560 days (Quast et al., 1978). Dose levels were
200, 400 or 600 mg/kg bw/day. The controls received peanut oil only.
At the two higher dose levels, minimal histopathologic effects were
noted in the liver (increased iron deposits within the reticulo-
endothelial cells) as well as hematologic effects that included
increased Heinz bodies in erythrocytes and a decreased packed cell
volume. At the lowest dose level, these effects were not noted.
Therefore, 200 mg/kg/day was identified as the NOAEL for this study
and 400 mg/kg/day can be designated as the LOAEL.
Reproductive Effects
0 The reproductive/teratogenic effects of styrene oxide were assessed
in Wistar rats (Sikov et al. 1981). The percentage of pregnant rats
was reduced significantly.
Developmental Effects
0 Investigators at the Dow Chemical Company administered styrene in
peanut oil to pregnant Sprague-Dawley rats (29 to 39 dams per group)
by gavage at dose levels of 0, 180 or 300 mg/kg/day (0, 90, 150 mg/kg
twice daily) on days 6 through 15 of gestation (Murray et al., 1976;
1978). Maternal toxicity was indicated by significantly, red.useji—
(p <0.05) body weight gain and food consumption at the higher dose
level. There were no significant effects observed on maternal
mortality or percent pregnancy. No teratogenic or fetotoxic effects
were observed. Therefore, the NOAEL for maternal toxicity was 180
mg/kg/day.
Mutagenici ty
0 Results were negative for six mutagenicity tests using Salmonella
typhimurium test systems, both with and without S-9 metabolic activat-
ing system. Styrene was tested using the bacterial strains TA1535,
TA1537, TA98 and TA100. De Meester et al. (1977, 1981) and Vainio
et al. (1976) obtained positive results with mutant strains sensitive
to base pair substitution while all tests were negative in strains
sensitive to frameshift mutagens.
0 Styrene oxide, a major metabolite of styrene, has been demonstrated
consistently to be mutagenic in S_. typhimurium TA1535 and TA100,
in the presence and absence of a mammalian metabolic activating
system (De Meester et al., 1977; 1981).
-------
Styrene March 31, 1987
-8-
Carcinogenici ty
0 Both positive and negative results have been reported in bioassays
of the potential carcinogenicity of styrene in experimental animals.
Most of the long-term bioassay results, however, are characterized by
inconsistent observations of elevated tumor formation and excessive
mortality among treated animals (Jersey et al., 1978; Ponomarkov
and Tomatis, 1978; NTP, 1979; Maltoni et al., 1982).
0 Retrospective cohort mortality and case-control studies have btien con-
ducted on workers exposed to styrene in the styrene-polystyrene manu-
facturing industry and in the styrene-butadiene synthetic rubber industry
(McMichael et al., 1976; Smith and Ellis, 1977; Meinhardt et al., 1978).
There are inadequate data at present to indicate that styrene is a
human carcinogen. However, an elevated incidence of tumors of the
hematopoietic and lymphatic tissues have been observed. The available
studies are limited because of relatively small cohort sizes or
multiple chemical exposures of workers (including exposure to benzene).
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories (HAs) are generally determined for One-day, Ten-day,
Longer-term (approximately 7 years) and Lifetime exposures if adequate data
are available that identify a sensitive noncarcinogenic end point of toxicity.
The HAs for noncarcinogenic toxicants are derived using the following formula:
HA = (NOAEL or LOAEL) x (BW) = mg/L ( ug/L)
(UF) x ( L/day)
where:
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in mg/kg bw/day.
BW = assumed body weight of a child (10 kg) or
an adult (70 kg).
UF =» uncertainty factor (10, 100 or 1,000), in
accordance with NAS/ODW guidelines.
L/day = assumed daily water consumption of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
The study of Stewart et al. (1968) was seleted as the basis for calculating
the One-day HA. The study invloved a controlled styrene inhalation exposure
using nine healthy human male volunteers. No subjective or objective signs
of toxicity were noted following one and two hour exposures to 51 ppm (217
mg/m3) or 117 ppm (449 mg/m3) styrene respectively. To simluate a work
day, six subjects were exposed to 99 ppm (422 mg/m3) styrene vapor for seven
-------
Styrene March 31, 1987
-9-
hours. From a subjective standpoint, no serious untoward effects were noted except
mild eye and throat irritation in three subjects. There were no objective
signs of impairment of balance or coordination; however, three of the six
subjects did report that they were having intermittent difficulty in performing
the modified Romberg Test. In contrast, exposure to 376 ppm (1602 mg/m3)
styrene vapor for one hour resulted in abnormal neurological findings and
complaints of nausea and inebriation. The result of urinalysis, hematology
and blood chemistry studies were normal and unchanged from pre-exposure
values.
The results of another study (Odkvist et al., 1982) using human volunteers
exposed to similar styrene levels, indicate that the mean pulmonary styrene
uptake was 64% of the inspired amount. Using a NOAEL of 99 ppm (422 mg/m3)
from a 7-hour exposure, the One-day Health Advisory for a 10-kg child can be
derived. First the total absorbed dose (TAD) is determined.
TAD* = (422 mg/m3) (20 m3/day) (7 hours/24 hours) (0.64) =22.5 mg/kg/day
70 kg
whe re:
TAD = total absorbed dose.
442 mg/m3 = NOAEL, based on the absence of adverse effects in
humans exposed to styrene by inhalation.
7 hours/24 hours = duration of exposure.
20 m3/day = assumed ventilation volume for 70-kg adult.
0.64 = estimated ratio of absorbed dose (Odkvist et al., 1982).
70 kg = weight of exposed individual (adult).
Therefore the One-day Health Advisory for a 10-kg child is as follows:
One-day HA = (22.5 mg/kg/day) (10 kg) =22.5 mg/L
(10) (1 L/day)
where:
22.5 mg/kg/day = TAD.
10 kg = assumed body weight of a child.
10 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from a study in humans.
1 L/day = assumed daily water consumption of a child.
-------
Styrene March 31, 1987
-10-
Ten-day -Health Advisory
No information was found in the available literature that was suitable
for deriving a Ten-day HA value for styrene. It is therefore recommended
that the Longer-term HA for a 10-kg child (2 mg/L, calculated below) be
used at this time as a conservative estimate of the Ten-day HA value.
Longer-term Health Advisory
The Quast et al. (1978) study in dogs has been chosen to serve as the
basis for calculating the Longer-term HAs for styrene. In this study, beagle
dogs were administered styrene by gavage at 0, 200, 400 or 600 mg/kg/day,
7 days per week, for 560 days. At the two higher doses, minimal histopathologic
effects were noted in the liver (increased iron deposits within the reticulo-
endothelial cells) as well as hematologic effects that included increased
Heinz bodies in erythrocytes and a decreased packed cell volume. At the
lowest dose level, these effects were not noted with the possible exception of the.
equivocal observation of low level occurrence of Heinz bodies in a single
female from this group.
Based on the NOAEL of 200 mg/kg/day determined in this study, the Longer-
term HAs are calculated as follows:
For a 10-kg child:
Longer-term HA = (200 mg/kg/day) (10 kg) = 2 mg/L (2000 ug/L)
(100) (10) (1 L/day)
where:
200 mg/kg/day = NOAEL at which no decreased growth weights or increased
liver and kidney weights were observed in dogs.
10 kg - assumed body weight of a child.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
10 = modifying factor for small group size (4 dogs per
treatment).
1 L/day = assumed daily water consumption of a child.
For a 70-kg adult:
Longer-term HA = (200 mg/kg/day) (70 kg) = 7 mg/L (7000 ug/L)
(100) (10) (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.
-------
Styrene March 31, 1987
-11-
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, 1986), 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 s'tudy in dogs by Quast et al. (1978) as described above.
Using the NOAEL of 200 mg/kg/day, as determined in that study, the
Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (200 mg/kg/day) . 0 2 mg/kg/day
(1,000)
where:
•
200 mg/kg/day = NOAEL at which no decreased growth weights or increased
liver and kidney weights were observed in dogs.
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study
of less-than-lifetime duration.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.2 mg/kg/day) (70 kg) = o.7 mg/L (700 ug/L)
(2 L/day) (10)
-------
Styrene March 31 , 1987
-12-
where:
0.2 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 » (7 mg/L) (20%) - 0.14 mg/L (140 ug/L)
(10)
where:
7 mg/L » DWEL.
20% = assumed relative source contribution from water.
10 = additional uncertainty factor per ODW policy to
account for possible carcinogenicity.
Evaluation of Carcinogenic Potential
0 Data on an increased incidence of lung tumors (adenomas and carci-
nomas) in 020 strain mice (Ponomarkov and Tomatis, 1978) were used
for the quantitative assessment of cancer risk due to styrene.
Based on the data from this study and using the linearized
multistage model, a carcinogenic potency factor (qi*) for humans of
1.34 (mg/kg/day)~1 was calculated from the data for male mice and a
q1 * of 2.47 (mg/kg/day)~1 was calculated from the data for female mice
(Ponomarkov and Tomatis, 1978). Because the data cannot accommodate
a tumor incidence of 100% when only a single dose is tested, the
tumor response for female mice was adjusted from 32/32 and the
transformed dose reduced by multiplying the calculated transformed
dose, 25.7 mg/kg/day, by the ratio 31/32 to arrive at an adjusted
transformed dose of 24.9 mg/kg/day. The higher of the two q-,* values
is the basis for the estimation of cancer risk levels. The doses
corresponding to increased lifetime cancer risks of 10~4, 10~5 and
10-6 for a 70-kg adult are 3 x 10~3, 3 x 10~4, 3 x 10~5 mg/kg/day,
respectively. Assuming a water consumption of 2 liters/day, the
corresponding concentrations of styrene in water are 1.4, 1.4 x 10~1
and 1.4 x 10~2 ug/L, respectively. These criteria, which reflect
lifetime exposure, are uncertain because of short exposure duration
(13% of lifetime) and the small number of animals in each dose group.
0 IARC evaluated styrene -in February of 1979 and found insufficient
evidence to reach a conclusion as to its carcinogenicity rating
(IARC, 1979).
• Applying the criteria described in EPA's guideline for assessment of
carcinogenic risk (U.S. EPA, 1986), styrene may be classified in
Group C: Possible human carcinogen. This category is for agents with
limited evidence of carcinogenicity in animals in the absence of human
data.
-------
Styrene March 31, 1987
-13-
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 The OSHA Standard for styrene is an 8-hour TWA concentration of 100 ppm,
a ceiling concentration of 200 ppm and a maximum peak concentration
(29 CFR 1910.1000; Table Z-2) of 600 ppm for 5 minutes or less in any
3-hour period.
0 The ACGIH (1982) has established the TWA-TLV for styrene in workroom
air as 50 ppm with an STEL of 100 ppm. The TLV was reduced from 100
ppm in 1981 (ACGIH, 1981).
0 NIOSH (1983) recommended a styrene concentration limit in workplace
air of 50 ppm TWA for up to a 10-hour day, 40 hour work-week and a
ceiling concentration 100 ppm determined during any 15 minute sampling
period.
VII. ANALYTICAL METHODS
0 Styrene content is determined by a purge-and-trap gas chromatographic
procedure used for the determination of volatile aromatic and unsat-
urated organic compounds in water (U.S. EPA, 1985b). This method
calls for the bubbling of an inert gas through the sample and trapping
styrene on an adsorbant material. The adsorbant material is heated
to drive off styrene onto a gas chromatographic column which is
temperature programmed to separate the method analytes which are then
detected by"the photoionization detector. This method is applicable
to the measurement of styrene over a concentration range of 0.05 to
1,500 ug/L, Confirmatory analysis for styrene is by mass spectrometry
which has a detection limit of 0.3 ug/L (U.S. EPA, 1985c).
VIII. TREATMENT TECHNOLOGIES
0 Information is available on the removal of styrene from water by air
stripping, adsorption and oxidation. Styrene has a Henry's Law
Constant of 12 atm which makes it suitable for removal from water by
air stripping (U.S. EPA, 1985d).
8 Decarbonaters which have some aeration function have been evaluated
for their efficacy in styrene removal. When the influent styrene
concentration was 0.076 ug/L, the decarbonators tested were able to
remove 51.3% (U.S. EPA, 1985d).
0 Tests evaluating adsorption of styrene by granular activated carbon
showed that an average of 40% was removed over a 10-month period
(U.S. EPA, 1985d). The influent styrene concentration was 0.03 ug/L.
0 The ethenyl double bond found in the styrene molecule makes it amend-
able to oxidation. It is, therefore, possible that oxidative tech-
niques may be effective in removing styrene from potable water. Bench
scale evaluations of ozone treatment of styrene-contaminated water
•: conducted by Avigne (1983, as cited by U.S. EPA, 1985b) indicate
that the reaction rate constant for a 0.007 mM styrene solution (pH
2) is 300,000 L/mole-sec. The pH was maintained at 2 to inhibit the
-------
Styrene March 31, 1987
-14-
decomposition of ozone. Oxidation of styrene to benzaldehyde and
hydrogen peroxide was reported by Legube (1983, as cited by U.S. EPA,
1985b). Using an ozone application rate of 10' mg/hr at 12 L/hr
0.9 moles ozone per mole of styrene was required to completely oxidize
the styrene. The initial styrene concentration was 1.1 x 10~4 mole/L.
It was suggested that further oxidation of benzaldehyde to benzoic
acid might occur.
0 It is possible that other oxidizing agents such as permanganate could
be effective in oxidizing styrene. However, no studies of tests of
these alternative oxidizing situations were available.
-------
Styrene March 31, 1987
-15-
IX. REFERENCES
ACGIH. 1981. American Conference of Governmental Hygienists. TLVs. Threshold
limit values for chemical substances and physical agents in the workroom
environment with intended changes for 1981. Cincinnati, OH. p. 50.
ACGIH. 1982. American Conference of Governmental Hygienists. TLVs. Threshold
limit values for chemical substances and physical agents in the Workroom
environment with intended changes for 1982. Cincinnati, OH. p. 29.
Agrawal, A.K., S.P. Srivastava and P.K. Seth. 1982. Effect of styrene on
dopamine receptors. Bull. Environ. Contam. Toxicol. 29(4):400-403.
Boland, P.A. 1981. National screening program for organics in drinking
water. EPA contract 68-01-4666. SRI International.
Carpenter, C.P., C.B. Shaffer, C.S. Weil and H.F. Smyth. 1944. Studies on
the inhalation of 1:3-butadiene with a comparison to its narcotic effect
with benzol, toluol and styrene, and a -note on the elimination of styrene
by the human. J. Ind. Hyg. Toxicol. 26(3):69-78.
Das, M., R. Di'Xit, M. Mushtaq, S.P. Srivastava and P.K. Seth. 1981. Effect
of styrene on hepatic mixed function oxidasaes, glutathione content and
glutathione-S-transferase activity in rats. Drug Chem. Toxicol.
4(3):219-227.
De Meester, C., F. Poncelet, M, Roberfroid, J. Rondelet and M. Mercier. 1977.
Mutagenicity of styrene and styrene oxide. Mutat. Res. 56(2):147-152.
De Meester, C., M. Durverger-Van Bogaert, M. Lambotte-Vandepaer, M. Mercier
and F. Poncelet. 1981. Mutagenicity of styrene in the Salmonella
typhimurium test system. Chem. Biol. Interact. 20(2):163-170.
Dowty, B.J., J.L. Laseter and J. Storer. 1976. Transplacental migration and
accumulation in blood of volatile organic constituents. Pediatr. Res.
10:696-701.
Fiserova-Bergerova, V., and Teisinger. 1965. Pulmonary styrene vapor retention.
Ind. Med. Surg. 34:620-622.
Gamberale, F., and M. Hultengren. 1974. Exposure to styrene. II. Psycholog-
ical functions. Work Environ. Health 11(2):86-93.
Hansch, C., and A.J. Leo. 1979. Substituent constants for correlation
analysis in chemistry and biology. John Wiley and Sons, New York, NY.
Hemminki, K., E. Franssila and H. Vainio. 1980. Spontaneous abortion among
female chemical workers in Finland. Int. Arch. Occup. Health 45:123-126.
Holmberg, P.C. 1977. Central nervous defects in two children of mothers
exposed to chemicals in the reinforced plastics industry. Scand. J.
Work Environ. Health 5:333-335.
-------
Styrene March 31, 1987
-16-
IARC. 1979. International Agency for Research on Cancer. IARC monographs
on the evaluation of the carcinogenic risk of chemicals to humans. Some
monomers, plastics and synthetic elastomers, and acrolein. 19, 97-115.
Jersey, G., M. Balmer, J. Quast et al. 1978. Two year chronic inhalation
toxicity and carcinogenicity study on monomeric styrene in rats. Dow
Chemical study for Manufacturing Chemical Association. December 6.
Lewis, P.J., C. Hagopian and P. Koch. 1983. Styrene. In; Kirk-Othmer
Encyclopedia of Chemical Technology, 3rd ed. M. Grayson and D. Eckroth,
eds. John Wiley and Sons, Inc. New York. Vol. 21, pp. 770-801.
Maltoni, C., A. Cilberti and D. Carrietti. 1982. Experimental contributions
in identifying brain potential carcinogens in the petrochemical industry.
Ann. New York Acad. Sci. 381:216-249.
McMichael, A.J., R. Spirtas, J.F. Gamble and P.M. Tousey. 1976. Mortality
among rubber workers: Relationship to specific jobs. J. Occup. Med.
18:178-185.
Meinhardt, T., R. Young and R. Hartle. 1978. Epidemiologic investigations
of styrene-butadiene rubber production and reinforced plastic production.
Scand. J. Work Environ. Health. 8(4):250-259.
Murray, F.J., J.A. John, H.D. Haberstoh et al. 1976. Teratologic evaluation
of styrene monomers administered rats by gavage. Dow Chemical Study for
Manufacturing Chemical Association. August 26.
Murray, F.J., J.A. John, M.F. Balmer and B.A. Schwetz. 1978. Teratologic
evaluation of styrene given to rats and rabbits by inhalation or by
gavage. Toxicology 11(4):335-343.
NIOSH. 1983. National Institute for Occupational Safety and Health. Criteria
for a recommended standard ... occupational exposure to styrene. DHHS
(NIOSH) Publ. No. 83-119. U.S. DHHS, Cincinnati, OH.
NTP. 1979. National Toxicology Program. National Cancer Institute Carcino-
genesis Technical Report Series No. 185. Bioassay of styrene for possible
carcinogenicity.
Odkvist, L.M., B. Larsby, R. Tham et al. 1982. Vestibule-oculomotor disturb-
ances in humans exposed to styrene. Acta Oto-Laryngol. 94(5-6):487-493.
Ohtsuji, M., and M. Ikeda. 1971. Metabolism of styrene in the rat and the
stimulatory effect of phenobarbital. Toxicol. Appl. Pharmacol.
18(2):321-328.
Pellizzari, E.D., T.D. Hartwell, B.S.H. Harris, R.D. Waddell, D.A. Whitaker
and M.D. Erickson. 1982. Purgeable organic compounds in mother's milk.
Bull. Environ. Contam. Toxicol. 28(3):322-328.
Plotnick, H.B., and W.W. Weigel. 1979. Tissue distribution and excretion of
1^-C-styrene in male and female rats. Res. Commun. Chem. Pathol. Pharmacolf
24(3):515-524.
-------
Styrene March 31, 1987
-17-
Ponomarkov, V.I., and L. Tomatis. 1978. Effects of long-term oral administra-
tion of styrene to mice and rats. Scand. J. Work Environ. Health.
4(Suppl.2):127-135.
Quast, J.F., R.P. Kalnins, K.J. Olson, et. al. 1978. Results of a toxicity
study in dogs and teratogenicity studies in rabbits and rats administered
monomeric styrene. Toxicol. Appl. Pharmacol. 45:293-294.
Ramsey, J.C., and J.D. Young. 1978. Pharmacokinetics of inhaled styrene in
rats and humans. Scand. J. Work and Health 4(Suppl.2)-.84-91 .
Ramsey, J.C., and J.D. Young. 1980. Comparative pharmacokinetics of inhaled
styrene in rats and humans. In; Proc. 10*-" Conference on Environmental
Toxicology, OH. November, 1979. AFAMRL-TR-79-121. Wright Patterson Air
Force Base, OH. pp. 103-117.
Ramsey, J.C., J.D. Young, R.J. Karbowski, M.B. Chenoweth, L.P. McCarty and
W.H. Braun. 1980. Pharmacokinetics of inhaled styrene in human
volunteers. Toxicol. Appl. Pharmacol. 53(1):54-63.
Sikov, M.R., W.C. Cannon, D.B. Carr, R.A. Miller, L.F. Montgomery and D.W.
Phelps. 1981. Teratologic Assessment of butylene oxide, styrene oxide
and methyl bromide. Study performed by Battelle Pacific Northwest
Laboratory, Richland, W.A. for National Institute of Occupational Safety
and Health, Division of Biochemical and Behavioral Science, Experimental
Toxicol. Branch, Cincinnati, OH. DHHS (NIOSH) Publ. No. 81-124.
Smith, A.H., and L. Ellis. 1977. Styrene butadiene rubber synthetic plants
and leukemia (letter to the editor). J. Occup. Med. 19(7):441.
Spencer, H.C., D.D. Irish, E.M. Adams and V.K. Rowe. 1942. The response of
laboratory animals to monomeric styrene. J. Ind. Toxicol. 24(10):295-301.
Srivastava, S.P., M. Das, M. Mushtaq, S.V. Chandra and P.K. Seth. 1982.
Hepatic effects of orally administered styrene in rats. J. Appl. Toxicol.
2(4):219-222.
Stewart, R.D., H.c. Dodd, E.D. Baretta and A.w. Schaffer. 1968. Human expo-
sure to styrene vapor. Arch. Environ. Health 16(5):656-662.
Teramoto, K., and S. Horiguchi. 1979. Absorption, distribution and elimination
of styrene in man and experimental animals. Arch. Hig. Rada Toksikol.
30(Suppl):431-439.
U.S. EPA. 1985a. U.S. Environmental Protection Agency. Draft health effects
criteria document for styrene. Office of Drinking Water.
U.S. EPA. 1985b. U.S. Environmental Protection Agency. Method 503.1.
Volatile aromatic organic compounds in water by purge and trap gas
chromatography. Environmental Monitoring and Support Laboratory,
Cincinnati, Ohio 45268.
U.S. EPA. 1985c. U.S. Environmental Protection Agency. Method 524.1.
Volatile organic compounds in water by purge and trap gas chromatography/
mass spectrometry. Environmental Monitoring and Support Laboratory,
Cincinnati, Ohio 45268.
-------
Styrene March 31, 1987
-18-
U.S. EPA. 1985d. U.S. Environmental Protection Agency. Draft technologies
and costs for removal of synthetic organic chemicals from portable water
supplies. Science and Technology Branch, CSD, ODW, U.S. EPA Washington,
D.C.
U.S. EPA. 1986. U.S. Environmental Protection Agency. Guidelines for
carcinogen risk assessment. Federal Register. 51(185):33992-34003.
September 24.
Vainio, H., R. Paakonen, K. Ronnholm, V. Raunio and O Pelkonen. 1976. A study
on the mutagenic activity of styrene and styrene oxide. Scand. J. Work
Environ. 3:147-151.
Withey, J.R., and P.G. Collins. 1977. Pharmacokinetics and distribution of
styrene monomer in rats after intravenous administration. J. Toxicol.
Environ. Health 3(5-6):1011-1120.
Withey, J.R., and P.G. Collins. 1979. The distribution and pharmacokinetics
of styrene monomer in rats by the pulmonary route. J. Environ. Pathol.
Toxicol. 2(6):1329-1342.
Wolf, M.A., V.K. Rowe, D.D. McCollister, R.L. Hollingsworth and F. Oyen. 1956C
Toxicological studies of certain alkylated benzene and benzene. Arch.
Ind. Health 14:387-398.
------- |