Toxicity Profiles
Toxicity Summary for AROCLOR-1254
NOTE:
Although the toxicity values presented in these toxicity profiles
were correct at the time they were produced, these values are subject to change.
Users should always refer to the
Toxicity Value Database
for the current toxicity values.
 Download a WordPerfect version of this toxicity profile. Please note that this document has been saved in WordPerfect 5.1/5.2 for greater accessibility but may have been originally formatted in later versions of WordPerfect (i.e., WordPerfect 6.1, Suite 7, etc.); therefore, formatting changes (i.e., Contents and Page Numbering) may occur when downloading this document.
- EXECUTIVE SUMMARY
- 1. INTRODUCTION
- 2. METABOLISM AND DISPOSITION
- 2.1 ABSORPTION
2.2 DISTRIBUTION
2.3 METABOLISM
2.4 EXCRETION
- 3. NONCARCINOGENIC HEALTH EFFECTS
- 3.1 ORAL EXPOSURES
3.2 INHALATION EXPOSURES
3.3 OTHER ROUTES OF EXPOSURE
3.4 TARGET ORGANS/CRITICAL EFFECTS
- 4. CARCINOGENICITY
- 4.1 ORAL EXPOSURES
4.2 INHALATION EXPOSURES
4.3 OTHER ROUTES OF EXPOSURE
4.4 EPA WEIGHT-OF-EVIDENCE
4.5 CARCINOGENICITY SLOPE FACTORS
- 5. REFERENCES
Prepared by C. B. Bast, Ph.D., D.A.B.T., Chemical Hazard Evaluation Group, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee.
Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM
*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.
EXECUTIVE SUMMARY
Aroclor® 1254 is a polychlorinated biphenyl (PCB) mixture containing approximately 21%
C12H6Cl4, 48% C12H5Cl5, 23% C12H4Cl6, and 6% C12H3Cl7 with an average chlorine content of 54%
(USAF 1989). PCBs are inert, thermally and physically stable, and have dielectric properties. In the
environment, the behavior of PCB mixtures is directly correlated to the degree of chlorination.
Aroclor® is strongly sorbed to soil and remains immobile when leached with water; however, the
mixture is highly mobile in the presence of organic solvents (USAF 1989). PCBs are resistant to
chemical degradation by oxidation or hydrolysis. However, biodegradation, especially of lower
chlorinated PCBs, can occur (USAF 1989). PCBs have high bioconcentration factors, and due to
lipophilicity, especially of highly chlorinated congeners, tend to accumulate in the fat of fish, birds,
mammals, and humans (ATSDR 1995).
PCBs are absorbed after oral, inhalation, or dermal exposure and are stored in adipose tissue.
The location of the chlorine atoms on the phenyl rings is an important factor in PCB metabolism and
excretion. The major route of PCB excretion is in the urine and feces; however, more important is
the elimination in human milk. Metabolites are predominately found in urine and bile, while small
amounts of the parent compound are found in the feces. Biliary excretion appears to be the source
of fecal excretion (ATSDR 1995).
Accidental human poisonings and data from occupational exposure to PCBs suggest initial
dermal and mucosal disturbances followed by systemic effects that may manifest themselves several
years post-exposure. Initial effects are enlargement and hypersecretion of the Meibomian gland of
the eye, swelling of the eyelids, pigmentation of the fingernails and mucous membranes, fatigue, and
nausea. These effects were followed by hyperkeratosis, darkening of the skin, acneform eruptions,
edema of the arms and legs, neurological symptoms, such as headache and limb numbness, and liver
disturbance (USAF 1989).
Hepatotoxicity is a prominent effect of Aroclor® 1254 that has been well characterized
(EPA 1995a). Effects included hepatic microsomal enzyme induction, increased serum levels of
liver-related enzymes indicative of hepatocellular damage, liver enlargement, lipid deposition,
fibrosis, and necrosis. Groups of 16 adults (11.1 +/-4.1 years at study initiation) female rhesus
monkeys ingested gelatin capsules containing 0, 0.005, 0.02, 0.04, or 0.08 mg/kg/day Aroclor® 1254
daily for more than 5 years (Arnold et al. 1993 a,b; Truelove et al. 1990). Increases in the incidence
of inflamed and/or prominent Meibomian glands; increased incidences of ocular exudate; changes
in finger and/or toe nails; decreases in IgG and IgM antibody levels; decreases in the percent of
helper T-lymphocytes; increases in suppressor T-lymphocyte count; a decrease in helper/suppressor
ratio; and decreases in reticulocyte count, serum cholesterol, total bilirubin, and alpha-1+ alpha-2-globulins were observed in treated monkeys. A chronic oral reference dose (RfD) of
2E-05 mg/kg/day for Aroclor® 1254 was calculated from a lowest-observed-adverse-effect level
(LOAEL) of 0.0005 mg/kg/day derived from the above study (EPA 1995a). The subchronic oral RfD
is 5E-05 mg/kg/day (EPA 1995b).
Data are suggestive but not conclusive concerning the carcinogenicity of PCBs in humans. The
EPA has not determined a weight-of-evidence classification or slope factor for Aroclor® 1254
specifically. However, hepatocellular carcinomas in three strains of rats and two strains of mice have
led the EPA (1995c) to classify PCBs as group B2, probable human carcinogen. The carcinogenicity
slope factor (q1*) for oral exposure to PCBs is 7.7 (mg/kg/day)-1 based on an increase of
hepatocellular tumors in female Sprague-Dawley rats treated with Aroclor® 1260. A drinking water
unit risk of 2.2E-4 (g/L)-1 for PCBs was calculated based on the q1* (EPA 1995c).
1. INTRODUCTION
Aroclor® 1254 (CAS registry number 11097-69-1) is a viscous, light yellow liquid with an
average molecular weight of 328 (USAF 1989). It is a polychlorinated biphenyl (PCB) mixture
containing approximately 21% C12H6Cl4, 48% C12H5Cl5, 23% C12H4Cl6, and 6% C12H3Cl7 with an
average chlorine content of 54% (USAF 1989). PCBs, including Aroclor® 1254, are inert, thermally
and physically stable, and have dielectric properties. They have been used in closed systems such
as heat transfer liquids, hydraulic fluids and lubricants, and in open systems such as plasticizers,
surface coatings, inks, adhesives, pesticide extenders, and for microencapsulation of dyes for
carbonless duplicating papers. The use of PCBs in the United States was limited to closed systems
in 1974, and in February 1977, the U.S. Environmental Protection Agency (EPA) issued final
regulations prohibiting PCB discharge into waterways (EPA 1977). The Monsanto Corporation was
the major U.S. producer of PCBs from 1930 to 1977 and marketed the mixtures under the trade name
Aroclor® (ATSDR 1995).
In the environment, the behavior of PCB mixtures is directly correlated to the chlorination. In
general, as the chlorination increases, sorption increases and transport and transformation decrease
(USAF 1989). Aroclor® is strongly sorbed to soil and remains immobile when leached with water;
however, the mixture is highly mobile in the presence of organic solvents (USAF 1989).
Water-borne PCBs not sorbed to sediment or suspended solids can readily volatilize due to low
water solubility. PCBs are resistant to chemical degradation by oxidation or hydrolysis. However,
biodegradation, especially of lower chlorinated PCBs, can occur (USAF 1989). PCBs have high
bioconcentration factors, and due to lipophilicity, especially of highly chlorinated congeners, tend
to accumulate in the fat of fish, birds, mammals, and humans (ATSDR 1995). In humans, relatively
greater amounts of PCBs have also been identified in skin, liver, and breast milk (ATSDR 1995).
2. METABOLISM AND DISPOSITION
2.1 ABSORPTION
PCBs are well absorbed after oral, inhalation, or dermal exposure (ATSDR 1995). Specific
information concerning absorption of Aroclor® 1254 is limited. Pregnant ferrets administered a
single oral dose of 0.06 mg/kg Aroclor® 1254 absorbed 85% of the administered dose
(Bleavins et al. 1984). Rats, mice, and monkeys absorb between 75 to >90% of orally administered
doses of PCBs (EPA 1995). Oral exposure through consumption of contaminated food (including
breast milk) is the major route of exposure to PCBs for the general population. Populations living
near hazardous waste sites may be orally exposed via consumption of contaminated water or soil
(ATSDR 1995). Both the inhalation and dermal routes of exposure are recognized as significant
contributors of PCB accumulation in occupationally exposed individuals. Quantitative data
concerning inhalation exposure to PCBs are not available. Percutaneous absorption of Aroclor® 1254
through the abdominal skin of monkeys was 20.8% from mineral oil and 14.6% from
trichlorobenzene. Percutaneous absorption of Aroclor® 1254 in monkeys from soil was 14.1% of the
applied dose (ATSDR 1995).
2.2 DISTRIBUTION
Because of lipophilicity, PCBs accumulate mainly in fatty tissue, including breast milk.
Long-term distribution of all PCBs in tissue follows the order
adipose tissue> skin> liver >muscle
(Safe 1980). Growing pigs were orally administered a 7-day total dose of Aroclor® 1254; lower
chlorinated congeners reached peripheral fat more rapidly than higher chlorinated congeners
(Hansen et al. 1977). The highest concentration of chlorinated hydrocarbon residues 24 hours after
gavage administration of a single 1600 mg/kg dose of Aroclor® 1254 to female rats was found in fat,
followed by kidney, liver, and brain. When male and female rats were given oral doses of
73 mg/kg/day Aroclor® 1254 for 98 days, fat tissue had the highest residue concentration followed
by muscle and liver (Curley et al. 1971).
2.3 METABOLISM
Metabolism of PCBs depends on the number and position of the chlorine atoms on the phenyl
ring of the congeners and on the animal species. The metabolism of PCBs following oral and
parenteral exposure has been well characterized, and although limited data are available concerning
metabolism after inhalation and dermal exposure, no data exist to suggest that PCBs would be
metabolized differently by these routes (EPA 1995a). PCBs are metabolized by the microsomal
monooxygenase system catalyzed by cytochrome P-450 to polar metabolites that can undergo
conjugation with glutathione and glucuronic acid (ATSDR 1995). Experimental animal data suggest
the following concerning PCB metabolism: (1) hydroxylation is favored at the para position in the
least chlorinated phenyl ring unless this site is sterically hindered; (2) in the lower chlorinated
biphenyls, the para position of both biphenyl rings and carbon atoms that are para to the chloro
substituent are all readily hydroxylated; (3) the availability of two adjacent unsubstituted carbon
atoms facilitates oxidative metabolism of the PCB substrate; (4) as the degree of chlorination on
both phenyl rings increases, the rate of metabolism decreases; and (5) the metabolism of specific
PCB congeners by different species can result in considerable variations in metabolite distribution
(Safe 1980). The major hydroxylated PCB metabolite in rat plasma after oral administration of
Aroclor® 1254 is 4-hydroxy-2,3,3",4",5-pentachlorobiphenyl. From days 1 to 14 after exposure, the
concentration of this metabolite is 7 to 10 times higher than the concentration of the major congener,
2,2',4,4',5,5'-hexachlorobiphenyl (Bergman et al. 1994).
2.4 EXCRETION
The major route of PCB excretion is in the urine and feces; however, of more importance is
elimination in human milk. Predominately metabolites are found in urine and bile, and small
amounts of parent compound are found in the feces. Biliary excretion appears to be the source of
fecal excretion (ATSDR 1995). The location of the chlorine atoms on the phenyl rings is an
important factor in PCB excretion. Experimental studies in mice suggest that differential
biotransformation results in compounds having at least one pair of unsubstituted adjacent ortho-meta
carbon atoms being excreted faster than those with other configurations, regardless of the number
of chlorine atoms (Gage and Holm 1976). Studies in rats have shown that at equilibrium,
chlorobiphenyl congeners are eliminated from tissues according to individual kinetic parameters.
In rats given six weekly doses of PCBs, di- and trichlorobiphenyls had elimination half lives of 1
to 2 days; tetrachlorobiphenyls had two elimination constants, one between 2 and 10 days and a
second of < 90 days; and penta- and hexachlorobiphenyls had single elimination half-lives of > 90
days (Tanabe et al. 1981). Therefore, heavily chlorinated congeners are preferentially retained,
probably due to a lower metabolic rate. Elimination half-lives from blood between 4.1 and 24.1
months were reported for 2,3',4,4',5-pentachlorobiphenyl in people who had consumed PCB
contaminated rice. The elimination half life for 2,3,3',4,4'-pentachlorobiphenyl ranged from 3.3 to
12.4 months (ATSDR 1995). Larger amounts of PCBs are transferred to infants through mother's
milk than through placental transfer (ATSDR, 1995). A Canadian study estimated that after the first
14 days of breast-feeding, infants had ingested 144 g of PCBs, and their PCB body burden was
0.32 ppm (Mes et al., 1984).
3. NONCARCINOGENIC HEALTH EFFECTS
3.1 ORAL EXPOSURES
3.1.1 Acute Toxicity
3.1.1.1 Human
PCBs are slowly metabolized compounds. Therefore, toxic symptoms usually occur after long-term exposure and bioaccumulation (USAF 1989). No specific data concerning effects of acute
exposure to Aroclor® 1254 in humans were located in the available literature. Effects from acute
exposure to PCBs (which may be manifested weeks to months after exposure) may include facial
edema, ocular discharge, swollen eyelids, conjunctival hyperemia, visual and hearing disturbances,
decreases in diastolic and systolic blood pressure, weakness and numbness of the extremities,
neurobehavioral and psychomotor impairment, GI upset, diarrhea, hepatitis, chloracne, and
asymptomatic hyperthyroxinemia (HSDB 1995).
3.1.1.2 Animal
In most species, the initial sign of acute PCB intoxication is weight loss or decreased weight
gain. Severely intoxicated rats have shown ataxia, diarrhea, and lack of response to pain stimuli.
Histopathological effects are observed mainly in the liver and kidney. The median time to death is
2 to 3 weeks for small laboratory animals (USAF 1989).
Oral LD50 values for Aroclor® 1254 are 1010 and 1295 mg/kg/day in male Osborne-Mendel and
Sherman rats, respectively, and 4000 mg/kg/day in the mink (ATSDR 1995). Rats administered
1.0 mg/kg/day Aroclor® 1254 in the diet for 4 days exhibited increased relative liver weight and
increased serum cholesterol (Carter 1984,1985). Increased serum cholesterol levels were also
observed in rats administered 1.9 mg/kg/day Aroclor® 1254 in the diet for 2 weeks (Carter and Koo
1984). Hepatic vacuolar degeneration and a 30% decrease in body weight gain were observed in rats
administered 50 mg/kg/day Aroclor® 1254 in the diet for 14 days. In rats administered Aroclor® 1254
(7.5 mg/kg/day) in the diet for 7 days, increased relative liver weight, decreased liver glucose 6-phosphatase activity, and decreased serum T4 hormone were observed (Price et al. 1988). In mice
administered 130 mg/kg/day Aroclor® 1254 in the diet for 2 weeks, a 10-fold increase in serum
corticosterone and a 2-fold increase in relative adrenal weight were observed. (Sanders et al. 1974).
In rats treated with a single gavage dose of 500 mg/kg Aroclor® 1254, decreased dopamine levels
were observed in the caudate nucleus (Seegal et al. 1986).
3.1.2 Subchronic Toxicity
3.1.2.1 Human
Information on the subchronic oral toxicity of Aroclor® 1254 in humans was not available.
3.1.2.2 Animal
Byrne et al. (1987) fed female Sprague-Dawley rats 0, 1, 5, 10, or 50 ppm Aroclor® 1254 in the
diet for 5 to 7 months. A dose-dependent decrease in serum T3 and T4 levels was observed,
primarily as a result of direct damage to the thyroid. Decreased adrenal weights and decreased
circulating adrenal cortex hormones were also observed. In another study, Street and Sharma (1975)
fed groups of female New Zealand white rabbits 0, 0.18, 0.92, 2.10, or 6.54 mg/kg/day Aroclor®
1254 in the diet for 8 weeks. After 4 weeks, the rabbits were immunized with injected sheep red
blood cells (SRBC). SRBC-induced increases in serum gamma-globulin were consistently decreased
by exposure, but this decrease was not statistically significant. The number of globulin-producing
cells in popliteal lymph nodes was significantly decreased at 0.92 and 6.54 mg/kg/day. Skin
sensitivity to tuberculin was lower in the treated groups. Histologic atrophy of the thymus cortex was
observed in all treatment groups except at 0.92 mg/kg/day. Relative liver and spleen weights were
significantly increased at the two highest doses; liver weight was increased 74% at the high dose.
In another study, 5 mg/kg body weight Aroclor® 1254 was orally administered in a 45 ml aliquot of
0.25% gelatin in apple juice 3 times per week to monkeys until the animals were moribund--69 to
122 days (Iverson et al. 1982). The monkeys exhibited labored breathing, ataxia, and tremors, and
a 3-methyl cholanthrene type of mixed function oxidase induction was observed in the liver.
An accidental case of Aroclor® 1254 poisoning occurred in a group of monkeys (Geistfeld et
al. 1982). Six weeks after being transferred to a new primate facility, 53/249 monkeys died of
gastropathy characterized by mucinous gastric hyperplasia. All affected monkeys exhibited the
following clinical signs: diarrhea, weakness, gingivitis, emaciation, dehydration, alopecia, and
conjunctivitis. An additional 32 monkeys exhibited these clinical signs before death, but no gastric
hyperplasia was observed at autopsy. Anorexia and respiratory distress frequently occurred, and
when gastric hyperplasia occurred, it usually lasted 4 to 8 weeks and did not respond to treatment.
Microscopic examination revealed glandular hyperplasia and cysts. Tissue analysis revealed
Aroclor® 1254 in the liver and adipose tissue at levels up to 14 ppm. Paint and concrete samples
taken from the monkey house contained 25 ppm Aroclor® 1254. When the surviving animals were
removed from the facility, they began to recover.
3.1.3 Chronic Toxicity
3.1.3.1 Human
Specific information on the chronic oral toxicity of Aroclor® 1254 to humans was not available.
However, information from accidental poisonings that occurred in Japan and Taiwan (Yusho and
Yu-Cheng incidents) and from occupational exposure (Section 3.2.3.1) to PCBs is available.
Yusho. The most notable example of the possible effects of PCB exposure in humans is the
Yusho incident which occurred in Japan in 1968. Kaneclor® 400 (48% Cl) inadvertently leached
into a commercial rice oil preparation. After a latent period of 5 to 6 months, symptoms began to
manifest. It was initially estimated that the oil was contaminated with 1000 to 3000 ppm PCBs but
reanalysis revealed the presence of 968 ppm PCBs and 8 ppm polychlorodibenzofurans (PCDFs).
The majority of people consumed about 200 g/kg/day. Early symptoms of Yusho (literally "oil
disease") included enlargement and hypersecretion of the Meibomian gland of the eye, swelling of
the eyelids, pigmentation of the fingernails and mucous membranes, fatigue, and nausea. These
symptoms were followed by hyperkeratosis, darkening of the skin with follicular enlargement,
acneform eruptions with secondary staphylococcal infection, edema of the arms and legs, and
bronchitis-like respiratory symptoms which persisted for years (Masuda and Yoshimura 1984).
As dermal and mucosal conditions improved after a few years post-exposure, evidence of
various systemic disturbances became apparent. Most victims displayed neurological symptoms
(e.g., headache, numbness in the limbs, hypesthesia, and neuralgic limbs). Central nervous system
damage was not apparent. A significant positive correlation was noted between PCB blood levels
in Yusho victims and the severity of dermal lesions, ocular symptoms, elevated serum triglyceride
concentrations, limb paresthesia, and other symptoms (EPA 1980).
The majority of Yusho victims complained of persistent cough, sputum production, and chronic
bronchitis-like symptoms. Secondary respiratory infections were often noted, although no fever and
little change in leucocyte count or erythrocyte sedimentation rate was seen (Shigematsu et al. 1978).
Examination of 400 Yusho patients revealed respiratory symptoms including expectoration in 40%
and wheezing in 2% of 289 non-smokers; the former (along with persistent coughing) appeared with
the development of skin eruptions, while the latter appeared several months later. Other respiratory
symptoms included bronchiolitis in many, and pneumonia or atelectasis in about 10% of the patients.
The incidence and severity of the respiratory symptoms correlated well with the concentration of
PCB in the blood and sputa. Viral or bacterial infection increased the severity of the respiratory
symptoms and persisted in patients with blood PCB levels over 10 ppb.
Examination of organs of deceased Yusho victims revealed high levels of PCDFs. Liver and
adipose tissue samples of Yusho patients revealed 2 to 25 and 6 to 13 ppb PCDFs, respectively,
while no PCDFs were detected in unexposed volunteers. PCDFs were also shown to be retained in
the body, particularly in the liver, much longer than PCBs. In fact, 2, 3, 4, 7, 8-penta-CDF was still
present in the tissue of a patient 9 years after the poisoning incident (Masuda and Yoshimura 1984).
Yu-Cheng. An incident similar to Yusho was reported in Taiwan in 1979 following
consumption of rice oil contaminated with PCBs. The resulting disease was called Yu-Cheng (oil
disease). Symptoms included acneform eruptions and follicular accentuation, pigmentation of the
skin and nails, swelling of the eyelids and eye discharge, headache, nausea, and numbness of the
limbs. Blood disorders included a decrease in red blood cells, an increase in white blood cells, and
a decrease in hemoglobin and gamma-immunoglobin (EPA 1980).
Chang et al. (1981) measured B-cells to evaluate effects on humoral immunity and T-cells to
test for effects on cell-mediated immunity in Yu-Cheng patients. Thirty patients with an average
blood PCB level of 45 ppb were studied. PCB poisoning did not affect the total lymphocyte count
or the number of B-cells. Suppressor T-cells were not affected, but helper T-cells were significantly
decreased in Yu-Cheng patients (26.1% vs. 36.9% helper T-cells in control subjects) indicating a
range in sensitivity of different lymphocytes to PCBs. Chang et al. concluded that cell-mediated
immunity, as shown by decreased T-cell levels, was significantly correlated with PCB toxicity.
Chen et al. (1985) found that the severity of neuropathy was related to the concentration of PCB
and PCB derivatives in the blood. The average blood level of PCB in 110 Yu-Cheng victims was 39
ppb. Sensory and motor nerve conduction velocities were shown to be significantly slower in
PCB-intoxicated patients.
3.1.3.2 Animal
Groups of 16 adult (11.1 +/-4.1 years at study initiation) female rhesus monkeys ingested
gelatin capsules containing 0, 0.005, 0.02, 0.04, or 0.08 mg/kg/day Aroclor® 1254 daily for more
than 5 years. Results of general health and clinical pathology evaluations during the first 37 months
of the study were reported by Arnold et al. (1993 a,b). Results of reproductive endocrinology
evaluations after 24 or 29 months were reported by Truelove et al. (1990) and Arnold et al. (1993a).
Results of immunological studies are reported in Tryphonas et al. (1989, 1991 a,b). Statistically
significant (p0.05) increases in the incidence of inflamed and/or prominent Meibomian glands
compared to controls were observed at 0.005, 0.02, and 0.08 mg/kg/day. Significant (p0.05) dose-related trends were observed for increased total incidence of inflamed and/or prominent Meibomian
glands, decreased onset time of inflamed and/or prominent Meibomian glands, and increased
incidences of ocular exudate. Statistically (p0.05) significant incidences of changes in finger and/or
toe nails were also observed. Nail folding and separation were observed at 0.005, 0.04, and 0.08
mg/kg/day and elevated nails and prominent beds were increased at 0.08 mg/kg/day. Decreased
onset time of nail changes exhibited a dose-related trend (p0.05). Significant (p0.05 or 0.01)
decreases in IgG antibody levels were observed at all dose levels, and significant (p0.05 or 0.01)
decreases in IgM levels were observed in all treatment groups except 0.02 mg/kg/day in response
to injected SRBC after 23 months of exposure. At 0.08 mg/kg/day, a significant (p0.05) decrease
in the percent of helper T-lymphocytes, significant (p0.05) increase in suppressor T-lymphocyte
count, and significant (p0.01) decrease in helper/suppressor ratio were observed after 23 months
of exposure. After 55 months of exposure, there was a significant dose-related decrease (p<0.0005)
in the IgM antibody response to SRBC in all treatment groups. IgG antibody response to SRBC was
significantly (p<0.01) decreased only at 0.04 mg/kg/day, although the overall trend was significant
(p=0.033). Significant (p<0.05) decreases in average serum cholesterol values were observed at 0.04
mg/kg/day and significant (p<0.05) decreases in reticulocyte count, serum cholesterol, total
bilirubin, and alpha-1+ alpha-2-globulins were observed at 0.08 mg/kg/day. Significant (p<0.05)
dose-related decreasing trends were observed for reticulocyte count, cholesterol, and total bilirubin.
Dose-related decreasing linear trends were observed for erythrocyte count, mean platelet volume,
hematocrit, and hemoglobin concentration. No statistically significant changes were observed for
any thyroid endpoint or for menstrual effects.
Hepatotoxicity is a prominent effect of Aroclor® 1254 that has been well characterized (EPA
1995a). Effects include hepatic microsomal enzyme induction, increased serum levels of liver-related enzymes indicative of hepatocellular damage, liver enlargement, lipid deposition, fibrosis,
and necrosis. In rats, subchronic doses of 1.25 to 2.5 mg/kg/day have been reported to induce
increased liver weight and hepatic biochemical changes; however, the lowest doses producing
hepatic effects are generally higher than the doses that induce thyroid, adrenal, and bone effects
(Litterset et al. 1972, Bruckner et al. 1974, Kling and Gamble 1982, Andrews 1989). Rats fed 6.8
mg/kg/day Aroclor® 1254 in the diet for 8 months (Kimbrough et al. 1972) or 50 mg/kg/day for 30
days (Kling et al. 1978) developed fatty and necrotic livers.
3.1.4 Developmental and Reproductive Toxicity
3.1.4.1 Human
The ability of PCBs to cross the placenta and affect the fetus was evident in babies born to
Yusho (Section 3.1.3.1) mothers. Of the 12 infants born in 1968 to 11 Yusho mothers and 2
non-Yusho women with Yusho husbands, 10 infants lived and 2 were stillborn. All infants had eye
discharge. Nine of the ten live infants had dark grayish skin, and five had grayish pigmentation of
the gums and nails. One of the stillborn fetuses had marked hyperkeratosis, atrophy of the epidermis,
and cystic dilation of the hair follicles. In addition, an increase in melanin pigment was present in
the blood cells and the epidermis. All newborns were small, and the growth rate of the 10 infants
was significantly slower than unaffected children. Teeth were erupted at birth and there was spotted
calcification of the parieto-occipital skull, wide fontanelles, and sagittal suture along with facial
edema and exophthalmic eyes (Yamashita 1977).
Miller (1985) also reviewed the effects of PCBs on infants of exposed mothers. A deep brown
pigmentation of the skin (usually referred to as cola-colored skin) was the most prevalent symptom.
Biopsy of the skin showed an increase in melanin and hyperkeratosis. The pigmentation cleared up
within 2 to 5 months. Low birth weights were also a primary effect of PCB toxicity. The majority
of infants had a thick white discharge from the eye and cysts of the Meibomian gland. Some of the
children exhibited severely swollen eyelids and facial edema. Gingival hyperplasia and teeth present
at birth occurred in 16% of the infants investigated. The children with gum overgrowth and natal
teeth eruption also had spotty calcification in the occipital region of the skull and a wide separation
of the sagittal suture and large anterior and posterior fontanelles (membrane covering the unossified
space in the skull). These symptoms suggest an irregular calcification which may explain the large
unossified areas of the brain and the reduced resistance of the mandible to erupting teeth.
Taylor et al. (1984) examined personnel records from PCB manufacturing facilities engaged
in producing capacitors using Aroclor® 1016, Aroclor® 1254, and Aroclor® 1242. A total of 388
pregnancies were reported for 354 females and 51 births were reported for 39 females who worked
directly with PCB manufacturing. High exposure to PCBs was associated with reduced birth weight
even after adjustment for year of birth, maternal parity, and sex of infant. Mean gestation age was
reduced by 6.6 days after adjustment for these same variables. After adjusting for gestational age,
the average birth weight in the high exposure group was reduced by 58 grams.
3.1.4.2 Animal
Numerous publications have demonstrated the ability of PCBs to cross the placenta and
accumulate in fetal tissues. However, indications of structural malformations, genetic changes, or
other teratogenic effects have been few; most oral exposure studies have reported negative results.
Reproductive capacity can be notably depressed with PCB exposure, particularly in females (USAF
1989).
Severe reproductive failure occurred in female minks following oral administration of 1, 5, or
10 ppm of Aroclor® 1254 for 4 months. The rates of conception were 8/10, 3/12, and 0/6,
respectively, compared to 11/11 in controls. Decreased fetal survival was also evident; the
incidences of live births were 3/9 (33%), 33/43 (77%), and 56/66 (85%) for the 5 ppm, 1 ppm, and
control groups, respectively (Ringer et al. 1972, Aulerich et al. 1971).
Aulerich et al. (1985) observed similar reproductive failure in female minks fed 2.5 ppm of
Aroclor® 1254 for one month prior to mating and through parturition. Only 1/10 treated females
whelped a kit, and it was stillborn.
Truelove (1982) investigated the teratogenic and embryotoxic effects of ingested Aroclor® 1254
on cynomolgus monkeys. Beginning on day 60 of gestation, two pregnant monkeys were given 100
g/kg/day, one monkey was given 400 g/kg/day, and one monkey served as a control. Treatments
were administered daily throughout gestation and post-partum. Offspring of both monkeys fed 100
g/kg Aroclor® 1254 were delivered stillborn. The 400 g/kg treated monkey delivered a live
offspring, but both the birth weight and the weight gain for the next 130 days were significantly
reduced. The offspring died on day 139 due to impaired immunological function; autopsy revealed
acute bronchopneumonia. The only clinical sign of maternal toxicity was the loss of fingernails in
one of the 100 g/kg treated monkeys and the 400 g/kg treated monkey. All treated adult monkeys
also showed signs of diminished immunologic capacity on day 50 post-partum (148 days of
treatment). At autopsy, the PCB concentrations of the liver and kidney in the 400 g/kg treated dam
were 7.17 ppm and 1.88 ppm, respectively. The nursing infant of this dam had a liver PCB
concentration of 47.94 ppm and a kidney concentration of 23.72 ppm. PCB content in the adipose
tissue of the exposed infant increased from 35 ppm at 5 days of age to 483 ppm on day 139 when
the infant died. These high accumulations of PCBs in the infant resulted from the transfer of PCBs
from the mother to the infant via the milk.
Spencer (1982) fed female albino rats 0, 25, 50, 100, 200, 300, 600 or 900 ppm Aroclor® 1254
daily on days 6 through 15 of gestation. No embryonic resorption was observed by day 12 in females
fed up to 900 ppm Aroclor® 1254. Maternal toxicity was seen at 600 and 900 ppm levels. Fetotoxic
effects were present in the form of decreased fetal survival rates at levels of 300 ppm and above and
reduced birth weight at 100 ppm or more.
Male and female Wistar rats were given drinking water containing 70 ppm Aroclor® 1254 for
9 weeks. After the first week of treatment, treated rats were allowed to mate with control rats. No
adverse effects on the fertility of male rats exposed to Aroclor® 1254 were noted. Several treated
females died during the 7th week and by the 9th week, fetal resorption was obvious. By the end of
the 9th week, both the treated males and females were returned to ordinary tap water. Biochemical
studies revealed that Aroclor® 1254 elevated the mixed function oxidase activity. This increase
persisted even after exposure to Aroclor® 1254 was terminated and rats were given tap water (Baker
et al. 1977).
Overmann et al. (1987) exposed female rats from mating to weaning of pups to 2.5, 26, or 269
ppm of Aroclor® 1254 in their diet. The high dose decreased the number of litters and lowered
average pup birth weight. Most of the pups in this group died during the first 8 days after birth. The
only toxic effects observed in the 2.5 or 26 ppm groups were reduced pup growth and delays in some
neurobehavioral assessments. These delays occurred in a dose-related manner. No physical
deformities, reduction in litter size, increase in dead pups, or change in sex ratio was observed in any
treatment group.
PCBs have the ability to induce the liver mixed function oxidase system which results in a
faster than normal rate of metabolism of endogenous substrates such as steroid hormones. The
decrease in steroid hormones is expected to affect reproduction. To investigate this effect, Brezner
et al. (1984) orally administered 0 or 10 mg/kg Aroclor® 1254 daily for at least 30 days to female
Wistar rats that had just delivered litters. The only PCB exposure to the pups was via the mother's
milk. Over the 4-week dosing period, maternal rats experienced a significant weight loss. Rats
exposed for 6 weeks exhibited a significantly prolonged estrous cycle (67.3% of the treated rats were
affected vs. 6% in control rats). Receptivity of females was decreased in the treated rats; i.e., sperm
were present in the vaginal smears of only 79.5% of the treated females vs. 100% in the control
females.
Among pregnant females, 89% of the treated females completed pregnancy vs. 100% of control
females. Vaginal bleeding occurred in 71% of treated females on days 10 to 15 of gestation and 71%
of the treated females delivered 1 to 3 days late while only 21% of controls showed vaginal bleeding
and 10% delivered late. The average litter size of PCB-treated rats was smaller than normal (6.5 vs.
10 pups in the control group) and an average of 1.5 pups/litter were dead in the treated group.
Development of the pups from treated dams was slower, and an increase in mortality was seen
before weaning. In female offspring of the Aroclor® 1254-treated group, vaginal opening occurred
at an earlier age (39 days vs. 43 days in control animals) and there was a significant delay in the
appearance of first estrus (8 days vs. 4.4 days in the control animals). Other reproductive parameters
were not affected. Once PCB exposure ceased, body weight reached control values within 2 to 3
months, and a reversal of the adverse reproductive effects was seen.
Sager and Girard (1983) expanded the findings of Brezner et al. (1984) and reported the results
of early postnatal exposure of rats to Aroclor® 1254 on reproductive performance later in life.
Mothers of the test group were fed 0, 8, 32, or 65 mg/kg Aroclor® 1254 on days 1, 3, 5, 7, and 9 of
lactation. Offspring were then allowed to mature to either young or mature adults. Vaginal opening
and first estrus were delayed in offspring exposed to PCBs. In the mature adult group, the incidence
of pseudopregnancy in animals exposed to 32 mg/kg early in life was markedly increased. In the
high dose group, implantation was significantly inhibited. Additionally, mature adults in the 32 or
65 mg/kg exposure groups exhibited increased embryonic deaths. Sager and Girard concluded that
rats exposed to PCBs early in life through mother's milk experienced reproductive dysfunction in
adult life despite decreasing PCB levels in the body tissue.
Sager (1983) studied the early postnatal effect of PCBs on adult male reproduction in Holtzman
rats. Lactating dams were orally administered 0, 8, 32, or 64 mg/kg Aroclor® 1254 on days 1, 2, 3,
5, 7, and 9. Males were weaned on day 23, allowed to mate beginning on day 130 and autopsied on
day 165. Any pregnant females resulting from the mating period were autopsied on days 11 to 12
of gestation. Examination of the pregnant females revealed a decreased number of implantations and
significantly fewer surviving fetuses. The resorption rate was significantly increased, and
significantly fewer females became pregnant after exposure to the treated males. Treated males
showed a reluctance to mate. Prostate weight was significantly lower in treated male offspring.
Seminal vesicle weight was also decreased in males exposed to the top two dosages while testes
weight was significantly increased.
In a multi-generation study in white-footed mice, Linzey (1988) observed that diets containing
10 ppm Aroclor® 1254 resulted in reduced weight in the offsprings (F1 and F2) and poor reproductive
success in the second (F1) generation.
3.1.5 Reference Dose
3.1.5.1 Subchronic
ORAL RfD: 5E-5 mg/kg/day (EPA 1995b)
NOAEL: None
LOAEL: 0.005 mg/kg/day
UNCERTAINTY FACTOR: 100
PRINCIPAL STUDIES: Arnold et al. 1993a,b; Tryphonas et al. 1989, 1991a,b
COMMENTS: The chronic oral RfD was modified (by removing an uncertainty factor of
3 used to extrapolate from subchronic to chronic exposure) to estimate the subchronic oral
RfD (EPA 1995b).
3.1.5.2 Chronic
ORAL RfD: 2E-5 mg/kg/day (EPA 1995a)
NOAEL: None
LOAEL: 0.005 mg/kg/day
UNCERTAINTY FACTOR: 300
CONFIDENCE:
Study: Medium
Data Base: Medium
RfD: Medium
VERIFICATION DATE: 2/16/94
PRINCIPAL STUDIES: Arnold et al., 1993a,b; Tryphonas et al. 1989, 1991a,b
COMMENTS: The RfD is based on the results of a 5+-year chronic oral study in
female monkeys. The critical effects were ocular exudate, inflamed and prominent
Meibomian glands, distorted finger and toe nails, and decreased antibody (IgG and
IgM) response to sheep red blood cells. An uncertainty factor of 10 was used to
account for sensitive individuals. An additional factor of 3 was used for extrapolation
from rhesus monkeys to humans. A full factor of 10 was not considered necessary
because of the similarities in toxic responses and metabolism of PCBs between
monkeys and humans and the general physiologic similarities between these species.
A partial factor was applied for the use of a minimal LOAEL since the changes in
ocular tissues and nails were not considered markedly severe. A factor of 3 was
applied to extrapolate to chronic exposure. The full factor of 10 was not considered
necessary since the critical study spanned approximately 25% of the monkey lifespan
and immunological and clinical changes were not duration-dependent (EPA 1995a).
3.2 INHALATION EXPOSURES
3.2.1 Acute Toxicity
3.2.1.1 Human
No specific data concerning acute inhalation exposure to Aroclor® 1254 by the human were
available. Signs and symptoms of short-term human exposure may include anorexia, nausea, edema
of the face and hands, abdominal pain, ocular discharge, and a burning sensation to the skin and eyes
(USAF 1989).
3.2.1.2 Animal
No data concerning acute inhalation exposure of Aroclor® 1254 to animals were available.
3.2.2 Subchronic Toxicity
3.2.2.1 Human
Mild to moderate chloracne was observed in 7 of 14 workers exposed to 0.1 mg/m3 of an
unspecified Aroclor® mixture for an average of 14.3 months (Meigs et al. 1954). The chloracne was
primarily found on the face, especially the cheeks, forehead, and ears. In another study, three cases
of chloracne were reported among an unspecified number of autoclave operators exposed to 5.2 to
6.8 mg/m3 Aroclor® 1254 in 1954 (Bertazzi et al. 1987). Pyrolytic formation of chlorinated
dibenzofurans CDFs was a confounding factor in both studies.
3.2.2.2 Animal
Groups of animals (1 cat, 6 guinea pigs, 10 mice, 4 rabbits, and 10 rats/group) were exposed
to 5.4 mg/m3 Aroclor® 1254 for 7 hours/day, 5 days/week over 121 days, or 1.5 mg/m3 Aroclor®
1254 for 7 hours/day, 5 days/week over 213 days (Treon et al. 1956). Effects observed at 1.5 mg/m3
and 5.4 mg/m3 included unspecified, moderately severe hepatic degeneration and slight renal tubule
degeneration in the cat; unspecified, slight hepatic degeneration in mice; fatty alterations and
hydropic degeneration of the liver in rabbits; and slight hepatic vacuolation and a decrease in body
weight gain (22% at 1.5 mg/m3 and 16% at 5.4 mg/m3) in guinea pigs.
3.2.3 Chronic Toxicity
3.2.3.1 Human
The relative contribution of the inhalation and dermal routes in occupational exposures is
unknown; however, the data will be primarily presented in the inhalation section of this document.
Occupational exposure to PCBs presents a different clinical picture than oral exposure from
accidental poisoning. The symptoms most commonly observed appear to be dermal and mucosal
effects but no consistent disturbances in liver function. An investigation of former capacitor workers
was presented by Lawton et al. (1985). Exposure to PCBs occurred between 1954-1977 when
Aroclor® 1242 and 1016 were used extensively. Air levels were estimated to be at least 690 g/m3.
Dermal contact also occurred. An 80% clearance of the lower chlorinated PCBs was noted in
workers re-examined 29 months after exposure had ceased. Traces of highly chlorinated PCBs were
found in the blood of long-time workers, particularly those exposed to Aroclor® 1254 before its use
was discontinued in 1954. In 1976, blood levels of this compound were 8 ppm. By 1979, 25 years
after exposure was discontinued, blood levels were 6 ppm. There was also a statistically significant
association of log serum triglycerides and total cholesterol with every measure of log serum PCBs.
Smith et al. (1982) investigated cholesterol and triglyceride levels in PCB-exposed workers and
the possible correlation to cardiovascular effects. Two-hundred twenty-eight employees of an
electrical equipment manufacturing plant were evaluated. From 1959 to 1971, Aroclor® 1242 was
used; Aroclor® 1016 was used thereafter. Forty-seven employees from a public utility plant were
also evaluated, 14 of which worked in transformer maintenance. Another 46 employees of a private
utility company, 15 working in transformer maintenance and 10 who worked in transformer
overhaul, were included. Serum log PCBs correlated significantly with symptoms of mucous
membrane and skin irritation, of systemic malaise, and of altered peripheral sensation. Serum log
PCBs were also correlated with serum (SGOT), plasma log (triglycerides), and log high density
lipoprotein, which indicate an effect on liver metabolism and possible development of
cardiovascular disease.
3.2.3.2 Animal
Information on the chronic inhalation toxicity of Aroclor® 1254 or PCBs to animals was not
available.
3.2.4 Developmental and Reproductive Toxicity
3.2.4.1 Human
Fifty-one infants born to 39 mothers employed at two capacitor manufacturing plants who had
a history of direct exposure to Aroclors® 1254, 1242, and/or 1016 had lower mean birth weights and
shorter mean gestational ages than those of 337 infants born to 280 women who worked in low-exposure areas (Taylor et al. 1984). The low-exposure infants were heavier than matched community
controls, thereby establishing no dose-response. The study results suggest that the decreased birth
weights of the high-exposure infants may have been due to shortened gestational periods rather than
decreased interuterine growth and that the decreased birth weights may have been partially mediated
by high exposure to PCBs.
3.2.4.2 Animal
No data concerning developmental or reproductive effects from inhalation exposure of animals
to Aroclor® 1254 or PCBs were available.
3.2.5 Reference Concentration
3.2.5.1 Subchronic
No subchronic reference concentration (RfC) for Aroclor® was available.
3.2.5.2 Chronic
No chronic RfC for Aroclor® was verified.
3.3 OTHER ROUTES OF EXPOSURE
3.3.1 Acute Toxicity
3.3.1.1 Human
Information on the acute toxicity of Aroclor® 1254 or other PCBs to humans by other routes
of exposure was not available.
3.3.1.2 Animal
A single dermal dose of 2000 mg/kg Aroclor® 1254 was fatal to hairless mice within 24 hours
of application (ATSDR 1995). It was not specified whether all three treated mice died. The identity
of the administration vehicle was not specified.
3.3.2 Subchronic Toxicity
3.3.2.1 Human
Information on the subchronic toxicity of Aroclor® 1254 or other PCBs to humans by other
routes of exposure was not available.
3.3.2.2 Animal
Skin appearance and histology were normal in three hairless mice that were dermally treated
with Aroclor® 1254 in estimated doses of < 100 mg/kg/day on 4 days/week for 6 weeks (Puhvel et
al. 1982).
3.3.3 Chronic Toxicity
3.3.3.1 Human
The relative contribution of the inhalation and dermal routes in occupational exposures is
unknown; however, these data were primarily presented in the inhalation section of this document
(Section 3.2.3.1.). A study of capacitor workers showed PCB-exposure measurements ranging from
48 to 275 g/m3 in workroom air and 2 to 28 g/cm2 for Pyralene® 3010 or Apirolio® on the skin of
the palms (Maroni et al. 1981a, b). Of 80 exposed workers, 16 exhibited evidence of liver
involvement including asymptomatic hepatomegaly and/or elevated serum SGTP, SGOT, or SGPT.
No control group was included in this study.
3.3.3.2 Animal
Information on the chronic toxicity of Aroclor® 1254 or other PCBs to animals by other routes
of exposure was not available.
3.3.4 Developmental and Reproductive Toxicity
Information on the developmental and reproductive toxicity of Aroclor® 1254 or other PCBs
to humans or animals by other routes of exposure was not available.
3.4 TARGET ORGANS/CRITICAL EFFECTS
3.4.1 Oral Exposures
3.4.1.1 Primary target organs
Liver: Hepatotoxicity is a well-characterized effect of Aroclor® 1254 and other PCBs. The
spectrum of effects include hepatic microsomal enzyme induction, increased serum levels
of liver-associated enzymes suggestive of possible liver damage, liver enlargement, lipid
deposition, fibrosis and necrosis. Subchronic doses of 1.25 to 2.5 mg/kg/day have been
reported to produce increased liver weight and hepatic biochemical changes in rats.
Skin: Chloracne has been observed in humans and several animal species following PCB
exposure. Distorted growth of finger and toe nails has been observed in monkeys.
3.4.1.2 Other target organs
Immune function disorders and decreased reproductive capacity, including low-birth weight
and decreased gestational time, have been described in human and other animal species. Ocular
discharge and swollen Meibomian glands have been described in humans and monkeys. Thyroid and
kidney damage has also been observed.
3.4.2 Inhalation Exposures
3.4.2.1 Primary target organs
1. Skin: Mild to moderate chloracne was observed in occupationally exposed individuals.
Liver: Liver toxicity similar to that observed from oral exposure to PCBs is also seen with
inhalation exposure. However, comparatively high levels (compared to oral equivalents)
were required to produce these effects by the inhalation route.
3.4.2.2 Other target organs
Lower mean birth weights and shorter mean gestational ages in infants born to occupationally-exposed mothers may have been mediated by PCB exposure.
3.4.3 Other Routes of Exposure
3.4.3.1 Primary target organs
1. Liver: Occupationally-exposed individuals exhibited asymptomatic hepatomegaly and
elevated serum levels of liver-associated enzymes, perhaps due to a dermal contribution.
2. Skin: Chloracne has been observed in occupationally-exposed individuals. The relative
contributions of the inhalation and dermal routes are not precisely known.
4. CARCINOGENICITY
4.1 ORAL EXPOSURES
4.1.1 Human
Information on the carcinogenicity of Aroclor® 1254 or any Aroclor® PCB formulation to
humans following oral exposure was not available. There is inconclusive evidence of liver cancer
in people who were exposed to heated Aroclor ® PCBs during the Yusho and Yu-Ching incidents;
however, chlorinated dibenzofurans were major contaminants (ATSDR 1995).
4.1.2 Animal
Aroclor® 1254. Kimbrough and Linder (1974) fed 300 ppm Aroclor® 1254 to male BALB/cJ
mice for 11 months or for 6 months followed by the control diet for the remaining 5 months of the
study. In the mice fed Aroclor® 1254 for 11 months, hepatomas were observed in 9/22 (41%)
survivors and adenofibrosis and enlarged livers in all 22 survivors. Examination of livers of mice
treated for 6 months and then allowed to recover for 5 months showed slight-to-moderate diffuse,
interstitial fibrosis. One mouse developed a small hepatoma. No hepatic lesions were observed in
58 control mice.
In a study conducted by the National Cancer Institute (NCI 1978, Ward 1985) male and female
F344 rats were administered 0, 25, 50 or 100 ppm Aroclor® 1254 daily for 104 to 105 weeks.
Clinical signs of toxicity including alopecia, amber-colored urine, facial edema, exophthalmos and
cyanosis were observed in the 50 or 100 ppm Aroclor® 1254 groups. An increased incidence of
lymphoma and leukemia combined was seen in males (12.5% for control animals, 8.3% for the low
dose animals, 20.8% for the 50 ppm group and 37.5% for the high dose group). However,
comparisons of each treatment group with the matched controls were not statistically significant and
the tumors could not clearly be related to Aroclor® 1254 treatment. Hepatocellular adenomas and
carcinomas were found in Aroclor® 1254-treated animals but not in control animals. Furthermore,
a dose-related incidence of nodular hyperplasia appeared in all animals treated with Aroclor® 1254
but this trend was not statistically significant. Adenocarcinomas of the stomach, jejunum, or cecum
were observed in two treated male and two treated female rats as well as a carcinoma in a treated
male. These lesions, although not statistically significant, appear to be treatment-related since no
control animals developed these types of tumors. NCI concluded that Aroclor® 1254 was not
carcinogenic in F344 rats but that the high incidence of hepatocellular proliferative lesions in both
male and female rats was Aroclor® 1254-related. Additionally, the tumors found in the
gastrointestinal tract may also have been due to Aroclor® 1254 administration.
Morgan et al. (1981) limited their investigation to the gastric effects of PCBs. Male and female
F344 rats were fed a diet containing 0, 25, 50 or 100 ppm Aroclor® 1254 for 26 months. Rats fed 50
or 100 ppm Aroclor® 1254 had a lower body weight than the control animals and developed signs
of PCB toxicity. The incidence of stomach lesions increased as the dietary intake of Aroclor® 1254
increased. In control animals, 6.4% developed lesions while in the 25, 50, and 100 ppm PCB-treated
groups, 10.4%, 16.7%, and 35.4% developed lesions, respectively. A total of six definite and two
suspected, but not confirmed, adenocarcinomas developed in Aroclor® 1254-fed rats. Stomach
adenocarcinomas rarely occur in F344 rats. Morgan et al. concluded that Aroclor® 1254 incorporated
into the diet for 2 years induced intestinal metaplasia which resulted in the probable induction of
adenocarcinomas in F344 rats.
Hendricks et al. (1977) fed rainbow trout for a year on Aroclor® 1254, Aflatoxin B1 or Aroclor®
plus Aflatoxin. No liver tumors were observed in the trout fed Aroclor® alone, and the fish fed
Aroclor® 1254 plus Aflatoxin B1 had less liver tumors than fish fed Aflatoxin B1 alone.
Other PCBs. Norback and Weltman (1985; also Weltman and Norback 1982) fed 70 male and
70 female Sprague-Dawley rats Aroclor® 1260 in the diet at a level of 100 ppm for 16 months,
followed by 50 ppm for 8 months and finally a control diet for 5 months. Hepatocellular tumors
developed in 95% of the female rats and 15% of the male rats. Seventy percent of the females also
developed various forms of bile duct tumors; only 37% of the males developed such tumors.
Norback and Weltman concluded that Aroclor® 1260 was a complete liver carcinogen acting as both
an initiator and promotor.
">
Kimbrough et al. (1975) fed 0 or 100 ppm Aroclor® 1260 to female Sherman rats for 21 to 22
months. Hepatocellular carcinomas developed in 14.13% of the treated rats and in only 0.58% of
control animals. Treated rats also developed a high incidence of neoplastic liver nodules (79.5% vs.
zero in control animals) and hepatocellular alterations (98.9% vs. 16.2% in control rats).
Groups of male Wistar rats were fed a protein diet containing 50 ppm or 100 ppm Aroclor®
1260 for 120 days (Rao and Banerji 1988). Gross hepatic changes, neoplastic nodules, and
adenofibrosis in 75% and 50% of the treated animals, respectively, were observed. The authors were
unable to explain the higher incidence of tumors found in the rats fed the lower concentration of
Aroclor®.
Male Wistar rats were fed a standard diet, a diet supplemented with 100 ppm Clophen A30, or
a diet supplemented with 100 ppm Clophen A60 for 832 days (Schaeffer et al. 1984). Clophen A60
is almost identical in composition to Aroclor® 1260 (IARC 1978), while Clophen A30 appears to
be similar in structure to Aroclor® 1016. Hepatocellular carcinoma was the most frequently found
lesion in animals sacrificed at the end of the experiment, observed in 2, 3, and 61% of the animals
in the control, Clophen A30 and Clophen A60 groups, respectively. Preneoplastic nodules and
neoplastic lesions were found in 50 to 60% of the Clophen A30 animals after day 500, and 100%
of the animals killed after day 800. However, 100% of the Clophen A60 animals had preneoplastic
and neoplastic lesions after day 500. The incidence of preneoplastic nodules and neoplastic lesions
in control animals was low until day 800 after which the incidence rose to 32%.
Ito et al. (1973) fed male DD mice (12/group) with diets containing 100, 250, or 500 ppm
Kannechlors 500, 400, and 300 for 32 weeks. The group fed 500 ppm Kanechlor 500 had a 41.7%
incidence of hepatocellular carcinomas and a 58.3% incidence of nodular hyperplasia. No
hepatocellular carcinomas or nodular hyperplasia was observed in mice fed 100 or 250 ppm
Kanechlor 500 or among those fed any concentration of Kanechlors 400 or 300.
4.2 INHALATION EXPOSURES
4.2.1 Human
A slight increase in the incidence of cancer, particularly melanoma of the skin, has been
reported in a small group of men occupationally exposed to Aroclor® 1254. Eight cancers (in 7
workers) were reported between 1957 and 1975 in 92 workers exposed to Aroclor® 1254. Of these
eight cancers, three were malignant melanoma and two were cancer of the pancreas. Data from the
NCI estimate that 0.04 malignant melanomas should be expected to develop in this group. These
data suggest a possible correlation between Aroclor® 1254 and the development of malignant
melanomas. Exposure to other chemicals was not known (IARC 1978, NIOSH 1975).
An excess risk of cancer of the liver, biliary tract, or gall bladder was found in 2588 workers
(1270 male and 1318 female) from two capacitor factories where PCBs were used. The workers had
been employed at least 3 months between 1940 and 1976. Aroclor® 1254 was used at first, but usage
was later changed to Aroclor®1242 and then to Aroclor®1016. Aroclor® 1254 exposure data were not
available (ATSDR 1995).
4.2.1 Animal
Information on the carcinogenicity of Aroclor® 1254 or any PCB by inhalation exposure to
animals was not available.
4.3 OTHER ROUTES OF EXPOSURE
4.3.1 Human
Information on the carcinogenicity of Aroclor® 1254 or any PCB in humans by other routes of
exposure was not available.
4.3.2 Animal
A single 0.1 mg dose of Aroclor® 1254 showed no initiating activity when applied to the shaved
skin of female CD-1 mice followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA)
two times per week for 32 weeks (DiGiovanni et al. 1977). Aroclor® 1254 was not a tumor promotor
when applied to the shaved skin of female CD-1 mice (0.1 mg/mouse, 2 times/week for 30 weeks)
that were initiated with dimethyl benzanthracene (Berry et al. 1978, 1979) or to female HRS/J
hairless mice (1 mg/mouse, 2 times/week for 20 weeks) that were initiated with N-methyl-N'-nitro-N-nitrosoguanidine (Poland et al. 1983).
4.4 EPA WEIGHT-OF-EVIDENCE
4.4.1 Oral-PCBs
CLASSIFICATION: Group B2, Probable Human Carcinogen (EPA 1995c)
BASIS: There is no EPA Cancer Classification specifically for Aroclor® 1254, based on
hepatocellular carcinomas in three strains of rats and two strains of mice and inadequate
yet suggestive evidence of excess risk of cancer in humans by ingestion and inhalation or
dermal contact (EPA 1995c).
4.4.2 Inhalation
CLASSIFICATION: None
4.5 CARCINOGENICITY SLOPE FACTORS
4.5.1 Oral-PCBs
SLOPE FACTOR: 7.7 (mg/kg/day)-1 (EPA 1995c)
DRINKING WATER UNIT RISK: 2.2E-4 (g/L)-1 (EPA 1995c)
VERIFICATION DATE: 4/22/87
PRINCIPAL STUDIES: Norback and Weltman, 1985
COMMENTS: Values are for Polychlorinated biphenyls. There are no EPA values derived
specifically for Aroclor® 1254, based on an increase in hepatocellular tumors in female
Sprague-Dawley rats treated with Aroclor® 1260 in the diet (EPA 1995c).
4.5.2 Inhalation
No inhalation slope factor or unit risk has been verified.
5. REFERENCES
Andrews, J. E. 1989. Polychlorinated biphenyl (Aroclor® 1254) induced changes in femur
morphometry calcium metabolism and nephrotoxicity. Toxicology. 57:83-96 (cited in EPA
1995a).
Arnold, D. L., Bryce, R., Stapley, R., et al. 1993a. Toxicological consequences of Aroclor® 1254
ingestion by female Rhesus (Macaca mulatta) Monkeys, Part 1A: prebreeding phase-clinical
health findings. Food. Chem. Toxicol. 31:799-810.
Arnold, D. L., Bryce, R., Karpinski, K., et al. 1993b. Toxicological consequences of Aroclor® 1254
ingestion by female Rhesus (Macaca mulatta) Monkeys, Part 1B: prebreeding phase-clinical
and analytical laboratory findings. Food. Chem. Toxicol. 31:811-824.
ATSDR (Agency for Toxic Substances and Disease Registry). 1995. Toxicological Profile for
Polychlorinated Biphenyls. Draft for Public Comment (Update). Prepared by Research Triangle
Institute, under Contract No. 205-93-0606 for ATSDR, Public Health Service, U.S. Department
of Health and Human Services.
Aulerich, R. J., Bursian, S. J., Breslin, W. J., Olson, B. A., and Ringer, R. K. 1985. Toxicological
manifestations of 2,4,5,2',4',5'-, 2,3,6 ,2',3',6'-, and 3,4,5,3',4',5'-hexachlorobiphenyl and
Aroclor® 1254 in mink. J. Toxicol. Environ. Health 15:63-79 (cited in USAF 1989).
Aulerich, R. J., Ringer, R. K., Seagram, H. L., and Yoriatt, W. G. 1971. Effects of feeding coho
salmon and other Great Lakes fish on mink reproduction. Can. J. Zool. 49:611-616 (cited in
USAF 1989).
Baker, F. D., Bush, B., Tumasonis, C. F., and Lo, F. C. 1977. Toxicity and persistence of low-level
PCB in adult Wistar rats, fetuses and young. Arch. Environ. Contam. Toxicol. 5:143-156 (cited
in USAF 1989).
Bergman, A., Klasson-Wheler, E., and Kuroki, H. 1994. Selective retention of hydroxylated PCB
metabolites in blood. Environ. Health Perspect. 102:464-469 (cited in ATSDR 1995).
Berry, D. L., DiGiovanni, J., Juchau, M. R., et al. 1978. Lack of tumor-promoting ability of certain
environmental chemicals in a two-stage mouse skin tumorigenesis assay. Res. Commun. Chem.
Pathol. Pharmacol. 20:101-108 (cited in ATSDR 1995).
Berry, D. L., Slaga, T. J., DiGiovanni, J., et al. 1979. Studies with chlorinated dibenzo-p-dioxins,
polybrominated biphenyls, and polychlorinated biphenyls in a two-stage system of mouse skin
tumorigenesis: Potent anticarcinogenic effects. Ann. NY Acad. Sci. 320:405-414 (cited in
ATSDR 1995).
Bertazzi, P. A., Riboldi, L., Pesatori, A., et al. 1987. Cancer mortality of capacitor manufacturing
workers. Am. J. Ind. Med. 11:165-176 (cited in ATSDR 1995).
Bleavins, M. R., Breslin, W. J., Auerlich, R. J., et al. 1984. Placental and mammary transfer of a
polychlorinated biphenyl mixture (Aroclor® 1254) in the European ferret (Mustela putorius
furo). Environ . Toxicol. Chem. 3: 637-644 (cited in ATSDR 1995).
Brezner, E., Terkel, J., and Perry, A. S. 1984. The effect of Aroclor® 1254 (PCB) on the physiology
of reproduction in the female rat - I. Comp. Biochem. Physiol. 77C:65-70 (cited in USAF
1989).
Bruckner, J. V., Khanna, K. L., and Cornish, H. H. 1974. Effect of prolonged ingestion of
polychlorinated biphenyls on the rat. Food Cosmet. Toxicol. 12:323-330 (cited in EPA 1995a).
Byrne, J. J., Carbone, J. P., and Hanson, E. A. 1987. Hypothyroidism and abnormalities in the
kinetics of thyroid hormone metabolism in rats treated chronically with polychlorinated
biphenyl and polybrominated biphenyl. Endocrinology 121:520-527 (cited in USAF 1989).
Carter, J. R., and Koo, S. I. 1984. Effects of dietary Aroclor® 1254 (PCBs) on serum levels of
lipoprotein cholesterol and tissue distribution of zinc, copper, and calcium in Fischer rats. Nutr.
Rep. Int. 29:223-232 (cited in ATSDR 1995).
Carter, J. W. 1984. Hypercholesterolemia induced by PCBs (Aroclor® 1254) in Fischer rats. Bull.
Environ. Contam. Toxicol. 33:78-83 (cited in ATSDR 1995).
Carter, J. W. 1985. Effects of dietary PCBs (Aroclor® 1254) on serum levels of lipoprotein
cholesterol in Fischer rats. Bull. Environ. Contam. Toxicol. 34:427-431 (cited in ATSDR
1995).
Chang, K. J., Hsieh, K. H., Lee, T. P., Tang, S. Y., and Tung, T. C. 1981. Immunologic evaluation
of patients with polychlorinated biphenyl poisoning: Determination of lymphocyte
subpopulations. Toxicol. Appl. Pharmacol. 61:58-63 (cited in USAF 1989).
Chen, R. C., Tang, S. Y., Miyata, H., Kashimoto, T., Chang, Y. C., Chang, K. J., and Tung, T. C.
1985. Polychlorinated biphenyl poisoning: Correlation of sensory and motor nerve conduction,
neurologic symptoms, and blood levels of polychlorinated biphenyls, quaterphenyls and
dibenzofurans. Environ. Res. 37:340-348 (cited in USAF 1989).
Curley, A., Burse, V. W., Grim, M.E. et al. 1971. Polychlorinated biphenyls: Distribution and
storage in body fluids and tissues of Sherman rats. Environ Res. 4:481-495 (cited in ATSDR
1995).
DiGiovanni, J., Viaje, A., Berry, D. L., et al. 1977. Tumor-initiating ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor® 1254 in the two-stage system of mouse
carcinogenesis. Bull. Environ. Contam. Toxicol. 18:552-557 (cited in ATSDR 1995).
EPA (U.S. Environmental Protection Agency). 1995a. Integrated Risk Information System (IRIS).
Environmental Criteria and Assessment Office, Office of Health and Environmental
Assessment, Cincinnati, OH. Aroclor® 1254 file.
EPA. 1995b. Health Effects Assessment Summary Tables. Annual FY-95. Prepared by the National
Center for Environmental Assessment Cincinnati, OH, for the Office of Emergency and
Remedial Response, Washington, D.C.
EPA. 1995c. Integrated Risk Information System (IRIS). Environmental Criteria and Assessment
Office, Office of Health and Environmental Assessment, Cincinnati, OH. Polychlorinated
biphenyls file.
EPA. 1980. Ambient water quality criteria for polychlorinated biphenyls. EPA Report
No. 440/5-80-068. Washington, D.C.: U.S. Environmental Protection Agency, Office
of Water Regulations and Standards. PB81-117798 (cited in USAF 1989).
EPA. 1977. Code of Federal Regulations. 40 CFR 129.4.
Gage, J. C., and Holm, S. 1976. The influence of molecular structure on the retention and excretion
of polychlorinated biphenyls by the mouse. Toxicol. Appl. Pharmacol. 36:555-560 (cited in
ATSDR 1995).
>
Geistfeld, J. G., Bond, M. G., Bullock, B. C., and Varian, M. C. 1982. Mucinous gastric hyperplasia
in a colony of rhesus monkeys (Macaca mulatta) induced by polychlorinated biphenyl
(Aroclor® 1254). Lab. Anim. Sci. 32:83-86 (cited in USAF 1989).
Hansen, L. G., Welborn, M. E., Borchard, R. E., et al. 1977. Tissue distribution of PCB components
in swine and sheep fed three different rations containing Aroclors 1242 and 1254. Arch.
Environ. Contam. Toxicol. 5: 257-278 (cited in ATSDR 1995).
Hendricks, J. D., Putnam, T. P., Bills, D. D., and Sinnhuber, R. O. 1977. Inhibitory effect of a
polychlorinated biphenyl (Aroclor® 1254) on Aflatoxin B1 carcinogenesis in rainbow trout
(Salmo gairdneri). J. Natl. Cancer Inst. 59:1545-1551 (cited in USAF 1989).
HSDB (Hazardous Substances Data Base). 1995. Aroclor® 1254 file. Retrieved online December 4,
1995.
IARC (International Agency for Research on Cancer). 1978. IARC Monographs on the Evaluation
of Carcinogenic Risks to Humans. Some anti-thyroid and related substances, nitrofurans and
industrial chemicals. Vol. 7. IARC, Lyon, France, pp. 261-289.
Ito, N., Nagasaki, H., Arai, M., et al. 1973. Histopathologic studies on liver tumorigenesis induced
in mice by technical polychlorinated biphenyls and its promoting effect on liver tumors induced
by benzene hexachloride. JNCI. 51:1637-1646 (cited in EPA 1995c).
Iverson, F., Truelove, J., and Hierlihy, S. L. 1982. Hepatic microsomal enzyme induction by
Aroclors 1248 and 1254 in cynomolgus monkeys. Food Chem. Toxicol. 20:307-310.
Kimbrough, R. D., and Linder, R. E. 1974. Induction of adenofibrosis and hepatomas of the liver
in BALB/cJ mice by polychlorinated biphenyls (Aroclor® 1254). JNCI. 53:547-552.
Kimbrough, R. D., Linder, R. E., and Gaines. T. B. 1972. Morphological changes in livers of rats
fed polychlorinated biphenyls. Arch. Environ. Health. 25:354-364 (cited in EPA 1995a).
Kimbrough, R. D., Squire, R. A., Linder, R. E., Strandberg, J. D., Montali, R. J., and Burse, V. W.
1975. Induction of liver tumors in Sherman strain female rats by polychlorinated biphenyl
(Aroclor® 1260). J. Nat. Cancer Instit. 55(6):1453-1456 (cited in USAF 1989).
Kling, D., and Gamble, W.. 1982. Cholesterol biosynthesis in polychlorinated biphenyl-treated rats.
Environ. Res. 27:10-15 (cited in EPA 1995a).
Kling, D., Kunkle, J., Roller, A. S., et al. 1978. Polychlorinated biphenyls: In vivo and in vitro
modifications of cholesterol and fatty acid biosynthesis. J. Environ. Pathol. Toxicol. 1:813-828
(cited in EPA 1995a).
Lawton, R. W., Ross, M. R., Feingold, J., and Brown, J. F., Jr. 1985. Effects of PCB exposure on
biochemical and hematological findings in capacitor workers. Environ. Health Perspect.
60:165-184 (cited in USAF 1989).
Linzey, A. V. 1988. Effects of chronic polychlorinated biphenyls exposure on growth and
reproduction of second generation white-footed mice (Peromyscus leucopus). Arch. Environ.
Contam. Toxicol. 17:39-45 (cited in USAF 1989).
Litterset, C. L., Farber, T. M., Baker, A. M., et al. 1972. Effect of polychlorinated biphenyls on
hepatic microsomal enzymes in the rat. Toxicol. Appl. Pharmacol. 23:112-122 (cited in IRIS
1995a).
Maroni, M., Columbi, A., Arbosti, G., et al. 1981a. Occupational exposure to polychlorinated
biphenyls in electrical workers. II. Health effects. Br. J. Ind. Med. 38:55-60 (cited in ATSDR
1995).
Maroni, M., Columbi, A., Arbosti, G., et al. 1981b. Occupational exposure to polychlorinated
biphenyls in electrical workers. I. Environmental and blood polychlorinated biphenyls
concentrations. Br. J. Ind. Med. 38:49-54 (cited in ATSDR 1995).
Masuda, Y., and Yoshimura, H. 1984. Polychlorinated biphenyls and dibenzofurans in patients with
Yusho and their toxicological significance: A review. Am. J. Ind. Med. 5:31-44.
Meigs, J. W., Albom, J. J., and Kartin, B. L. 1954. Chloracne from an unusual exposure to Aroclor.
J. Am. Med. Assoc. 154:1417-1418 (cited in ATSDR 1995).
Mes, J., Doyle, J. A., Adam, B. R., et al. 1984. Polychlorinated biphenyls and organochlorine
pesticides in milk and blood of Canadian women during lactation. Arch. Environ. Contam.
Toxicol. 13:217-223 (cited in ATSDR 1995).
Miller, R. W. 1985. Congenital PCB poisoning: A reevaluation. Environ. Health Perspect.
60:211-214 (cited in USAF 1989).
Morgan, R. W., Ward J. M., and Hartman, P. E. 1981. Aroclor® 1254-induced intestinal metaplasia
and adenocarcinoma in the glandular stomach of F344 rats. Cancer Res. 41:5052-5059 (cited
in USAF 1989).
NCI (National Cancer Institute) 1978. Bioassay of Aroclor" 1254 for possible carcinogenicity. NCI
Carcinogenesis Technical Report Series Number 38, NCI-CG-TR-38, DHEW Publication No.
(NIH) 78-838 (cited in USAF 1989).
NIOSH (National Institute for Occupational Safety and Health). 1975. Current Intelligence Bulletin
7, Polychlorinated Biphenyls (PCBs) (cited in USAF 1989).
Norback, D. H., and Weltman, R. H. 1985. Polychlorinated biphenyl induction of hepatocellular
carcinoma in the Sprague-Dawley rat. Environ. Health Perspect. 6:97-105 (cited in USAF
1989).
Overmann, S. R., Kostas, J., Wilson, L. R., Shain, W., and Bush, B. 1987. Neurobehavioral and
somatic effects of perinatal PCB exposure in rats. Environ. Res. 44:56-70 (cited in
USAF 1989).
Poland, A., Knutson, J., Glover, E., et al. 1983. Tumor promotion in the skin of hairless mice by
halogenated aromatic hydrocarbons. In: Weinstein, I. B., Vogel, H. J. eds. Genes and proteins
in oncogenesis. New York, NY: Academic Press, 143-161 (cited in ATSDR 1995).
Price, S. C., Ozalp, S., Wever, R., et al. 1988. Thyroid hyperactivity caused by hypolipidaemic
compounds and polychlorinated biphenyls: The effect of coadministration in the liver and
thyroid. In: Chambers, L., ed. The target organ and the toxic process: Proceedings of the
European Society of Toxicology, Strasbourg, September 17-19. New York: Springer-Verlag,
85-92 (cited in ATSDR 1995).
Puhvel, S. M., Sakamoto, M., Ertl, D. C., et al. 1992. Hairless mice as models for chloracne: A study
of cutaneous changes induced by topical application of established chloracnegens. Toxicol.
Appl. Pharmacol. 64:492-503 (cited in ATSDR 1995).
Rao, C. V., and Banerji, A. S. 1988. Induction of liver tumors in male Wistar rats by feeding
polychlorinated biphenyls (Aroclor® 1260). Cancer Lett. 39:59-67 (cited in USAF 1989).
Ringer, R. K., Aulerich, R. J., and Zabik, M. 1972. Effect of dietary polychlorinated biphenyls on
growth and reproduction of mink. 164th Natl. Meet. Am. Chem. Soc. 12:149 (cited in USAF
1989).
Safe, S. 1980. Metabolism, uptake, storage and bioaccumulation of halogenated aromatic pollutants.
In: Kimbrough, R. D., ed. Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins
and related products. Amsterdam: Elsevier Science Publishers, 81-107.
Sager, D. B. 1983. Effect of postnatal exposure to polychlorinated biphenyls on adult male
reproductive function. Environ. Res. 3:76-94 (cited in USAF 1989).
Sager, D., and Girard, D. 1983. Early postnatal exposure to PCBs and reproductive function in
young and mature adult female rats. Fed. Proc. 42:355. Abstract No. 372 (cited in USAF 1989).
Sanders, O. T., Zepp, R. L., and Kirkpatric, R. L. 1974. Effect of PCB ingestion on sleeping times,
organ weights, food consumption, serum corticosterone and survival of albino mice. Bull.
Environ. Contam. Toxicol. 12:394-399 (cited in ATSDR 1995).
Schaeffer, E., Greim, H., and Goessner, W. 1984. Pathology of chronic polychlorinated biphenyl
(PCB) feeding in rats. Toxicol. Appl. Pharmacol. 75:278-288 (cited in USAF 1989).
Seegal, R. F., Brosch, K. O., and Bush, B. 1986. Regional alterations in serotonin metabolism
induced by oral exposure of rats to polychlorinated biphenyls. Neurotoxicology. 7:155-166
(cited in ATSDR 1995).
Shigematsu, N., Ishimaru, S., Saito, R., Ikeda, T., Matsuba, K., Sugiyama, K., and Masuda, Y. 1978.
Respiratory involvement in polychlorinated biphenyls poisoning. Environ. Res. 16:92-100
(cited in USAF 1989).
Smith, A. B.; Schloemer, J.; Lowry, L. K.; Smallwood, A. W.; Ligo, R. N.; Tanaka, S.; Stringer, W.;
Jones, M.; Hervin, R.; Glueck, C.J. 1982. Metabolic and health consequences of occupational
exposure to polychlorinated biphenyls. Br. J. Ind. Med. 39:361-369 (cited in USAF, 1989).
Spencer, F. 1982. An assessment of the reproductive toxic potential of Aroclor® 1254 in female
Sprague-Dawley rats. Bull. Environ. Contam. Toxicol. 28:290-297 (cited in USAF 1989).
Street, J. C., and Sharma, R. P. 1975. Alteration of induced cellular and humoral immune responses
by pesticides and chemicals of environmental concern: Quantitative studies of
immunosuppression by DDT, Aroclor® 1254, carbofuran, and methylparathion. Toxicol. Appl.
Pharmacol. 32:587-602 (cited in EPA 1995a).
Tanabe, S., Nakagawa, Y, and Tatsukawa, R.. 1981. Absorption efficiency and biological half-life
of individual chlorobiphenyls in rats treated with Kanechlor products. Agric. Biol. Chem.
45:717-726 (cited in ATSDR 1995).
Taylor, P. R., Lawrence, C. E., Hwang, H.-L., and Paulson, A. S. 1984. Polychlorinated biphenyls:
Influence on birthweight and gestation. Am. J. Public Health 74:1153-1154 (cited in USAF
1989).
Treon, J. F., Cleveland, M. D., Cappel, J. W., and Atchley, R. W. 1956. The toxicity of the vapors
of Aroclor®1242 and Aroclor® 1254. Am. Ind. Hyg. Assoc. Q. 17:204-213.
Truelove, J., Grant, D., Mes, J., Tryphonas, H., Tryphonas, L., and Zawidzka, Z. 1982.
Polychlorinated biphenyl toxicity in the pregnant cynomolgus monkey: A pilot study. Arch.
Environ. Contam. Toxicol. 11:583-588 (cited in USAF 1989).
Truelove, J. F., Tanner, J. R., Langlois, I. A., Stapley, R. A., Arnold, D. L., and Mes, J. C. 1990.
Effect of polychlorinated biphenyls on several endocrine reproductive parameters in the female
rhesus monkey. Arch. Environ. Contam. Toxicol. 19:939-943.
Tryphonas, H., Hayward, S., O'Grady, L., et al. 1989. Immunotoxicity studies of PCB (Aroclor®
1254) in the adult rhesus (Macaca mulatta) monkey--preliminary report. Int. J.
Immunopharmacol. 11:199-206.
Tryphonas, H., Luster, M. I., Schiffman, G., et al. 1991a. Effect of chronic exposure of PCB
(Aroclor® 1254) on specific and nonspecific immune parameters in the rhesus (Macaca mulatta)
monkey. Fund. Appl. Toxicol. 16:773-786.
Tryphonas, H., Luster, M. I.,White, K. L., et al. 1991b. Effects of PCB (Aroclor® 1254) nonspecific
immune parameters in rhesus (Macaca mulatta) monkeys. Int. J. Immunopharmacol.
13:639-648.
USAF (U.S. Air Force). 1989. The Installation Restoration Program Toxicology Guide. Volume 3.
Aerospace Medical Division, Air Force Systems Command, Wright-Patterson Air Force Base,
Ohio. pp. 52-1-52-68.
Ward, J. R. 1985. Proliferative lesions of the glandular stomach and liver in F344 rats fed diets
containing Aroclor® 1254. Env. Health. Perspect. 60:89-95.
Weltman, R. H., and Norback, D. H. 1982. Development of hepatocellular and cholangiocellular
neoplasms in the livers of male and female Sprague-Dawley rats after chronic administration
of Aroclor® 1260. Fed. Proc. 41:446. Abstract No. 1029 (cited in USAF 1989).
Yamashita, F. 1977. Clinical features of polychlorbiphenyls (PCB)-induced fetopathy. Paediatrician
6:20 (cited in USAF 1989).
Retrieve Toxicity Profiles
Condensed Version
Last Updated 10/07/97
|
