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IARC Monographs on the Evaluation of... 1999
Review
Topics: Acrylonitrile; Animals; Carcinogenicity Tests; Carcinogens; Cohort Studies; Disease Models, Animal; Environmental Exposure; Global Health; Humans; Maximum Allowable Concentration; Mice; Neoplasms; Neoplasms, Experimental; Rats; Risk Factors
PubMed: 10476445
DOI: No ID Found -
Critical Reviews in Toxicology Feb 2023Acrylonitrile (ACN) is a known rodent and possible human carcinogen. There have also been concerns as to it causing adverse reproductive health effects. Numerous... (Review)
Review
Acrylonitrile (ACN) is a known rodent and possible human carcinogen. There have also been concerns as to it causing adverse reproductive health effects. Numerous genotoxicity studies at the somatic level in a variety of test systems have demonstrated ACN's mutagenicity; its potential to induce mutations in germ cells has also been evaluated. ACN is metabolized to reactive intermediates capable of forming adducts with macromolecules including DNA, a necessary first step in establishing a direct mutagenic mode of action (MOA) for its carcinogenicity. The mutagenicity of ACN has been well demonstrated, however, numerous studies have found no evidence for the capacity of ACN to induce direct DNA lesions that initiate the mutagenic process. Although ACN and its oxidative metabolite (2-cyanoethylene oxide or CNEO) have been shown to bind with isolated DNA and associated proteins, usually under non-physiological conditions, studies in mammalian cells or have provided little specification as to an ACN-DNA reaction. Only one early study in rats has shown an ACN/CNEO DNA adduct in liver, a non-target tissue for its carcinogenicity in the rat. By contrast, numerous studies have shown that ACN can act indirectly to induce at least one DNA adduct by forming reactive oxygen species (ROS) but it has not been definitively shown that the resulting DNA damage is causative for the induction of mutations. Genotoxicity studies for ACN in somatic and germinal cells are summarized and critically reviewed. Significant data gaps have been identified for bringing together the massive data base that provides the basis of ACN's current genotoxicity profile.
Topics: Rats; Humans; Animals; Mutagens; DNA Adducts; Acrylonitrile; Mutagenicity Tests; DNA Damage; DNA; Mammals
PubMed: 37278976
DOI: 10.1080/10408444.2023.2179912 -
Archiv Der Pharmazie Mar 2022Acrylonitrile is a fascinating scaffold widely found in many natural products, drugs, and drug candidates with various biological activities. Several drug molecules such... (Review)
Review
Acrylonitrile is a fascinating scaffold widely found in many natural products, drugs, and drug candidates with various biological activities. Several drug molecules such as entacapone, rilpivirine, teriflunomide, and so forth, bearing an acrylonitrile moiety have been marketed. In this review, diverse synthetic strategies for constructing desired acrylonitriles are discussed, and the different biological activities and medicinal significance of various acrylonitrile derivatives are critically evaluated. The information gathered is expected to provide rational guidance for the development of clinically useful agents from acrylonitriles.
Topics: Acrylonitrile; Structure-Activity Relationship
PubMed: 34763365
DOI: 10.1002/ardp.202100383 -
Lancet (London, England) Jun 1984
Topics: Acrylonitrile; Animals; Humans; International Cooperation; Mutagenicity Tests; Nitriles; Rats; World Health Organization
PubMed: 6144932
DOI: No ID Found -
Scandinavian Journal of Work,... 1998Acrylonitrile is a monomer used extensively as a raw material in the manufacturing of acrylic fibers, plastics, synthetic rubbers, and acrylamide. It has been classified... (Review)
Review
Acrylonitrile is a monomer used extensively as a raw material in the manufacturing of acrylic fibers, plastics, synthetic rubbers, and acrylamide. It has been classified as a probable human carcinogen according to the results of numerous chronic rat bioassays. The present report summarizes the toxicity data on acrylonitrile and reviews available data concerning the mechanism (genetic versus epigenetic) by which acrylonitrile is carcinogenic in rats. From the evaluation of the relevant toxicity data, it can be concluded that acrylonitrile is indeed carcinogenic to rats after either oral or inhalational exposure. However, information on other mammalian species is lacking, and, moreover, the exact mechanism of the carcinogenic process is unclear. Therefore, it is recommended to conduct an additional long-term inhalation carcinogenicity study with acrylonitrile in mice, as well as studies into the mechanism by which acrylonitrile induces (brain) tumors in rats (genetic versus epigenetic).
Topics: Acrylonitrile; Administration, Oral; Animals; Carcinogens; Disease Models, Animal; Dogs; Guinea Pigs; Humans; Inhalation Exposure; Lethal Dose 50; Mice; Mutagens; Rabbits; Rats; Risk Assessment
PubMed: 9714508
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2002
Topics: Acrylonitrile; Animals; Carcinogens; Environmental Exposure; Government Regulation; Humans; United States
PubMed: 15317112
DOI: No ID Found -
Food Additives & Contaminants. Part A,... Feb 2022Styrene-acrylonitrile-copolymer (SAN) and acrylonitrile-butadiene-styrene-copolymer (ABS) are gaining in importance as food contact materials. Oligomers and other...
Styrene-acrylonitrile-copolymer (SAN) and acrylonitrile-butadiene-styrene-copolymer (ABS) are gaining in importance as food contact materials. Oligomers and other non-intentionally added substances can migrate into foodstuffs. Five SAN and four ABS samples from the German market and manufacturers were extracted and the extractable oligomers were characterised by high performance liquid chromatography-mass spectrometry/ultraviolet detection/chemiluminescence nitrogen detection/fluorescence detection and gas chromatography-mass spectrometry. Trimers, formed from acrylonitrile and styrene units, were determined to be the dominating group of extractable oligomers in SAN and ABS in concentrations of about 4900-15800 mg/kg material. Furthermore, styrene-acrylonitrile dimers, styrene oligomers, styrene monomer and ethylbenzene were identified in the sample extracts. Migration testing with three consecutive migrations for multiple use articles was performed for two SAN articles. Migration of trimers into water, 3% acetic acid, 10% and 20% ethanol under conditions (70°C, 2 h) was not detectable above 9 µg/dm, while 50% ethanol acting as a food simulant for milk (124 µg/dm trimers during the third migration) was shown to overestimate the actual migration into milk (< 11 µg/dm trimers at 70°C, 2 h). 2-Amino-3-methyl-1-naphthalenecarbonitrile (AMNC), an oligomer degradation product and a primary aromatic amine, was detected in all material sample extracts (0.3-17.1 mg/kg material) and was released into food simulants in low amounts (< 0.014 µg/dm during the third migration into 50% ethanol at 70°C, 2 h).
Topics: Acrylonitrile; Butadienes; Food Analysis; Food Contamination; Polymers; Styrene
PubMed: 34780321
DOI: 10.1080/19440049.2021.1995631 -
Chemico-biological Interactions Jun 2022Acrylonitrile is an organic chemical synthetic monomer that is widely used in food packaging and manufacturing. Animal studies have reported that acrylonitrile is...
Acrylonitrile is an organic chemical synthetic monomer that is widely used in food packaging and manufacturing. Animal studies have reported that acrylonitrile is carcinogenic and toxic, but the effects on the female reproductive function in mammals are unknown. In the present study, we report that acrylonitrile treatment affects ovarian homeostasis in mice, resulting in impaired follicular development. Follicles in acrylonitrile-exposed mice exhibited high levels of inflammation and apoptosis, and acrylonitrile treatment interfered with oocyte development. Transcriptomics analysis showed that acrylonitrile altered the expression of oocyte genes related to apoptosis, oxidative stress, endoplasmic reticulum stress, and autophagy. Further molecular tests revealed that acrylonitrile induced early apoptosis, DNA damage, elevated levels of reactive oxygen species, endoplasmic reticulum abnormalities, and lysosomal aggregation. We also observed disruption of mitochondrial structure and distribution and depolarization of membrane potential. Finally, acrylonitrile treatment in female mice decreased the number and weight of offspring. Altogether, these findings suggest that acrylonitrile impairs the stability of the ovarian internal environment, which in turn affects oocyte development and reduces the number of offspring.
Topics: Acrylonitrile; Animals; Apoptosis; Female; Inflammation; Mammals; Mice; Mitochondria; Oocytes
PubMed: 35429547
DOI: 10.1016/j.cbi.2022.109934 -
Report on Carcinogens : Carcinogen... 2011
Topics: Acrylonitrile; Animals; Carcinogens; Humans; Neoplasms
PubMed: 21829241
DOI: No ID Found -
Inhalation Toxicology Dec 2009Application of Provisional Advisory Level (PAL) protocols was performed for acrylonitrile, as experimental data permitted. Three levels (PAL 1, PAL 2, and PAL 3),... (Review)
Review
Application of Provisional Advisory Level (PAL) protocols was performed for acrylonitrile, as experimental data permitted. Three levels (PAL 1, PAL 2, and PAL 3), distinguished by severity of toxic effects, are developed for 24-hour, 30-day, 90-day, and 2-year durations of potential drinking water and inhalation exposures for the general public. For background on the PAL Program and a description of the methodology used in deriving PALs, the reader is referred to accompanying papers in this Supplement. Human data were limited to inhalation exposures. The animal experimental data set for this chemical was robust for inhalation and oral studies, with the exception of appropriate data for inhalation 30-day, 90-day, and 2-year PAL 3 values. PAL estimates were approved by the Expert Consultation Panel for Provisional Advisory Levels in October 2007. Oral 24-hour PALs for acrylonitrile are PAL 1 = 7 mg/L; PAL 2 = 23 mg/L; and PAL 3 = 88 mg/L. Oral 30-day and 90-day PALs are PAL 1 = 0.35 mg/L; PAL 2 = 7 mg/L; and PAL 3 = 17 mg/L. Oral 2-year PALs are PAL 1 = 0.35 mg/L; PAL 2 = 3.5 mg/L; and PAL 3 = 12 mg/L. Acrylonitrile inhalation PAL values for 24-hour exposure are PAL 1 = 0.17 ppm; PAL 2 = 3.5 ppm; and PAL 3 = 5.1 ppm; the 30-day and 90-day inhalation exposure values are PAL 1 = 0.15 ppm and PAL 2 = 0.60 ppm. The 2-year inhalation values are PAL 1 = 0.014 ppm and PAL 2 = 0.12 ppm. PAL 3 values for 30 days, 90 days, and 2 years are not recommended due to insufficient data.
Topics: Acrylonitrile; Animals; Consultants; Environmental Exposure; Humans; Inhalation Exposure; Occupational Exposure
PubMed: 19827913
DOI: 10.3109/08958370903202804