Environment and Breast Cancer: Science Review


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n-nitroso-di-n-butylamine
CAS RN 924-16-3



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.
Industrial chemical
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Found in consumer products
"Likely" indicates that the chemical is contained in consumer products or traces of the chemical are present in products, including food and water, resulting in likely exposure for the general population. For some chemicals marked as "likely," consumer product uses have been discontinued, and this will be indicated in the "Use in Consumer Products" field.
Likely
Food additive in US
Chemicals are classified as "Listed" or "Not listed" in the Everything Added to Food in the United States database developed by the US Food and Drug Administration.(22)
Not listed
California Proposition 65
Chemicals are labeled "Listed" or "Not listed" based on the Proposition 65 list of chemicals updated on May 27, 2005. Listed chemicals are "chemicals known by the State of California to cause cancer or reproductive toxicity"(19).
Listed
Air pollutant
Chemicals classified as "Likely" air pollutants are those likely to be found in indoor or outdoor air, including products of combustion and industrial chemicals that may offgas from consumer products, leading to human exposure.
Likely
Current High Production Volume chemical
Chemicals are classified "Yes" or "No," based on 2002 production volume information submitted to the US EPA: "Yes" for >1 million pounds produced; "No" for < 1 million pounds produced. Some past production volumes are referenced, where appropriate, in the HPV comment column (20). In addition, Scorecard.org is referenced and noted in the HPV comment column when it was inconsistent with current production volume information obtained from US EPA (21).
No
Production volume information
Production volume information is from the US EPA database on non-confidential production volume information submitted by companies for chemicals under the 1986-2002 Inventory Update Rule (IUR) using the most updated (2002) values (20). The Inventory Update Rule requires the submission of basic production data every four years on chemical substances manufactured (including imported) for commercial purposes in amounts of 25,000 pounds or more at a single site. Out of over 80,000 chemicals on the TSCA Chemical Substances Inventory, reports are required for approximately 9,000 substances. For those substances with annual volumes of 300,000 lbs or more per site, reporters also submit chemical processing and use information.
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General population exposure
This field includes information describing pathways of exposure for the general population obtained from a variety of sources including: IARC Monographs (9), NTP 11th ROC on Carcinogens (4), NTP Study Reports and Abstracts (3), Hazardous Substance Database (10), and other sources located through use of the Google search engine.
The general population may be exposed sporadically to low levels of N-nitrosodi-n-butylamine (IARC 1978 vol.:17 p.51). Estimates indicate that air, diet, and smoking contribute to potential human exposure at levels of a few µg per day. N-Nitrosamines, such as N-nitrosodi-n-butylamine, are frequently produced during rubber processing and may be present as contaminants in the final rubber product. The U.S. Consumer Product Safety Commission (CPSC) and FDA determined that the nitrosamines present in pacifiers and baby bottle nipples can migrate from the pacifier or nipple into saliva, which could result in ingestion of nitrosamines (11th ROC). Humans may be exposed from ingesting foods that contain the chemical, from rubber nipples of baby pacifiers, from cigarette smoke, and from breathing the air inside new cars (HSDB).
Use in consumer products
Summaries of chemical use in consumer products were developed from information found in US EPA SRD (11), NLM HPD (12), and Scorecard (12). Major uses were taken from IARC Monographs (9), NTP 11th ROC (4), NTP Study Reports (3), HSDB (10), and 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.
No consumer products listed in SRD, HPD, or Scorecard. Used primarily as a research chemical. It has also been used as an intermediate in the synthesis of di-n-butylhydrazine, and has been tested for fungistatic activity. Not currently commercially produced in the US. N-Nitrosodi-n-butylamine has been detected in a variety of products as a result of the nitrosation of amines present in these products. N-Nitrosodi-n-butylamine is present in soybean oil at a concentration of 290 µg/kg, in cheese at 20 to 30 µg/kg, and in smoked or cured meats at 0.2 to 3.9 µg/kg. N-Nitrosodi-n-butylamine has also been detected in tobacco smoke at a concentration of 3 ng/cigarette (11th ROC). Has been found in cooked fish, pork luncheon meat, the interior of new cars, cigarette smoke, and an aqueous rubber extract (HSDB).
Occupational exposure to women
We extracted the total number of potentially exposed workers and the number of potentially exposed female workers from the National Occupational Exposure Survey (NOES) 1981-1983; we listed specific industry classifications if >5,000 women were potentially exposed in that industry. Note: NOES does not include farm workers.
Not listed in NOES. Researchers engaged in studying the biological effects of N-nitrosodi-n-butylamine may possibly be exposed to this compound in the workplace (11th ROC).
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).
B2: Probably Carcinogenic to Humans, inadequate evidence
US EPA Weight of Evidence narrative
US EPA narrative statement of overall weight of evidence for carcinogenicity (animal, human, and other supportive data).
Increased incidences of several tumor types in rats, mice, and hamsters exposed by various routes.
US EPA slope factor basis
Lists target organs used for estimating carcinogenic potency of the chemical (17).
Oral, Inhalation: Bladder and esophagus tumors-male mouse
NIOSH Pocket Guide - potential carcinogen?
This field indicates whether NIOSH identifies the chemical as a potential carcinogen for workers (yes/no) (24).
NA
NIOSH Pocket Guide - cancer sites
Lists target organs from animal cancer bioassays (24).
NA
Risk assessments not reviewed for this chemical