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Aroclor 1016
CASRN 12674-11-2
Contents
0462
Aroclor 1016; CASRN 12674-11-2
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Aroclor 1016
File On-Line 01/01/1993
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 11/01/1996
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Aroclor 1016
CASRN -- 12674-11-2
Last Revised -- 11/01/1996
The oral Reference Dose (RfD) is based on the assumption that thresholds exist
for certain toxic effects such as cellular necrosis. It is expressed in units
of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily exposure to the human population
(including sensitive subgroups) that is likely to be without an appreciable
risk of deleterious effects during a lifetime. Please refer to the Background
Document for an elaboration of these concepts. RfDs can also be derived for
the noncarcinogenic health effects of substances that are also carcinogens.
Therefore, it is essential to refer to other sources of information concerning
the carcinogenicity of this substance. If the U.S. EPA has evaluated this
substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
Reduced birth weights NOAEL: 0.25 ppm in feed 100 1 7E-5
(0.007 mg/kg-day) mg/kg-day
Monkey Reproductive
Bioassay LOAEL: 1 ppm in feed
(0.028 mg/kg-day)
Barsotti and van Miller,
1984; Levin et al., 1988;
Schantz et al., 1989, 1991
*Conversion Factors: Dams received a total average intake of 4.52 mg/kg (0.25
ppm) or 18.41 mg/kg (1 ppm) throughout the 21.8-month (654 days) dosing
period. These doses are equivalent to 0.007 mg/kg-day and 0.028 mg/kg-day for
the identified NOAEL and LOAEL respectively.
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
Barsotti, D.A. and J.P. van Miller. 1984. Accumulation of a commercial
polychlorinated biphenyl mixture (Aroclor 1016) in adult rhesus monkeys and
their nursing infants. Toxicology. 30: 31-44.
Levin, E.D., S.L. Schantz and R.E Bowman. 1988. Delayed spatial alternation
deficits resulting from perinatal PCB exposure in monkeys. Arch. Toxicol.
62: 267-273.
Schantz, S.L., E.D. Levin, R.E. Bowman et al. 1989. Effects of perinatal PCB
exposure on discrimination-reversal learning in monkeys. Neurotoxicol.
Teratol. 11: 243-250.
Schantz, S.L., E.D. Levin and R.E. Bowman. 1991. Long-term neurobehavioral
effects of perinatal polychlorinated biphenyl (PCB) exposure in monkeys.
Environ. Toxicol. Chem. 10: 747-756.
These are a series of reports that evaluated perinatal toxicity and long-
term neurobehavioral effects of Aroclor 1016 in the same groups of infant
monkeys. Aroclor 1016 is a commercial mixture of polyclorinated biphenyls
(PCBs) devoid of chlorinated dibenzofurans (Barsotti and van Miller, 1984).
Analysis of the commercial feed used for this study revealed contamination
with congeners specific for Aroclor 1248, present in the parts per billion
range. These congeners were present in the control as well as test diets.
Aroclor 1016 was administered to groups of 8 adult female rhesus monkeys via
diet in concentrations of 0, 0.25 or 1.0 ppm for approximately 22 months.
Based on a reported total Aroclor intake of 4.52 and 18.41 mg/kg over the 22-
month exposure period (Schantz et al., 1989, 1991), the low- and high-doses
are estimated to be 0.007 and 0.028 mg/kg-day, respectively. Exposure began 7
months prior to breeding and continued until offspring were weaned at age 4
months. No exposure-related effects on maternal food intake, general
appearance, hematology, serum chemistry (SGPT, lipid, and cholesterol
analyses) or number of breedings were observed (Barsotti and van Miller,
1984). All monkeys had uncomplicated pregnancies, carried their infants to
term and delivered viable offspring. Teratologic examinations were not
performed. Mean birth weights of the infants in the control, 0.007 and 0.028
mg/kg-day dose groups were 521 g, 491 g and 442 g, respectively (Barsotti and
van Miller, 1984). The decrease in birth weight in the high-dose group was
significantly (p<0.01) lower than in controls. Further statistical analysis
of the infant birth weight data by the Agency indicated that gestation length
did not significantly affect birth weight and the distribution of male and
female infants in the various dose groups could not account for the difference
in birth weights among the dose groups. Agency reanalysis of the data
confirmed the significant decrease in body weight for the high-dose infants,
although slightly different average values were obtained. Males that had
sired some infants were exposed to Aroclor 1248, so the birth weight data were
also analyzed excluding these infants. The results for this adjusted data
indicated that control infants weighed 528 g, low-dose infants weighed 486 g,
and high-dose infants weighed 421 g. Even with this adjustment there was
still a significant difference (p<0.01) in birth weight for the high-dose
group when compared with controls. No significant differences between
treatment and control groups were detected in neonatal head circumference or
crown-to-rump measurements. Both exposure groups showed consistent weight
gains, but infant weights in the high-dose group were still lower (864 g) at
weaning, although not significantly different from the controls (896 g).
Hyperpigmentation was present at birth in the low- and high-dose infants but
did not persist once dosing was stopped. This clinical change was determined
not to be a critical adverse effect. The concentration of Aroclor 1016 in
breast milk was higher than the maternal dose. No exposure-related
hematologic effects were observed in the infants during the nursing period
(Barsotti and van Miller, 1984). One of the offspring in the high-dose group
went into shock and died on the day following weaning for unknown reasons
(Schantz et al., 1989, 1991).
Behavioral testing of the infant monkeys was first performed at age 14
months and no overt signs of PCB toxicity were observed (Schantz et al., 1989,
1991). Two-choice discrimination-reversal learning was assessed using simple
left-right spatial position, color and shape discrimination problems, with and
without irrelevant color and shape cues. One of the offspring in the low-dose
group stopped responding early in testing for an unknown reason and could not
be induced to resume; therefore, test results were obtained using 6, 7 and 6
infants in the control, low- and high-dose groups, respectively. The
offspring in the high-dose (0.028 mg/kg-day) group were significantly (p<0.05)
impaired in their ability to learn the spatial position discrimination problem
(i.e., achieved 9 correct choices in 10 trials), requiring more than 2.5 times
as many trials as their age-matched controls. There were no significant
learning differences between these groups on this problem during overtraining
(ability to achieve greater than or equal to 90% correct choices in two
consecutive daily sessions) or position reversals. The only other exposure-
related effect was significantly facilitated learning ability (p<0.05) on the
shape discrimination problem at 0.028 mg/kg-day.
Performance on delayed spatial alternation (a spatial learning and memory
task) was assessed in the offspring monkeys at age 4-6 years (Levin et al.,
1988; Schantz et al., 1991). The two Aroclor-exposed groups were not
significantly different from controls (p<0.05) in test performance. However,
the exposed groups did significantly (p<0.05) differ from each other. The
difference between the two exposed groups was due to a combination of
facilitated performance at the low-dose (0.007 mg/kg-day) and impaired
performance at the high-dose (0.028 mg/kg-day). Although these data are
insufficient for establishing an exposure-effect relation due to the lack of
difference between exposed and control groups, the investigators suggested
that the performance deficit at 0.028 mg/kg-day may have been exposure-
related. The investigators noticed that a paradoxical biphasic effect
occurred on the same test when comparing low-dose and high-dose infants. This
same effect has been observed for lead-exposed monkeys.
To summarize the above, adult monkeys that ingested 0.007 or 0.028 mg/kg-
day doses of Aroclor 1016 for approximately 22 months showed no evidence of
overt toxicity. Effects occurring in the offspring of these monkeys consisted
of hairline hyperpigmentation at greater than or equal to 0.007 mg/kg-day, and
decreased birth weight and possible neurologic impairment at 0.028 mg/kg-day.
Based on the reduced birth weights of prenatally-exposed monkeys, the 0.007
mg/kg-day dose is the NOAEL and the 0.028 mg/kg-day dose is a LOAEL in
monkeys.
The results of the neurobehavioral tests in the monkey offspring at 14
months and 4-6 years of age indicate adverse learning deficits at the 0.028
mg/kg-day maternal dose. Evaluation of these data is complicated by possible
inconsistencies in the outcome of both the discrimination-reversal learning
tests (learning was impaired and facilitated on different problems) and the
delayed spatial alternation test (performance significantly differed between
the two exposed groups, but not between either test group and the control).
However, there is evidence suggesting that deficits in discrimination-reversal
learning and delayed spatial alternation are related to decreased brain
dopamine (Schantz et al., 1991), which has been observed in monkeys orally
exposed to Aroclor 1016 (Seegal et al., 1990, 1991). Behavioral dysfunctions,
including deficits in visual recognition and short-term memory, also have been
observed in infants of human mothers who consumed fish contaminated with PCB
mixtures of unknown composition (Fein et al., 1984a,b; Jacobsen et al., 1985,
1990; Gladen et al., 1988).
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- A 3-fold factor is applied to account for sensitive individuals. The
results of these studies, as well as data for human exposure to PCBs, indicate
that infants exposed transplacentally represent a sensitive subpopulation. A
factor of 3 is applied for extrapolation from rhesus monkeys to human. A full
10-fold factor for interspecies extrapolation is not considered necessary
because of similarities in toxic responses and metabolism of PCBs between
monkeys and humans and the general physiologic similarity between these
species. In addition, the rhesus monkey data are predictive of other changes
noted in human studies such as chloracne, hepatic changes, and effects on
reproductive function. A factor of 3 is applied because of limitations in the
data base. Despite the extensive amount of animal laboratory data and human
epidemiologic information regarding PCBs, the issue of male reproductive
effects is not directly addressed and two-generation reproductive studies are
not available. As the study duration was considered as somewhat greater than
subchronic, but less than chronic, a partial factor of 3 is used to account
for extrapolation from a subchronic exposure to a chronic RfD.
MF -- None
___I.A.4. ADDITIONAL STUDIES / COMMENTS (ORAL RfD)
Male pig-tailed macaques [Macaca nemistrina], (number not reported, age 3-
7 years, 5-9 kg initial body weight) were administered Aroclor 1016 dissolved
in corn oil on bread in doses of 0, 0.8, 1.6 or 3.2 mg/kg-day for 20 weeks
(Seegal et al., 1991). There were no overt signs of intoxication or exposure-
related effects on body weight gain. Neurochemical analyses of various
regions of the brain were performed following termination of exposure. Dose-
related decreased concentrations of dopamine were observed in the caudate
nucleus, putamen, SUBSTantia nigra, and hypothalamus, but not in the globus
pallidus or hippocampus. There were no exposure-related changes in
concentrations of norepinephrine, epinephrine, or serotonin. Other neurologic
endpoints were not evaluated.
Subchronic oral studies of Aroclor 1016 have been performed in species
other than monkeys. These species were tested at doses higher than the 0.007
and 0.028 mg/kg-day doses fed to monkeys in the principal studies.
Groups of 10 female Sprague-Dawley rats (age not reported, body weight
approximately 225-250 g at start) were fed 0, 1, 5 or 50 ppm Aroclor 1016 in
the diet for 5 months (Byrne et al., 1988). The Aroclor was dissolved in
acetone that was evaporated from the diet prior to feeding. Using a rat food
consumption factor of 0.05 kg food/kg bw (U.S. EPA, 1987), the doses are
estimated to be 0, 0.05, 0.25 and 2.5 mg/kg-day. Serum levels of adrenal
cortical hormones were evaluated four times throughout the treatment period.
Adrenal dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHS)
levels were significantly (p<0.05) reduced at all treatment levels after
approximately 100 days of exposure. Serum corticosterone (the principal
glucocorticoid in rats), adrenal weight, adrenal histology, and nonadrenal
endpoints other than food consumption were not evaluated. Food consumption
did not significantly differ between and among control and treatment groups.
Because insufficient information is available to determine whether the
decreases in circulating adrenal hormones were physiologically significant, it
is uncertain whether the doses are NOAELs or LOAELs for Aroclor 1016 in rats.
Male Balb/c mice (18-20 g body weight) were fed Aroclor 1016 mixed in diet
at concentrations of 0 or 5 ppm for 3 or 6 weeks (Loose et al., 1978). Using
a mouse food consumption factor of 0.13 kg food/kg bw (U.S. EPA, 1987), the
dose is estimated to be 0.65 mg/kg-day. Sensitivity to Salmonella typhosa
endotoxin (15 mice per endotoxin dose) and resistance to infection by
Plasmodium berghei (malaria parasitemia; number of mice not reported) were
evaluated. Sensitivity to the endotoxin was significantly (p<0.05) increased
after 3 weeks of exposure as indicated by endotoxin LD50 values of 152 and 844
ug in the Aroclor-exposed and control groups, respectively. Sensitivity to
the endotoxin after 6 weeks of Aroclor exposure was not evaluated. There were
no significant (p<0.05) effects of Aroclor exposure for 3 or 6 weeks on
malaria lethality as indicated by post-inoculation survival time. No other
endpoints were evaluated in this study. When injected into neonates, splenic
cells from C57Bl/6 male mice exposed to 167 ppm (21.71 mg/kg-day) dietary
Aroclor 1016 for 3 weeks elicited a greater graft-versus-host reaction than
controls (Silkworth and Loose, 1978). Based on the decreased resistance to
infection leading to death, 0.65 mg Aroclor 1016/kg-day suggests a LOAEL for
immunotoxicity for subchronic exposure in male mice.
Aulerich and Ringer (1977) performed a breeding study in which groups of 8
female and 2 male adult pastel mink were fed diets containing 0 or 2 ppm
Aroclor 1016 for 39 weeks or until the kits were 4 weeks of age. The Aroclor
was dissolved in acetone which was evaporated from the diet prior to feeding.
Using assumed values of 150 g/day for food consumption and 0.8 kg for body
weight for female mink (Bleavins et al., 1980), the estimated dose of Aroclor
1016 is 0.4 mg/kg-day. Monthly determinations showed no statistically
significant differences (p<0.05) between the control and treated mink in body
weight gain, hemoglobin, and hematocrit. Additionally, tabulated data showed
no treatment-related effects on female survival, numbers of females mated,
number of females that gave birth, number of kits born alive or dead, number
of births per female, average birth weight or number of kits alive at 4 weeks.
The evidence for lack of treatment-related effects on body weight, hematology,
reproduction and survival suggests that 0.4 mg/kg-day is a NOAEL for Aroclor
1016 in mink.
Groups of adult Pastel mink were fed a diet containing 0 ppm (24 females
and 6 males) or 20 ppm (12 females and 3 males) Aroclor 1016 during a 247-day
breeding study (Bleavins et al., 1980). Aroclor was dissolved in acetone
which was evaporated from the diet prior to feeding. Using assumed values of
150 g/day for food consumption and 0.8 kg for body weight for female mink
reported by the investigators, the estimated dose of Aroclor 1016 is 3.8
mg/kg-day. There were no deaths in the exposed or control males. Mortality
was higher in the exposed females [25% (3/12) compared with 12.5% (3/24) in
controls], but no clear difference in survival time was observed. Necropsies
for gross abnormalities were performed on all control and treated mink that
died; these showed effects only in the treated mink consisting of emaciation
characterized by an almost complete absence of body fat. Histologic
examinations were not performed. The incidence of mated females giving birth
was reduced in the exposed group [44.4% (4/9) compared with 76.2% (16/21) in
controls], but average gestation length, live births and birth weight did not
significantly differ (p>0.05) between exposed and control groups. Body weight
at age 4 weeks, average number of infants per lactating female and infant
biomass (average body weight gain through age four weeks x average number of
infants raised per lactating female) were significantly (p<0.05) reduced in
the exposed group. Mortality during the first 4 weeks of life was increased
in the exposed group [56.0% (14/25) compared with 24.1% (19/79) in controls].
The investigators noted that the adverse effects on reproduction do not appear
to be due to an effect on spermatogenesis, since PCB-treated male mink have
had acceptable levels of reproduction when mated to untreated females in other
studies. The evidence for impaired reproduction and increased maternal and
postnatal mortality suggests that 3.8 mg Aroclor 1016/kg-day is an FEL in
mink. Although the FEL from this study and NOEL of 0.4 mg/kg-day from
Aulerich and Ringer (1977) suggest that the dose-severity slope for Aroclor
1016 in mink is steep, neither study tested sufficient numbers of animals or
dose levels to allow definitive conclusions to be drawn.
Dermal lesions including skin irritation, chloracne and increased
pigmentation of skin and nails have been observed in humans occupationally
exposed to Aroclor 1016 and other Aroclor formulations by both inhalation and
dermal routes (Fischbein et al., 1979, 1982, 1985; Ouw et al., 1976; Smith et
al., 1982). However, insufficient data are available to determine possible
contributions of Aroclor 1016 alone, extent of direct skin exposure and
possible contaminants in these occupational studies.
Decreased birth weight has also been reported in infants born to women who
were occupationally exposed to Aroclor 1016 and other Aroclor formulations
(Taylor et al., 1984, 1989), ingested PCB-contaminated fish (Fein et al.,
1984a,b) and ingested heated Kanechlor PCBs during the Yusho and Yu-Cheng
incidents (Rogan, 1989; Yamashita, 1977). Due to uncertainties regarding
actual sources of PCB exposure, and other confounding factors and study
limitations, the decreases in human birth weight cannot be solely attributed
to PCBs, particularly specific PCB mixtures. However, due to the consistency
with which the effect has been observed, the human data are consistent with
the Aroclor 1016-induced decreased birth weight in monkeys reported in the
principal studies.
The human data available for risk assessment of Aroclor 1016 are useful
only in a qualitative manner. Studies of the general population exposed to
PCBs by consumption of contaminated food, particularly neurobehavioral
evaluations of infants exposed in utero and/or through lactation, have been
reported, but the original PCB mixtures, exposure levels and other details of
exposure are not known (Kreiss et al., 1981; Humphrey, 1983; Fein et al.,
1984a,b; Jacobson et al., 1984a, 1985, 1990a,b; Rogan et al., 1986; Gladen et
al., 1988). Most of the information on health effects of PCB mixtures in
humans is available from studies of occupational exposure. Some of these
studies examined workers who had some occupational exposure to Aroclor 1016,
but in these studies concurrent exposure to other Aroclor mixtures nearly
always occurred, exposure involved dermal as well as inhalation routes (the
relative contribution by each route was not known), and monitoring data were
lacking or inadequate (Fischbein et al., 1979, 1982, 1985; Fischbein, 1985;
Warshaw et al., 1979; Smith et al., 1982; Lawton et al., 1985).
Information specifically on the oral absorption of Aroclor 1016 is not
available, but studies of individual congeners and PCB mixtures of higher
chlorine content in animals indicate, in general, that PCBs are readily and
extensively absorbed. These studies have found oral absorption efficiency on
the order of 75 to >90% in rats, mice, monkeys and ferrets (Albro and
Fishbein, 1972; Allen et al., 1974; Tanabe et al., 1981; Bleavins et al.,
1984; Clevenger et al., 1989). A study of a PCB mixture containing 54%
chlorine provides direct evidence of absorption of PCBs in humans after oral
exposure (Buhler et al., 1988), and indirect evidence of oral absorption of
PCBs by humans is available from studies of ingestion of contaminated fish by
the general population (Schwartz et al., 1983; Kuwabara et al., 1979). There
are no quantitative data regarding inhalation absorption of PCBs in humans but
studies of exposed workers suggest that PCBs are well absorbed by the
inhalation and dermal routes (Maroni et al., 1981a,b; Smith et al., 1982;
Wolff, 1985). PCBs distribute preferentially to adipose tissue and
concentrate in human breast milk due to its high fat content (Jacobson et al.,
1984b; Ando et al., 1985).
The metabolism of PCBs following oral and parenteral administration in
animals has been extensively studied and reviewed, but studies in animals
following inhalation or dermal exposure are lacking (Sundstrom and Hutzinger,
1976; Safe, 1980; Sipes and Schnellmann, 1987). Information on metabolism of
PCBs in humans is limited to occupationally exposed individuals whose intake
is derived mainly from inhalation and dermal exposure (Jensen and Sundstrom,
1974; Wolff et al., 1982; Schnellmann et al., 1983; Safe et al., 1985; Fait et
al., 1989). In general, metabolism of PCBs depends on the number and position
of the chlorine atoms on the phenyl rings of the constituent congeners (i.e.,
congener profile of the PCB mixture) and animal species. Although only
limited data are available on metabolism of PCBs following inhalation
exposure, there is no reason to suspect that PCBs are metabolized differently
by this route.
Data exist on the in vitro hepatic metabolism and in vivo metabolic
clearance of 2,2',3,3',6,6'-hexachlorobiphenyl and 4,4'-dichlorobiphenyl
congeners in humans, monkeys, dogs, and rats (Schnellmann et al., 1985). Both
of these congeners are present in Aroclor 1016, but the hexachlorobiphenyl is
only a minor constituent. For each congener, the Vmax values for metabolism
in the monkey, dog and rat are consistent with the respective metabolic
clearance values found in vivo. Thus, the kinetic constants for PCB
metabolism obtained from the dog, monkey, and rat hepatic microsomal
preparations were good predictors of in vivo metabolism and clearance for
these congeners. In investigations directed at determining which species most
accurately predicts the metabolism and disposition of PCBs in humans, the in
vitro metabolism of these congeners was also studied using human liver
microsomes (Schnellmann et al., 1983, 1984). Available data suggest that
metabolism of PCBs in humans most closely resembles that of the monkey and
rat. For example, the in vitro apparent Km and Vmax for humans and monkeys
are comparable. These studies show consistency between the in vitro and in
vivo findings and collectively indicate that metabolism of the two congeners
is similar in monkeys and humans.
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Medium
Data Base -- Medium
RfD -- Medium
Confidence in the critical studies is rated medium since essentially only
one group of monkeys has been examined. The initial study was well conducted
in a sensitive animal species (rhesus monkeys) that closely resembles humans
for many biological functions. These studies evaluated many sensitive
endpoints of PCB toxicity and the effects observed have also been documented
for human exposure. Many sophisticated reproductive and neurologic tests were
performed over 6 years and many clinical chemistry determinations were
conducted on the dams during the exposure period. Very extensive analyses of
feed samples and tissue samples from dosed monkeys were performed. Although
contamination of the control laboratory primate diet with PCBs other than
those found in Aroclor 1016 was detected, the level of contamination was at
the level of parts per billion and dosing of Aroclor 1016 was in the parts per
million range. Because the contamination was consistent across all treatment
groups and controls, quantitative comparison of adverse effects can be made.
The investigators carefully documented the levels of test material and
contaminant throughout the exposure and post-exposure period in animal
tissues. Because the system of placentation, hemothelial-chorial with
bidiscoidal distribution, is similar for Rhesus monkeys and humans, it is felt
that toxic events that are induced during gestation for Rhesus monkeys will be
highly predictive of similar events in humans. Historically, developmental
neurobehavioral effects observed in rhesus monkeys are predictive of similar
effects in humans. Although these studies were performed in an academic
setting prior to the era of Good Laboratory Practices- Quality Control-Quality
Assurance, the study report provides ample documentation of the experimental
protocol and quality of data collected. While the group sizes for this study
are small (8 monkeys/group) when compared with the standards for rodent
studies they are within the acceptable range for studies of large mammalian
species as determined by EPA.
The data base for PCBs in general is extensive. Studies examining Aroclor
1016 have been performed in rhesus monkeys, mice, rats and mink. However,
despite the extensive amount of data available only medium confidence can be
placed in the data base at this time. It is acknowledged that mixtures of
PCBs found in the environment do not match the pattern of congeners found in
Aroclor 1016, therefore the RfD is only given medium confidence. For those
particular environmental applications where it is known that Aroclor 1016 is
the only form of PCB contamination, use of this reference dose may rate high
confidence. For all other applications only medium confidence can be given.
The U.S. EPA recognizes that there is a diversity of opinion among scientists
concerning the use of the monkey studies for determining PCB toxicity.
However, all of the studies in the vast data base for this chemical mixture
support the conclusions reached in this document.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- U.S. EPA, 1980, 1984, 1989, 1990
Agency Work Group Review -- 02/21/1990, 03/25/1992, 06/23/1992, 09/24/1992, 10/15/1992,
11/04/1992, 02/11/1993
Verification Date -- 11/04/1992
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Aroclor 1016
CASRN -- 12674-11-2
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Aroclor 1016
CASRN -- 12674-11-2
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. BIBLIOGRAPHY
Substance Name -- Aroclor 1016
CASRN -- 12674-11-2
Last Revised -- 02/01/1993
__VI.A. ORAL RfD REFERENCES
Albro, P.W. and L. Fishbein. 1972. Intestinal absorption of polychlorinated
biphenyls in rats. Bull. Environ. Contam. Toxicol. 8: 26-31.
Allen, J.R. and D.H. Norback. 1976. Pathobiological responses of primates to
polychlorinated biphenyl exposure. In: Proceedings of the National Conference
on Polychlorinated Biphenyls. EPA 560/6-75-004. p. 43-49.
Allen, J.R., L.J. Abrahamson and D.H. Norback. 1973. Biological effects of
polychlorinated biphenyls and triphenyls on the subhuman primate. Environ.
Res. 6: 344-354.
Allen, J.R., D.H. Norback and I.C. Hsu. 1974. Tissue modifications in
monkeys as related to absorption, distribution, and excretion of
polychlorinated biphenyls. Arch. Environ. Contam. Toxicol. 2: 86-95.
Ando, M., H. Saito and I. Wakisaka. 1985. Transfer of polychlorinated
biphenyls (PCBs) to newborn infants through the placenta and mothers' milk.
Arch. Environ. Contam. Toxicol. 14: 51-57.
Aulerich, R.J. and R.K. Ringer. 1977. Current status of PCB toxicity to
mink, and effect on their reproduction. Arch. Environ. Contam. Toxicol. 6:
279-292.
Barsotti, D.A. 1980. PhD Thesis. "Gross, Clinical, and Reproductive Effects
of Polychorinated Biphenyls in the Rhesus Monkey", August, 1980. Available
through the University Library, University of Wisconsin, Madison, Wisconsin.
Barsotti, D.A. and J.P. Van Miller. 1984. Accumulation of a commercial
polychlorinated biphenyl mixture (Aroclor 1016) in adult rhesus monkeys and
their nursing infants. Toxicology. 30: 31-44.
Barsotti, D.A., R.J. Marlar and J.R. Allen. 1976. Reproductive dysfunction
in rhesus monkeys exposed to low levels of polychlorinated biphenyls (Aroclor
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__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Aroclor 1016
CASRN -- 12674-11-2
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
08/01/1991 I.A. Oral RfD now under review
08/01/1992 I.A. Work group review dates added
10/01/1992 I.A. Work group review date added
12/01/1992 I.A. Work group review dates added
01/01/1993 I.A. Oral RfD assessment on-line
01/01/1993 VI.A. Oral RfD references on-line
02/01/1993 VI.A. Oral RfD references corrected
03/01/1993 I.A.6. Work group review date added
09/01/1993 I.A. Oral RfD noted as going to be externally peer reviewed
11/01/1993 I.A. Note revised
05/01/1994 I.A. Peer review note removed; peer review May 24-25
11/01/1996 I.A.7. Primary contact's office changed
VIII. SYNONYMS
Substance Name -- Aroclor 1016
CASRN -- 12674-11-2
Last Revised -- 01/01/1993
12674-11-2
AROCLOR 1016
HSDB 6352
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0462.HTM
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