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Aroclor 1248
CASRN 12672-29-6
Contents
0649
Aroclor 1248; CASRN 12672-29-6
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 1248
File On-Line 04/01/1994
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) message 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 1248
CASRN -- 12672-29-6
The health effects data for Aroclor 1248 were reviewed by the U.S. EPA
RfD/RfC Work Group and determined to be inadequate for the derivation of an
oral RfD. The verification status for this chemical currently is NOT
VERIFIABLE. For additional information on the health effects of this
chemical, interested parties are referred to the U.S. EPA documentation listed
below.
NOT VERIFIABLE status indicates that the U.S. EPA RfD/RfC Work Group
deemed the data base at the time of review to be insufficient to derive an
oral RfD according to the current Agency guidelines. This status does not
preclude the use of information in cited references for assessment by others.
Derivation of an oral RfD for Aroclor 1248 is not recommended because a
Frank Effect (death of an infant) was noted at the lowest dose tested in a
sensitive animal species, rhesus monkeys (Macaca mulatta). In general, Rhesus
monkeys have shown adverse effects to PCB mixtures at doses 10-fold lower than
in other species. The data indicated a dose-response relationship for this
effect.
Schantz et al. (1989) evaluated neurobehavioral performance in offspring
of rhesus monkeys that had been exposed to 0.03, 0.1 and 0.2 mg/kg-day of
dietary Aroclor 1248 for different durations. Group I consisted of infants
whose dams had received 0.03 mg/kg-day. Of the seven dams for this group, six
delivered viable offspring. Necropsy of the infant who died at the time of
weaning showed signs of PCB intoxication that included thymic atrophy and skin
hyperpigmentation. Group II consisted of offspring of 4/8 females fed 0.1
mg/kg-day of Aroclor 1248. Of the eight dams of this group, one delivered a
dead infant and one delivered an infant that died shortly after weaning with
signs of PCB intoxication. Group III consisted of offspring of 3/7 females
fed 0.2 mg/kg-day of Aroclor 1248. Of the seven females that were dams in
this group, only three delivered live infants. Information on maternal
toxicity was not provided in the report. Mild dermatological lesions and
hyperpigmentation about the hairline developed in offspring in all treated
groups during nursing, but no signs of toxicity were evident at the time of
neurological testing (age 14 months). Offspring weights at birth and weaning
were significantly reduced in Group III. Offspring in Groups I and II did not
differ from controls on spatial, color or shape in two-choice discrimination
reversal learning tests, but decreased performance on a shape discrimination
problem was observed in Group III when irrelevant cues were inserted. On the
basis of thymic atrophy and chloracne and death of 1 of 7 infants, it is
concluded that 0.03 mg/kg-day represents a FEL for developmental effects.
Adult female Rhesus monkeys were fed 0, 2.5 or 5 ppm (0, 0.1 and 0.2
mg/kg-day) of Aroclor 1248 incorporated in food pellets for up to 14 months
(Barsotti et al., 1976; Barsotti, 1980). The exposure period ran from 7
months prior to breeding through gestation, and then for an additional 4
months until the infants were weaned. Some treated females began showing skin
changes, such as hyperpigmentation and alopecia, characteristic signs of PCB
intoxication, during the first 2 months of dosing. Monkeys with less body fat
were the first to show clinical signs, regardless of the dose group to which
they were assigned. All treated females showed signs of PCB intoxication to
some degree by 6 months. A progressive increase in SGPT values was observed
for all treated monkeys and this increase was found to be statistically
significant (p<0.05) by the 22nd month of the study, even though dosing
stopped at the end of the l4th month. One female in each dose group developed
severe shigellosis and died, and other dosed females developed clinical signs
of shigellosis but did not die. Necropsies of deceased monkeys showed focal
necrosis and lipid deposition of the liver, as well as marked subcutaneous
edema. Increased menstrual duration was noted as well as occasional
amenorrhea.
For the experimental breeding trial, conducted during the dosing period,
all low-dose monkeys (8/8) conceived; 3/8 aborted and 5/8 delivered live
infants. However, 3 of these 5 liveborn infants showed clinical signs of PCB
toxicity and, being unable to withstand the stress of weaning, died when
separated from their dams. Among the high-dose monkeys, 6/8 conceived. Among
these six conceptions, four ended in abortion, one infant went to term, but
was stillborn. Only one normal birth occurred among this group; however, at
the time of weaning, this infant showed clinical signs of PCB toxicity and
died.
The investigators realized that PCB mixtures might have latent effects
that could appear long after dosing had ceased. Thus, they included three
additional recovery breeding periods after dosing had been completed.
The first recovery breeding trial occurred approximately 22 months after
the initiation of Aroclor 1248 dosing and 8 months after dosing had stopped.
For the low-dose dams, 8/8 conceived. One of these eight conceptions resulted
in abortion. Of the seven livebirths, two infants died at or before weaning.
Among the high-dose mothers, 7/7 conceived. There was one abortion and one
stillbirth among this group of seven mothers, and five livebirths. Among the
group of five livebirths, three infants died at or before weaning.
A second recovery breeding trial was conducted approximately 36 months
after the completion of Aroclor 1248 dosing. Among the low-dose mothers, 5/7
conceived. There was one stillbirth and four live births. All four of the
liveborn infants survived past weaning and were available for behavioral
testing at 14 months and 4 years of age. Among the high-dose mothers, 4/6
conceived for this breeding trial. There were no abortions among the four
conceptions, but one stillbirth did occur; there were three livebirths.
The third recovery breeding trial was conducted 55 months after the
completion of Aroclor 1248 dosing. Among the low-dose dams, 7/7 conceived.
There were no abortions among this group but two stillbirths did occur. All
five liveborn infants survived past weaning. For the high-dose mothers, only
five had normal reproductive cycles and 4/5 conceived. Among the four
conceptions, one ended in abortion, another infant was stillborn and two were
born live.
In the first recovery breeding trial the average birth weights for the
dosed groups were found to be reduced when compared with controls. For the
second recovery breeding trial, the mean weight of the test group infants was
15 and 22% below the control group.
Results of this prolonged recovery period revealed impairment of
reproductive function in female Rhesus monkeys lasting for more than 4 years
after dosing ceased. In the groups of infants for which birth-weight data are
available, a significant reduction in mean birth weight for PCB-exposed
infants is evident.
Thomas and Hinsdill (1978) performed immunologic tests after Rhesus
monkeys had been fed 0, 2.5 and 5 ppm dietary Aroclor 1248 for 11 months. All
treated monkeys developed facial acne and edema and swollen eyelids to varying
degrees after 6 months, with pronounced alopecia occurring in the 0.2 mg/kg-
day group. Following the treatment period, the monkeys were inoculated with
sheep red blood cells (SRBC) and tetanus toxoid. Anti-SRBC antibody titers
were significantly reduced in the 0.2 mg/kg-day group at weeks 1 and 12 after
inoculation, but antibody response to tetanus toxoid was not affected by
treatment at either dosage level.
Groups of three female New Zealand white rabbits were fed 0, 10, 100 or
250 ppm of Aroclor 1248 for 4 weeks and bred with untreated males (Thomas and
Hinsdill, 1980). No maternal toxicity was evident. Body-weight gain was
significantly reduced in the offspring in the high-dose group.
Barsotti, D.A., R.J. Marlar and J.R. Allen. 1976. Reproductive dysfunction
in rhesus monkeys exposed to low levels of polychlorinated biphenyls (Aroclor
1248). Food Cosmet. Toxicol. 14: 99-103.
Barsotti, D.A. 1980. Gross, Clinical, and Reproductive Effects of
Polychlorinated Biphenyls in the Rhesus Monkey. August. Ph.D. Thesis,
available through the University Library, University of Wisconsin, Madison,
WI.
Schantz, S.L., E.D. Levin, R.W. Bowman et al. 1989. Effects of perinatal PCB
exposure on discrimination-reversal learning in monkeys. Neurotoxicol.
Teratol. 11: 243-250.
Thomas, P.T. and R.D. Hinsdill. 1978. Effect of polychlorinated biphenyls on
the immune responses of rhesus monkeys and mice. Toxicol. Appl. Pharmacol.
44: 41-51.
Thomas, P.T. and R.D. Hinsdill. 1980. Perinatal PCB exposure and its effect
on the immune system of young rabbits. Drug Chem. Toxicol. 3: 173-184.
Agency Work Group Review -- 08/12/1992, 11/04/1992, 06/16/1993, 07/20/1993
EPA Contacts:
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 1248
CASRN -- 12672-29-6
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Aroclor 1248
CASRN -- 12672-29-6
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 1248
CASRN -- 12672-29-6
Last Revised -- 04/01/1994
__VI.A. ORAL RfD REFERENCES
Barsotti, D.A., R.J. Marlar and J.R. Allen. 1976. Reproductive dysfunction
in rhesus monkeys exposed to low levels of polychlorinated biphenyls (Aroclor
1248). Food Cosmet. Toxicol. 14: 99-103.
Barsotti, D.A. 1980. Gross, Clinical, and Reproductive Effects of
Polychlorinated Biphenyls in the Rhesus Monkey. August. Ph.D. Thesis,
available through the University Library, University of Wisconsin, Madison,
WI.
Schantz, S.L., E.D. Levin, R.W. Bowman et al. 1989. Effects of perinatal PCB
exposure on discrimination-reversal learning in monkeys. Neurotoxicol.
Teratol. 11: 243-250.
Thomas, P.T. and R.D. Hinsdill. 1978. Effect of polychlorinated biphenyls on
the immune responses of rhesus monkeys and mice. Toxicol. Appl. Pharmacol.
44: 41-51.
Thomas, P.T. and R.D. Hinsdill. 1980. Perinatal PCB exposure and its effect
on the immune system of young rabbits. Drug Chem. Toxicol. 3: 173-184.
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Aroclor 1248
CASRN -- 12672-29-6
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
09/01/1992 I.A. Oral RfD now under review
12/01/1992 I.A. Work group review date added
07/01/1993 I.A. Work group review date added
08/01/1993 I.A. Work group review date added
04/01/1994 I.A. Oral RfD message on-line
04/01/1994 VI.A. Oral RfD references on-line
11/01/1996 I.A. Contact's office changed
VIII. SYNONYMS
Substance Name -- Aroclor 1248
CASRN -- 12672-29-6
Last Revised -- 09/01/1992
12672-29-6
Aroclor 1248
HSDB 6356
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0649.HTM
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