Abstract:
BACKGROUND:Due to the large number of chemicals not yet tested for carcinogenicity but to which people are exposed, the limited number of human and animal cancer studies conducted each year, and the frequent need for a timely response, mechanistic data are playing an increasingly important role in carcinogen hazard identification. OBJECTIVES:To provide a targeted approach to identify relevant mechanistic data in our cancer evaluation of haloacetic acids (HAAs), we used several approaches including systematic review, the 10 key characteristics of carcinogens (KCs), and read-across methods. Our objective in this commentary is to discuss the strengths, limitations, and challenges of these approaches in a cancer hazard assessment. METHODS:A cancer hazard assessment for 13 HAAs found as water disinfection by-products was conducted. Literature searches for mechanistic studies focused on the KCs and individual HAAs. Studies were screened for relevance and categorized by KCs and other relevant data, including chemical properties, toxicokinetics, and biological effects other than KCs. Mechanistic data were organized using the KCs, and strength of evidence was evaluated; this information informed potential modes of action (MOAs) and read-across-like approaches. Three read-across options were considered: evaluating HAAs as a class, as subclass(es), or as individual HAAs (analog approach). DISCUSSION:Because of data limitations and uncertainties, listing as a class or subclass(es) was ruled out, and an analog approach was used. Two brominated HAAs were identified as target (untested) chemicals based on their metabolism and similarity to source (tested) chemicals. In addition, four HAAs with animal cancer data had sufficient evidence for potential listing in the Report on Carcinogens (RoC). This is the first time that the KCs and other relevant data, in combination with read-across principles, were used to support a recommendation to list chemicals in the RoC that did not have animal cancer data. https://doi.org/10.1289/EHP5672.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Atwood ST,Lunn RM,Garner SC,Jahnke GDdoi
10.1289/EHP5672subject
Has Abstractpub_date
2019-12-01 00:00:00pages
125003issue
12eissn
0091-6765issn
1552-9924journal_volume
127pub_type
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.7827261
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journal_title:Environmental health perspectives
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pub_type: 杂志文章,随机对照试验
doi:10.1289/ehp.1103898
更新日期:2012-03-01 00:00:00
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journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP5862
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journal_title:Environmental health perspectives
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更新日期:1998-04-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1289/ehp.1104327
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pub_type: 杂志文章,评审
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pub_type: 临床试验,杂志文章
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doi:10.1289/ehp.85-1568331
更新日期:1990-04-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.00108709
更新日期:2000-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.7929105
更新日期:1979-04-01 00:00:00
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doi:10.1289/EHP1910
更新日期:2017-11-20 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.8562177
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更新日期:2019-10-01 00:00:00
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更新日期:2017-11-07 00:00:00