Environment and Breast Cancer: Science Review

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Key References
Abbreviations
 

benzene
CAS RN 71-43-2

Chemical Summary
Exposure and Risk Assessment
Cancer Studies
 


Cancer studies: Mammary gland tumors
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Originating list
The list(s) or database(s) in which the chemical was identified as showing an increase in mammary gland tumors. CPDB: Carcinogenic Potency Database, IARC: International Agency for Research on Chemicals Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man summaries, NTP TR: National Toxicology Program (NTP) Technical Reports, NTP 11ROC: NTP 11th Report on Carcinogens, CCRIS: Chemical Carcinogenesis Research Information Service.
Carcinogenicity Potency Database, National Toxicology Program studies, Chemical Carcinogenesis Research Information System
Mammary gland tumor summary
A summary of findings related to mammary gland tumors, most often excerpted from IARC Monographs or the NTP 11th ROC, and, in some cases, supplemented by our evaluation of individual studies and reviews, is available for the priority chemicals and 67 others.
Four studies noted mammary tumor increases due to treatment. Some studies that did not show an increase in mammary tumors used only male animals. NTP 11th ROC: When administered orally, benzene caused mammary-gland carcinoma and carcinosarcomas in female mice.
Citations to review sources and individual studies reporting mammary gland tumors are listed below.
Citation
Source Type
Notes
International Agency for Research on Cancer, Monographs on the evaluation of carcinogenic risk of chemicals to man. VOL.: 29 (1982) (p. 93) Benzene.
Review
oral treatment in rats increased mammary tumors: Maltoni and Scarnato 1979
http://monographs.iarc.fr/ENG/Monographs/vol29/volume29.p...
International Agency for Research on Cancer, Monographs on the evaluation of carcinogenic risk of chemicals to man.Supplement 7: (1987) (p. 120) Benzene.
Review
"Following its oral administration at several dose levels, it induced neoplasms at multiple sites in males and females of both species" ref IARC v.29 1982, Maltoni 1982, 1983, 1985. "Exposure of rats by inhalation increased the incidence of neoplasms, mainly carcinomas, at various sites." Maltoni 1983, Maltoni 1985, Maltoni 1982b, Maltoni 1982c, Snyder 1980
http://monographs.iarc.fr/ENG/Monographs/suppl7/suppl7.pd...
Carcinogenic Potency Database 2005. Gold LS ST, Manley NB, Garfinkel GB, Ames BN. Summary Table by Chemical of Carcinogenicity Results in CPDB on 1485 Chemicals. 2005
Review
4 of 6 studies reported mammary tumors: NTP TR289, Maltoni 1988, Maltoni 1985, Snyder 1984. Studies that did not report mammary tumors were Snyder 1978 and 1980.
http://potency.berkeley.edu/pdfs/ChemicalTable.pdfpotency...
National Toxicology Program 11th Report on Carcinogens
Review
by oral ,increased mammary tumors in female rats - NTP TR289
http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s019be...
Maltoni C, Conti B, Cotti G, Belpoggi F. Experimental studies on benzene carcinogenicity at the Bologna Institute of Oncology: current results and ongoing research. Am J Ind Med 1985;7(5-6):415-46
Primary Literature

experimental details
Numbers seem to show only a marginal increase in mammary tumors. 1st experiment: female rats 4/30, 4/30, 7/35 (or numbers corrected for number of animals alive when first tumor of this type was detected: 4/30, 4/28, 7/28) 2nd experiment: female rats 7/50, 7/40 (or corrected numbers 7/49, 7/40) 3rd experiment: breeders 2/60, 6/54 (corrected is same), embryos are same as controls
Maltoni C, Conti B, Perino G, Di Maio V. Further evidence of benzene carcinogenicity. Results on Wistar rats and Swiss mice treated by ingestion. Ann N Y Acad Sci 1988;534:412-26.
Primary Literature

experimental details
Increases malignant mammary tumors in female mice. 0, 500 mg/kg, 1/day, 4-5days/wk for78 wks, female mice: 2/40, 19/40 carcinoma.
National Toxicology Program Technical Report 289, 1986.
Primary Literature

experimental details
Increased malignant mammary tumors seen in female mice, not rats. female rats and mice: 0, 25, 50, 100 mg/kg body weight; 5 days/wk for 103 weeks; female mice: 0/49, 2/45, 5/50, 10/49 carcinoma female mice: 0/49, 0/45, 1/50, 4/49 carcinosarcoma
http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr289.pdf
Snyder CA, Goldstein BD, Sellakumar AR, Albert RE. Evidence for hematotoxicity and tumorigenesis in rats exposed to 100 ppm benzene. Am J Ind Med 1984;5(6):429-34.
Primary Literature

experimental details
One malignant mammary tumor occurred in a a male rat, and no female animals were used. Also used lower levels of benzene than other studies.
Snyder CA, Goldstein BD, Sellakumar AR, Bromberg I, Laskin S, Albert RE. The inhalation toxicology of benzene: incidence of hematopoietic neoplasms and hematotoxicity in ARK/J and C57BL/6J mice. Toxicol Appl Pharmacol 1980;54(2):323-31
Primary Literature
A study listed by CPDB 2005 that did not report mammary tumors. Only male animals and appears to have a blood focus.
Synder CA, Goldstein BD, Sellakumar A, Wolman SR, Bromberg I, Erlichman MN, et al. Hematotoxicity of inhaled benzene to Sprague-Dawley rats and AKR mice at 300 ppm. J Toxicol Environ Health 1978;4(4):605-18.
Primary Literature
A study listed by CPDB 2005 that did not report mammary tumors. Only male animals and blood focus.
Maltoni C, Conti B, Cotti G. Benzene: a multipotential carcinogen. Results of long-term bioassays performed at the Bologna Institute of Oncology. Am J Ind Med 1983;4(5):589-630.
Primary Literature
From IARC, review postponed.
Maltoni C, Conti B, Scarnato C. Squamous cell carcinomas of the oral cavity in Sprague-Dawley rats, following exposure to benzene by ingestion. First experimental demonstration. Med Lav 1982;73(4):441-5.
Primary Literature
From IARC, review postponed.
Maltoni C, Cotti G, Valgimigli L, Mandrioli A. Hepatocarcinomas in Sprague-Dawley rats, following exposure to benzene by inhalation. First experimental demonstration. Med Lav 1982c;73(4):446-50.
Primary Literature
From IARC, review postponed.
Maltoni C, Cotti G, Valgimigli L, Mandrioli A. Zymbal gland carcinomas in rats following exposure to benzene by inhalation. Am J Ind Med 1982b;3(1):11-6.
Primary Literature
From IARC, review postponed.
Maltoni C, Scarnato C. Health Hazard Evaluation Determination Report No 78-57-579. Texas City Tx: Amoco Texas Refining Company; 1979
Primary Literature
From IARC, review postponed.