Environment and Breast Cancer: Science Review


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thiotepa
CAS RN 52-24-4



Originating list
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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.
IARC Monographs, National Toxicology Program studies, National Toxicology Program 11th Report on Carcinogens, Chemical Carcinogenesis Research Information System
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Associated chemicals
Names of closely related chemicals discussed in the "originating list" are listed here if they were not separately reviewed.
none
Major use
We assigned each chemical into one of the following groups based on its major sources and uses: industrial chemicals, chlorinated solvents, products of combustion, pesticides, dyes, radiation and drinking water disinfection, pharmaceuticals, hormones, natural products, and research chemicals.
Pharmaceutical
Widespread exposure
If a chemical is a High Production Volume chemical, added to food, found in air pollution or consumer products, or causes greater than 5000 women to be exposed occupationally, it was judged to cause a likely widespread exposure to women in the United States.
More Likely
Human exposure summary
Information describing pathways of exposure for the general population was obtained from a variety of sources, including IARC Monographs (9), NTP 11th ROC (4), NTP Study Reports (3), and Hazardous Substance Database (10). Summaries of chemical use in consumer products were developed from information found in US EPA's Source Ranking Database (SRD) (11), the NLM Household Product Database (HPD)(12), Scorecard (12), and Pesticide Action Network (PAN) Pesticides Database (13). If a chemical could not be found in these sources, we searched ToxNet (14), PubChem (15), and The Merck Index (16), and conducted searches by both name and CAS No. using Google.
Used in cancer therapy (NTP 11th ROC).
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.
NTP 11ROC: In rats, intraperitoneal injection of thiotepa caused malignant mammary tumors in females. Malignant mammary gland tumors were significantly increased in the NTP study, however the study authors come to conflicting conclusions as to whether the increase is related to administration of thiotepa. This finding does not appear in the study abstract.
International Agency for Research on Cancer evaluation
IARC classification
Overall evaluation: Group 1: The agent is carcinogenic to humans. Group 2A: The agent is probably carcinogenic to humans. Group 2B: The agent is possibly carcinogenic to humans. Group 3: The agent is not classifiable as to carcinogenicity in humans. Group 4: The agent is probably not carcinogenic to humans. NA: not evaluated by IARC (9).
1: Carcinogenic to humans
Evidence in humans
Strength of the evidence in humans (summary of epidemiologic evidence) and animals: sufficient, limited, or inadequate. If IARC has not reviewed the chemical, this field will be labeled "NA".
sufficient
Tumor sites identified in IARC Monographs
If tumors were found in humans, the entry in this field will be labeled "(human)." Unlabeled terms are from animal studies. Tumor sites are abbreviated and can be referenced in the key (Table 1). NA: not evaluated by IARC.
leukemia (human), lung, lymphatic system, uterus, mammary gland
Evidence in animals
Strength of the evidence in humans (summary of epidemiologic evidence) and animals: sufficient, limited, or inadequate. If IARC has not reviewed the chemical, this field will be labeled "NA".
sufficient
US EPA cancer classification
The US EPA Weight of Evidence Characterization of the chemical’s carcinogenic potential is listed: Group A: Carcinogenic to humans; Group B: Probably carcinogenic to humans. Group C: Possibly carcinogenic to humans. Group D: Not classifiable as to human carcinogenicity. Group E: Evidence of non-carcinogenicity for humans. NA: Not evaluated by US EPA (17).
NA
National Toxicology Program Study Conclusions
The National Toxicology Program Technical Reports include a determination of the carcinogenicity of the test chemical in each sex and species tested. Designations prior to 1983 are "positive" or "negative". After 1983, NTP assigned designations of "clear evidence of carcinogenicity," "some evidence of carcinogenicity," "equivocal evidence of carcinogenicity," "no evidence of carcinogenicity," or "inadequate study of carcinogenicity." The words "of carcinogenicity” are removed from the field in this database to conserve space. "NA" indicates no NTP technical report for the chemical (3).
Female rats
Positive
Female mice
Positive
Male rats
Positive
Male mice
Positive
Mutagenicity from CPDB
This summary of evidence from the Carcinogenic Potency Database is labeled “Yes” if the agent is mutagenic or weakly mutagenic in the Salmonella assay and “No” if not. NA: Not listed in CPDB. NA-S: Listed in CPDB, but no assessment of mutagenicity in Salmonella is included (1).
Mutagenic
Mutagenicity from RTECS
This summary of evidence from the Registry of Toxic Effects of Chemical Substances database (NIOSH 2005) is labeled “Yes” if the agent is listed as mutagenic, “No” if not. NA: Not listed in RTECS (18).
Mutagenic