Epidemiology of lung cancer among acrylonitrile-exposed study populations: A meta-analysis

Alexander, Dominik D.; Pastula, Susan T.; Riordan, Alexander S

doi:10.1016/j.yrtph.2021.104896

Cited by 4 publications

(6 citation statements)

References 25 publications

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“…82 Dose-related covalent binding of CEO to DNA with formation of N7-(2-oxoethyl) guanine (N7-OEG) adducts was also observed in human TK6 lymphoblastoid cells following 2-hour incubation with 35 or 105 μ m [2,3– 14 C]-CEO and in DNA extracted from brains and livers of control F344 rats and incubated with 1.07, 5.33, and 53.5 μ m of CEO for 8 hours. 22 Several other studies reported acrylonitrile binding to DNA in vitro , with N7-OEG being the major acrylonitrile-specific adduct, in addition, 1,N 6 -ethenodeoxyadenisune and 3,N4-ethenodeoxycytidine are among the most commonly observed adducts. 82,113–115 However, the sensitivity of these studies was limited, since they used low specific activity 14 C-acrylonitrile in conjunction with liquid scintillation counting.…”

Section: Resultsmentioning

confidence: 98%

“…5–12 While a recent retrospective study by the US National Cancer Institute on mortality of workers exposed to acrylonitrile reported a statistically significant ( p for trend = .05) association between acrylonitrile exposure and lung cancer, as well as a possible association with increased mortality from bladder cancer and pneumonitis, 35 findings from comprehensive meta-analysis did not support increased risk of lung cancer among acrylonitrile-exposed workers. 4…”

Section: Resultsmentioning

confidence: 99%

“…[5][6][7][8][9][10][11][12] While a recent retrospective study by the US National Cancer Institute on mortality of workers exposed to acrylonitrile reported a statistically significant (p for trend = .05) association between acrylonitrile exposure and lung cancer, as well as a possible association with increased mortality from bladder cancer and pneumonitis, 35 findings from comprehensive meta-analysis did not support increased risk of lung cancer among acrylonitrile-exposed workers. 4 The International Agency for Research on Cancer (IARC) conducted several evaluations of acrylonitrile. In the first evaluation, IARC concluded that acrylonitrile "should be regarded as if it was carcinogenic to humans."…”

Section: Summary Of Acrylonitrile Toxicity and Carcinogenicity In Humansmentioning

confidence: 99%

“…15,16 In humans, while some studies detected an association between acrylonitrile exposure and increased risk of lung cancer in humans, 35 others have shown that these findings are unsupported based on the absence of dose-response and lack of proper adjustments for confounding factors, such as smoking. 4 Currently, the occupational exposure levels to acrylonitrile are estimated to be below 2 ppm. 7,28 Assuming that the highest allowed occupational exposure to acrylonitrile is 2 ppm or 4.3 mg/m 3 for 8-hours over a 40-hour work week, 28,30 an average of 261 workdays per year and work duration of 10 years, an average lifetime daily exposure to acrylonitrile is estimated to be 146.4 μg/m 3 (lifetime daily exposure = 4.3 mg/m 3 x (8/24) hrs x (261/ 365) days x (10/70) years).…”

Section: Human Biological Plausibilitymentioning

confidence: 99%

“…The carcinogenicity of acrylonitrile in rodents has been extensively investigated and large-scale epidemiological studies have been conducted. While in humans most epidemiological studies produced no consistent findings of increased cancer risk associated with acrylonitrile exposure, 4–12 in rodent carcinogenicity bioassays, acrylonitrile produced tumors in multiple sites, including the brain, mammary gland, and Zymbal’s (auditory sebaceous tissue) gland of rats, forestomach of rats and mice, and Harderian (secretory orbital tissue) gland of mice. Increases in brain tumors observed in several acrylonitrile bioassays in male and female rats of two strains, 13,14 although not in mice, 15,16 led to a concern that acrylonitrile could be a central nervous system carcinogen in humans.…”

Section: Introductionmentioning

confidence: 99%

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Acrylonitrile induction of rodent neoplasia: Potential mechanism of action and relevance to humans

Kobets

Iatropoulos

Williams

2022

Toxicology Research and Application

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Acrylonitrile, an industrial chemical, is a multisite carcinogen in rats and mice, producing tumors in four tissues with barrier function, that is, brain, forestomach, Zymbal’s gland, and Harderian gland. To assess mechanism(s) of action (MoA) for induction of neoplasia and to evaluate whether the findings in rodents are indicative of human hazard, data on the potential key effects produced by acrylonitrile in the four rodent target tissues of carcinogenicity were evaluated. A notable finding was depletion of glutathione in various organs, including two target tissues, the brain, and forestomach, suggesting that this effect could be a critical initiating event. An additional combination of oxidative DNA damage and cytotoxic effects of acrylonitrile and its metabolites, cyanide, and 2-cyanoethylene oxide, could initiate pro-inflammatory signaling and sustained cell and tissue injury, leading to compensatory cell proliferation and neoplastic development. The in vivo DNA-binding and genotoxicity of acrylonitrile has been studied in several target tissues with no compelling positive results. Thus, while some mutagenic effects were reported in acrylonitrile-exposed rodents, data to determine whether this mutagenicity stems from direct DNA reactivity of acrylonitrile are insufficient. Accordingly, the induction of tumors in rodents is consistent primarily with a non-genotoxic MoA, although a contribution from weak mutagenicity cannot be ruled out. Mechanistic data to support conclusions regarding human hazard from acrylonitrile exposure is weak. Comparison of metabolism of acrylonitrile between rodents and humans provide little support for human hazard. Three of the tissues affected in bioassays (forestomach, Zymbal’s gland, and Harderian gland) are present only in rodents, while the brain is anatomically different between rodents and humans, diminishing relevance of tumor induction in these tissues to human hazard. Extensive epidemiological data has not revealed causation of human cancer by acrylonitrile.

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