Evaluation of the Potential Carcinogenicity of
7,l2-Dimethyibenz(a)anthracene (57-97-6)
Syracuse Research Corp., NY
Prepared for:
Environmental Protection Agency, Washington, DC
Jun 88
L
J
U.S. DEPARTMENT OF COMMERCE
National Technical Information Service
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UNITED STATES . EPA/eoo/3-91/117
ENVIRONMENTAL PROTECTION JUNE 1988
AGENCY FINAL
RESEARCH AND
DEVELOPMENT
EVALUATION OF THE POTENTIAL CARCINOGENICITY OF
7.12-DIMETHYLBENZ(A)ANTHRACENE
(57-97-6)
IN SUPPORT OF REPORTABLE QUANTITY ADJUSTMENTS
PURSUANT TO CERCLA SECTION 102
PREPARED FOR
OFFICE OF EMERGENCY AND REMEDIAL RESPONSE
OFFICE OF SOLID WASTE AND EMERGENCY RESPONSE
PREPARED BY
CARCINOGEN ASSESSMENT GROUP
OFFICE OF HEALTH AND
ENVIRONMENTAL ASSESSMENT
WASHINGTON, D.C. 20460
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TECHNICAL REPORT DATA
'•«» completr
i REPORT NO.
EPA/600/8-91/117
2.
PB93-1853«b
4. TITLE AND SUBTITLE
Evaluation of the Potential Carcinogenicity of
7,i2-Di;.ietnylbenz{a}Anthracene (57-97-6)
S. REPORT DATE
June 19RR
ft. PERFORMING ORGANIZATION CODE
7 AUTHORIS)
Syracuse Research Corporation
Environmental Monitoring & Services. Inr
«. PERFORMING ORGANIZATION REPORT NO.
OHEA-C-073-Q9?
». PERFORMING ORGANIZATION NAME ANO ADDRESS
^ r* r ^^r-v^naw^^ ^^T-» ^*n«v • ^^m v v^^w '»^»-^^ ^^ - ^ w •"" vr *f " " ^ i^^v
Syracuse Research Corporation, Syracuse, NY
Environmental Monitoring & Services, Inc. (now ABB
Environmental Services, Inc.), Washington, DC
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11-CONTRACT/GRANT NO
68-03-3112
68-03-3182
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Office of Health and Environmental Assessment
Carcinogen Assessment Group (RD-689)
U.S. Environmental Protection Agency
Washington, DC 20460
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14. SPONSORING AGENCY CODE
EPA/600/021
is. SUPPLEMENTARY NOTES
1«. ABSTRACT
7,12-Dimethyfcenz(a)anthracene is a probable human carcinogen, classified as wekjht-
of-evktence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S.
EPA. 1986a). Evidence on potential carcrncgenicrty from animal studies is 'Sufficient,' and
the evidence from human studies is *No Data.*
The potency factor (F) for 7.12-dimethylbenz(a)anthracene is estimated to be
540 (mg/kg/day), placing it in potency group 1 according to the CAG's methodology for
evaluating potential carcinogens (U.S. EPA, 1986b).
Combining the wekjht-of-evidence group and the potency group, 7,12-
dlmethy1befiz(a)anthracene is assigned a 'HIGH* hazard ranking for the purposes of RQ
adjustment.
17
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ii
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PREFACE
This report summarizes and evaluates information on the potential
carcinogenicity of a substance designated as hazardous under Section 101 (14)
of the Comprenensive Environmental Response, Compensation and Liability Act of
1980 (CERCLA). Pertinent epidemiologic and toxicclogic data were obtained
through on-line searches and from hard-copy sources. On-line searches were
extended as far back as the data bases would allow. Retrieval of historical
data was accomplished through searches of hard-copy sources and bibliographies
of relevant publications. Every attempt has been made to rely upon primary
publications as opposed to data summaries or abstracts contained in secondary
sources such as monographs, surveys, review articles, criteria documents, etc.
The on-line data bases that were searched included CHEMLINE (National Library
of Medicine [NLM]). RTECS (NLM), Toxicology Data Bank (KLM), TOXLIME (NLM),
CANCERLXNE (NLM), and Chemical Abstracts (DIALOG Information Services).
Unpublished data were not used in this evaluation.
The Agency's Methodology for obtaining, evaluating, and ranking CERCLA
potential carcinogens is described in the Technical Background Document to
Support Rulemaking Pursuant to CERCLA Section 102, Volume 3, April 26, 1988
(EPA/600/8-99/053). This document revises the previous methodology document
of 1986 according to the public comments received on the March 16, 1987 Notice
of Proposed Rulemaking (52 FR 8140). The Methodology for Adjusting reportable
quantities is described in the Technical Background Document to Support
Rulemaking Pursuant to CERCLA Section 102, Volume 1, March, 1985, and is also
summarized in Volume 2, August, 1986, and Volume 3, December, 1986. The EPA's
Office of Emergency and Remedial Response (OERR) has considered this
evaluation in adjusting reportable quantities pursuant to CERCLA Section 102.
This report is consistent with the revised methodology. It draws largely on
information supplied by the Syracuse Research Corporation in 1984 under EPA
Contract Ho. 68-03*3112. Due to the amount of time elapsed between the
original work performed by Syracuse Research Corporation and the present
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effort to produce this document. Environmental Monitoring 4 Services, Inc.,
under EPA Contract No. 68-03-3182, has been involved in an extensive review of
ail the Syracuse documents. In some cases, this review involved updating the
ir.forsation provided but it was primarily a quality assurance effort. The
present document is a result of this effort.
IV
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ABSTRACT
7.12-Dimethylbenz(a)anthracene is a probable human carcinogen, classified as
weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk
Assessment (U.S. EPA, 1986a). Evidence on potential carcinogenicity from animal
studies is •Sufficient," and the evidence froa human studies is "No Data."
The potency factor (F) for 7,12-diaethylbenz(a)anthracene is estimated to be
540 (Bg/kg/day)"^, placing it in potency group 1 according to the CAG's
methodology for evaluating potential carcinogens (U.S. EPA, 19S6b).
Combining the veight-of-evidence group and the potency group, 7,12-dimethyl-
bet^ a) anthracene is assigned a "HIGH" hazard ranking for the purposes of RQ
adjustment.
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TABLE OF CONTENTS
Page
1.0 WEIGHT OF EVIDENCE 1-1
1.1 ANIHAL STUDIES 1-1
1.2 HUMAN STUDIES : 1-2
1.3 WEIGHT-OF-EVIDENCE ASSESSMENT 1-2
2.0 POTENCY 2-1
3.0 HAZARD RANKING 3-1
4.0 REFERENCES 4-1
APPENDIX: SUMMARY OF SIGNIFICANT HUMAN AND/OR ANIMAL STUDIES
TABLES
Table 2-1. DERIVATION OF POTENCY FACTOR (F) 2-2
vi
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1.0 WEIGHT OF EVIDENCE
1.1 ASIHAL STUDIES
The carcinogenic activity of 7,12-dimethylbenz(a)anthracene (DKBA) in animals
has been very veil documented. 7,12-Dimethylbenz(a)anthracene produces tumors
in multiple target organs in several animal species when administered by
various routes. When applied to the skin of mice, 7,12-dimethylbenz(a)anthra-
cene can act as both a complete carcinogen and as a tumor initiator (Grube et
•1., 1975; Lav, 1941; Roe, 1956; Terracini et al., 1960; Klein. 1956; Hovell,
1962; Slaga et al., 1974). Skin application of 7,12-dimethylbenz(a)anthracene
also produces tumors in guinea pigs (Pavlovski et al., 1976; Berenblun, 1949;
Edgecomb and Mitchelich, 1962) and rats (Albert et al., 1978). Sarcomas
developing at the site of injection are frequently observed vith 7.12-
dimethylbenz(a)anthracene administered to rats and mice (Flesher et al., 1976;
Buu-hoi, 1964). Intratracheal instillation o- implantation of 7,12-
diaethylbenz(a)anthracene has produced lung tumors in dogs (Paladugu et al..
1980; Staub et al.. 1965; Beattie et al., 1961) and hamsters (Delia Porta et
al.. 1958).
Manoary cancer induced in rodents by 7,12-dimethylbenz(a)anthracene has become
an important model system for the study of human breast cancer (Grisvold et
al.. 1966; Pearson. 1973; Dao, 1964). Huggins et al. (1962) demonstrated that
a single intragastric fee'ding of 20 mg 7,12-dimethylbenz(a)anthracene to
Sprague-Davley rats resulted in the production of mammary cancer or
fibroadenoaas in 100% of the treated animals. Huggins (1965) later reported
that intragastric feeding of 7,12-dimethylbenz(a)anthracene to Sprague-Davley
rats could be substituted vith a single intravenous injection of 5 mg 7,12-
diaethylbenz(a)anthracene for the purpose of inducing mammary cancer. By this
technique, Huggins successfully produced mammary carcinomas in all of 1500
Sprague-Davley rats treated ac age 50 days. Tumors were detected by palpation
as early as 20 days after 7,12-dimethylbenz(a)anthracene injection. Medina et
al. (1980) shoved a 50% tumor incidence reached after 34 veeks, vith 70% of
the tumors being adenocarcinemas, in female C57BL/6x, UBA/2fFl mice vhen given
1-1
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ar. incragastric feeding of 7,12-dinethylbenz(a)anthracene of 1.0 ng once/veek.
In another study (Yoshida and Fukunishi, 1977), mammary adenocarcinoaas and
leukemia developed in male Sprague-Davley rats treated intragastrically with
7,12-dimethyIbenz(a)anthracene. It is now known that 7,12-dimethylbenz(a)-
anthracene can also produce tumors in the mammary gland, ovaries, and pancreas
of rats by direct local application to the target organ (Sinha and Dao, 1974;
Kato et al., 1975; Satake et al.. 1975). By direct application, mammary
adenocarcinomas could be produced with single doses of 7.12-dimethyIbenz-
(a)anthracene as low as 300 ug (Sinha and Dao. 1974).
1.2 HUMAN STUDIES
Pertinent data regarding the effects of human exposure to 7.12-dimethylbenz(a)-
anthracene were not located in the available literature.
1.3 UEIGHT-OF-EV1DENCE ASSESSMENT
Studies with experimental animals of several species exposed to 7.12-dimethyl-
benz(a)anthracene by various routes provide unequivocal evidence that the
substance is an animal carcinogen. Single doses of 7,12-dimethylbenz(a)anthra-
cene. often in sicrograa quantities, are generally sufficient to Induce tunor
formation. 7,12-Dimethylbenz(a)anthracene is most often used for the induction
of experimental tumors and as a model compound for studying the mechanism of
action of carcinogens. Because of its high carcinogenic potency in animals.
chronic exposures are not necessary to demonstrate the tumorigenic activity;
thus, published studies Involving long-term exposure to 7.12-dimethylbenz(a)-
anthracene are not available. This situation complicates any attempt to
calculate • carcinogenic potency factor (F) for 7,12-dlaethyIbenz(a)anthracene.
A human population has not been identified which is exposed to 7.12-dimethy1-
benz(a)anthracene In either the community or the workplace. Thus, using the
EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA. 19B6a) for evaluating
the overall weight of evidence to humans, 7.12-dimethyIbenz(«)anthracene is
most appropriately classified as a Croup 12 chemical. The appendix contains
summaries of the significant human and/or animal studies cited in this review.
1-2
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2.0 POTENCY
The potency factor (F) for 7,12-dinethylbenz(a)anthracene is estimated to be
540 (ag/kg/day)~l. placing it in potency group 1 under the CAC's methodology
for evaluating potential carcinogens (U.S. EPA, 1986b). Table 2-1 contains
data froa the selected study used to derive the potency factor (F) for
2-1
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Table 2-1. Derivation of Potency Factor(F)
Agent: 7.12-Bfmcthylbefuialanthrmcene
REFERENCE:
EXPOSURE ROUTE:
SPECIES:
STRAIN:
SEX:
VEHICLE OR PHYSICAL STATE:
BOOT WEIGHT:*
DURATION Of TREATMENT:
DURATION OF STUDY:
LIFESPAN OF ANIMAL:*
TARGET ORGAN:
TUMOR TYPE:
EXPERIMENTAL DOSES/
EXPOSURE:
, TRANSFORMED DOSES:
p (mg/kg/day)
TUMOR INCIDENCE:
ANIMAL POTENCY:
(mg/kg/day)"1
NUNAN POTENCY:0
(Mg/kg/day)'1
.b
Medina et •!.. 1980
intragastric
mice
BD2FT
F
cottonseed oil
0.03 kg
6 week* (42 day*)
730 day*
730 day*
breast
adenoc arc < noma/ adanocanthoM
1.0 mg
0.27
24/35
40.69
540
0.0 Mg
0.0
0/43
• Estimated
b To derive the transformed dose fro* the experimental dose data: experimental do*e (tag)/ animal's weight (kg) x 1 (treatment dey/wcek)/
7 (days/Meek) K duration of treatment (days)/duration of study (days).
c Human potency • anisMi potency x (70kg/0.03kg)
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3.0 HAZARD RANKING
Based on che weight-of-evidence Group B2 for 7,12-Dimethylbenz(a)anthrene and
me pocency faccor (F) of 540 (Kg/kg/day). 7,12-diaechylbenz(a)anthrene
receives a hazard ranking of "HIGH."
3-1
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4.0 REFERENCES
Albert, R.E.. F.J. Burns and B. Alcshuler, 1978. Temporal Aspects of
Tuaorigenic Response to Individual and Mixed Carcinogens. Comprehensive
Progress Report. Institute of Environ. Med.. New York Univ. Med. Center. New
York. SY. 1C016.
Seattle. E.J.. E.V. Staub. N. Correll and G. Mass, 1961. Bronchogenic
Carcinoaa Produced Experimentally in the Dog. J. Thorac. Cardiovasc. Surg.
42: 615-622.
Berenblun. I.. 1949. The Carcinogenic Action of 9.10-Di«ethyl-l(2-Benzanthra-
cene on the Skin and the Subcutaneous Tissues of the Mouse. Rabbit, Rat and
Guinea Pig. J. Natl. Cancer Inst. 10: 167-175.
Buu-hoi. N.P.. 1964. New Developments in Chealcal Carcinogenesis by Polycyclic
Hydrocarbons and Related Heterocycles: A Review. Cancer Res. 24(9): 1511-1523.
Dao, T.L.. 1964. Carcinogenesis of Maanary Gland in Rat. Prog. Exptl. Tumor
Res. 5: 157-216.
Delia Porta. G.. L. Kolb and P. Shubik. 1958. Induction of Tracheobroncial
Carcinonas in the Syrian Golden Haaster. Cancer Res. 18: 592-597.
Edgcoab. J.H. and H. Mitchelich. 1962. Melanonas of the Skin of Guinea Pigs
Following the Application of a Solution of 9.10-Diaethyl-l,2-Benzanthracene in
Benzene. Acta Un. Inc. Cancer. 19: 706-707.
Flesher. J.W.. R.G. Harvey and K.L. Sydnor, 1976. Oncogenlcity of K-Region
Epoxides of Benzo(a)pyrene and 7,12-Dimethylbenz(a)anthracene. Int. J. Cancer.
18: 351-353.
4-1
-------
Grisvold, D.P., H.E. Skipper, U.R. Laster, U.S. Wilcox and F. Schabel, 1966.
Induced Mammary Cancer in the Female Rat as a Drug Evaluation System. Cancer
Res. 26: 2169.
Grube, D.D.. C. Peraino end R.J.M. Fry, 1975. The Effect of Dietary Phenobar-
bital on the Induction of Skin Tumors in Hairless Mice with 7.12-Dimethylbenz-
(a)anthracene. J. Invest. Dermatol. 64: 258-262.
Hovell. J.S., 1962. Skin Tumors in the Rat Produced by 9.10-Dimethyl-
1,2-Benzanthracene and Methylcholanthrene. Brit. J. Cancer. 16: 101-109.
Huggins, C., R.C. Moon and S. Morii. 1962. Extinction of Experimental Mammary
Cancer. I. Estradiol-17B and Progesterone. Proc. Natl. Acad. Sci., USA. 48:
379.
Huggins. C., 1965. Two Principles in Endocrine Therapy of Cancers: Hormone
Deprival and Hormone Interference. Cancer Res. 25: 1163.
Kato. T.. M. Yakushifi. A. Tsunavaki. et al.. 1975. Studies on Experimental
Formation of Ovarian Tumors - Especially the Discussion of the Developing
Process of Ovarian Tumors Following an Application of DMBA. Kurume Med. J.
22(3): 169-176.
Klein. M.. 1956. Induction of Skin Tumors in the Mouse with Minute Doses of
9,10-Dimethyl-1.2-Benzanthracene Alone or with Croton Oil. Cancer Res. 16:
123-127.
Law, L.V.. 1941. Multiple Skin Tumors in Mice Following a Single Painting with
9.10-Dimethyl-l,2-Benzanthracene. Am. J. Pathol. 17: 827-831.
Medina. D.. J.S. But«l. S.H. Soch«r and F.L. Miller. 1980. Mammary Tumori-
genesis in 7.12-Dimethylbenzanthracene-Treated C57BL x DBA/2f Fl Mice. Cancer
Res. 40(2): 368-373.
4-2
-------
Paiadugu. R.R., E.G. Shors. A.H. Cohen, K. Matsumura and J.R. Benfield, 1980.
Induction of Lung Cancers in Preselected. Localized Sites in the Dog. J. Natl.
Cancer Inst. 65: 921-927.
Pawlowski, A., H.F. Habernan and I.A. Menon, 1976. Junctional and Compound
Figmented Nevi Induced by 9,10-Dimethyl-l,2-Benzanthracene in Skin of Albino
Guinea Pigs. Cancer Res. 36: 2813-2821.
Pearson. O.H.. 1973. Animal Models of Endocrine-Related Cancer. In: Host
Environment Interactions in the Etiology of Cancer in Han. Proc. of a Meeting.
Primosten, Yugoslavia. August 27-September 2. 1972. Lyon. France, IARC. 1ARC
Publ. No. 7. pp. 137-141.
Roe. F.J.. 1956. The Development of Malignant Tumors of Mouse Skin After
Initiating and Promoting Stimuli. 1. The Effect of a Single Application of
9.10-Dimethyl-l,2-Benzanthracene (DMBA), with and without Subsequent Treatment
vich Croton Oil. Brit. J. Cancer. 10: 61-69.
Satake. K.. K. Umeyaoa. K. Kamino. K. Uchiaa, K. Yamashita and S. Yamamoto.
1975. Pancreatic Cancer Developing in Sprague-Davley Rats After Local
Application of 7.12-Dimethylbenzanthracene (DMBA). Osaka City Med. J. 21(2):
119-125.
Sinha. D. and T.L. Dao., 1974. A Direct Mechanism of Mammary Carcinogenesis
Induced by 7.12-Diaethylbenz(a)anthracene. J. Natl. Cancer Inst. 53(3):
841-846.
Slaga. T.J., G.T. Bovden, J.D. Schribner and R.K. Boutwell, 1974. Dose-Response
Studies on the Ability of 7,12-Dimethylbenz(a)anthracene and Ben±(a)anthracene
to Initiate Skin Tumors. J. Natl. Cancer Inst. 53(5).
Staub, E.U., R. Eisenstein, G. Has* and E.J. Beattie. 1965. Bronchogenic
Carcinoma Produced Experimentally in the Normal Dog. J. Thorac. Cardiovasc.
Surg. 49: 364-372.
4-3
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Terracini. B., P. Shubilc and G. Delia Porta. 1960. A Study of Skin Carcino-
genesis in the Mouse with Single Applications of 9,10-Demethyl-l,2-Benzanthra-
cene at Different Dosages. Cancer Res. 20: 1538-1542.
U.S. EPA (Environmental Protection Agency), 1986a. Guidelines for Carcinogen
Risk Assessment, 51 £R 33992-34003, September 24, 1986.
U.S. EPA (Environmental Protection Agency), 1986b. Methodology for Evaluating
Potential Carcinogenicity in Support of Reportable Quantity Adjustments
Pursuant to CERCLA Section 102, OHEA-C-073, December 1986. Available from
CERCLA Docket 102RQ-273C. The public document for RQ rulemaking is located in
room M2427, U.S. Environmental Protection Agency, 401 M Street, SW, Washington,
DC 20460. It is available for inspection Monday through Friday excluding
Federal holidays, between the hours of 9:00 a.m. and 4:00 p.m.
U.S. EPA (Environmental Protection Agency), 1988. Technical Background
Document to Support Rulemaking Pursuant to CERCLA Section 102, Volume 3, Draft,
Appendix A, April 26, 1988.
Yoshida, H. and R. Fukunishi, 1977. Mammary Tumor and Leukemia in Male
Sprague-Davley Rats Evolved by a Series of Intragastric Administration of
7.12-Dimethylbenz(a)anthrac:ne. Gann. 68: 237-239.
4-4
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APPENDIX
SUMMARY OF SIGBITICANT HUMAH AND/OR ANIMAL STUDIES
A-1
-------
Table A. Animal
Agent: 7,12-Dimethyl bent(a)anthracene
• Reference: Grube et el., 1975
Exposure
•out*
•Ba»BBBMm»BBN«mM
d
d
MA
Specie*/
Strain
•^^•••MM^BWMMMM
•lee/
NSR/J
•ice/
NSR/J
•tee/
NSR/J
Dote
or
Sex Exposure
••^••••^•••^••^•••••••^••M^mi
r too ug
once/Meek
F 250 ug
once/week
f untreated
Duration
of
Treatment
M^M^^MBIBB^^HMMIM
12 weeks
12 Meoks
NA
Duration
of
Study
^^••••^•V^^BMMMI
40 weeks
40 weeks
life
Purity
of
Compound
•^••MM^HMVIBIM^^BB*
HR
NR
NA
Vehicle or
Physical Target
State Organ
^^•«H^.WM^W«*mHBM«^MWM^^HMB^^
acetone skin
(0.1 Ml)
acetone skin
(0.1 •!>
NA skin
Tumor Type
peplllosis/
sarcona/
eorclnoM
papi Home/
sarcoM/
carcinoma
papllloma/
f ibrosarcore
Tumor
Incidence
(P value)
28/29* -b
30/30*'6
2/76
OUALITT Of EVIDENCE
StrengtM of Study: Relatively extended duration of exposure; hlatopathology performed on some animals; good reporting of
data.
Weaknesses of Study: Rout* of exposure may be considered environmentally Irrelevant.
Overall Adequacy: Adequate
• Animals Mere 10-12 weeks of age at start of study and Mere fed SOX casein pelleted diet throughout the experiment.
b Total number of carcinomas Mas IS; final Incidence was 13*.
c Alt animals have multiple paptHomes and lesions that appeared to b* malignant by the 15th Meek and the experiments Mere
terminated. No hletopathologic examination Mas carried out.
MA • Not applicable; NR • Not reported
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table A. Animal
Agentt 7,t2-Oimethytbenzlalanthracene
Reference! Nidlna et el., 1980
Exposure
•out*
It
Species/
Strain
•tct/
CSm/6»
OIA/2fM
Dose Duration Duration
or of of
Son Exposure Treetawnt Study
f 1.0 *g A nooks lifetlaw
onco/Mook
bealnnlnt
at ft wooka
Of OflO
Purity Vehicle or
of Physical Target
CoMpound State Organ
MR 1.0 «g breaat
ditaotved
in 0.2 •(
cottonaaed
oil
Tunor
Incidence
TuMor Type (P value)
adenocarclnona 24/J5*'b
adenocanthoiia
•Ice/
csm/ox
untreated
KfetlM
NA
NA
breaat
NA
0/43
QUALITY Of EVIDENCE
of ttudyi Excellent reportint of data; hlatopathologlc eKMinationa conducted; aniauila observed for life.
Ueakneaaaa of Study: Halted duration of exposure; tuaor incidence data reported only for breast.
Overall Adequacy: Adequate
• SOX tuawr incidence not reached at M weeka. Mean ege of alee dying without tuaoi a Mas 43 weeks.
b 70S of tuaora were adenocarclnoMs.
MA • Mot applicable; MR • Nat reported
-------
Table A. Animal
Agenti 7,12-Dimethylb«ns(a)anthracene
Reference: Staub tt el., 1965
txpoaure
loutt
It
Specie*/
. Strain
dog/
mongrel
Dot*
or
Sex Expotur*
N.r 2 «a
once/Meek
Duration
of
Treatment
up to 63
weeke
Duration
of
Study
1V-JZ
month*
.
Purity
of
Compound
MR
VchtcU or
Physical
Stato
IX in
gelatin
•uapan* f on
Target
Organ Tumor Type
lung carcinoma
Tumor
Incidence
(P value)
3/U-
NA
dog/
NR
MR untreated
1A
NR
NA
lung
carcinoma
15/928Zb
MJALITT OF EVIDEICE
Strength* of Studyt Repeated eitpoture regtaen; good reporting of data; Matopathologlc emmlnatlon* perforated.
Ueakneaae* of Studyi larly death aajong aeverat animal*; no concurrent control group.
Overall Adequacy: Adequate
1 Carcinoma developed In animal* treated for 55-58 Meek* tilth OMBA. Ten of the 14 dog* died Mlth an ulceratlve trachaobroncho-
pneumonia; 8 of the dogs survived for >1 year.
b Historical nacropay data citad by the authors.
MA • Mot applicable; NR • Mot reported
-------
laoirflr
Animal
Agent: 7.12-Dlmethylbeni(a)anthracene
References Yoshtda and fukunlshi,
Exposure
Route
<9
Species/
Strain
ret/
Sprague-
Dauley
Oo»e Duration Duration
or of of
Sex Exposure Treata>ent Study
M 6 doses of 16 weeks 200 days
10 Hfl each
at biweekly
Intervals
(total dose*
60 ng)
Purity Vehicle or
of Physical Target
Compound State Organ Timor Type
NR O.SX in MMaary adenocarcinowa
sesasie oil gland.
heeiatopoletic leukemia
systeei
TuMor
Incidence
(P velue)
85/164*
51/164*
OUOtlTT Of IVIOEelCe
Strengths of Study: Large nuefcer of anlatals, ewitiple doses administered. Itistopathologlc «x««lnations perfcrowd.
Uee.kne.ates of Study: Mo control group
Overall Adequacy: I tested
* U7 of the 311 rata died during the treatawnt period end Merc ellsilneted froei the study.
MR • Not reported
-------
ND
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