Subchronic and chronic studies of the effects of oral administration of acrylic acid to rats

Hellwig, J.; Deckardt, K.; Freisberg, K.O.

doi:10.1016/0278-6915(93)90172-u

Cited by 23 publications

(15 citation statements)

References 16 publications

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“…The first reaction of the propionate shunt produces acrylyl-CoA, a highly toxic and reactive metabolite ( Hellwig et al, 1993 ; Saillenfait et al, 1999 ). Since we predict that acrylyl-CoA is the substrate of ECH-6, we hypothesized that ech-6 perturbation would result in a severe phenotype due to toxic buildup of acrylyl-CoA or its hydrolyzed derivative acrylate.…”

Section: Resultsmentioning

confidence: 99%

Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans

Watson

Olín-Sandoval

Hoy

et al. 2016

eLife

112

212

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Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild.DOI: http://dx.doi.org/10.7554/eLife.17670.001

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Section: Resultsmentioning

confidence: 99%

Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans

Watson

Olín-Sandoval

Hoy

et al. 2016

eLife

112

212

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“…Groups of 10 male and 10 female Wistar rats were given 150 or 375 mg/kg aqueous acrylic acid by gavage 5 days per week for 3 months; a control group was given water by gavage (Hellwig, Deckardt, and Freisberg 1993). Feed and water consumption and body weights were determined weekly.…”

Section: Oralmentioning

confidence: 99%

Final Report on the Safety Assessment of Acrylates Copolymer and 33 Related Cosmetic Ingredients

M¹

2002

Int J Toxicol

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Ingredients in the Acrylates Copolymer group all contain the monomers acrylic acid or methacrylic acid or one of their salts or esters. These ingredients are considered similar in that they are uniformly produced in chemical reactions that leave very little residual monomer. Although residual acrylic acid may be as high as 1500 ppm, typical levels are 10 to 1000 ppm. There is sufficient odor if residual monomers are present to cause producers to keep levels as low as possible. These ingredients function in cosmetics as binders, film formers, hair fixatives, suspending agents, viscosity-increasing agents, and emulsion stabilizers. Concentrations may be as high as 25% if used as a binder, film former, or fixative; or as low as 0.5% if used as a viscosity-increasing agent, suspending agent, or emulsion stabilizer. These very large polymers exhibit little toxicity. In rabbits and guinea pigs, Acrylates Copolymer did produce irritation, but no evidence of sensitization was found. The principle concern regarding the use of these polymer ingredients is the presence of toxic residual monomers. In particular, although 2-ethylhexyl acrylate was not genotoxic, it was carcinogenic when applied at a concentration of 21% to the skin of C3H mice. Lower concentrations (2.5%) and stop-dose studies at high concentrations (43%) were not carcinogenic. 2-Ethylhexyl acrylate was not carcinogenic in studies using NMRI mice. Whether an increase in carcinogenesis was seen or not, there was evidence of severe dermal irritation in these 2-ethylhexyl acrylate studies. Another concern regarding residual monomers was inhalation toxicity. Although the acrylic acid monomer is a nasal irritant, exposure to the monomer from use of these polymers in cosmetic formulations would always be less than the established occupational exposure limits for nasal irritation. Although there appears to be a huge variation in the mix of monomers used in the synthesis of these polymers, they are similar in that the polymers, except for dermal irritation, are not significantly toxic, and residual monomer levels are kept as low as possible. Although the monomers may be toxic, the levels that would be found in cosmetic formulations are not considered to present a safety risk. Accordingly, these Acrylate Copolymers are considered safe for use in cosmetic formulations when formulated to avoid irritation.

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“…Acrylic acid, a metabolite of ethyl acrylate, was given to Wistar rats during 12 months in drinking water, containing 120, 800, 2,000 or 5,000 mg/L, providing doses of about 9, 61, 140 and 331 mg/kg bw per day, according to the authors (Hellwig et al., ). The two highest doses led to reduced consumption of drinking water, indicating palatability problems.…”

Section: Procedures Of the Safety Assessmentmentioning

confidence: 99%

Safety of ethyl acrylate to be used as flavouring

Silano¹,

Bolognesi²,

Castle³

et al. 2017

EFS2

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JECFA (2006) and EFSA (2010). Moreover, new data on the use levels of ethyl acrylate as flavouring substance have been provided. For use as flavouring substance, the chronic dietary exposure estimated using the added portions exposure technique (APET), is calculated to be 3,545 lg/person per day for a 60-kg adult and 2,233 lg/person per day for a 15-kg 3-year-old child. Exposure from food contact materials may be up to 6,000 lg/person per day. The Panel considered that based on the available data, which covers all relevant genetic endpoints (i.e. gene mutations, structural and numerical chromosomal aberrations) there is no concern with respect to genotoxicity of ethyl acrylate. The Panel evaluated the available carcinogenicity studies conducted in rats and mice and agreed with the NTP evaluation (1998) concluding that the forestomach squamous cell papilloma and carcinoma observed in rodents were not relevant to humans. Additionally, there was no evidence of systemic toxicity in short-term and subchronic toxicity studies. Therefore, the Panel concluded that there is no safety concern for the use of ethyl acrylate as a flavouring substance, under the intended conditions of use.

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Subchronic and chronic studies of the effects of oral administration of acrylic acid to rats

Cited by 23 publications

References 16 publications

Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans

Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans

Final Report on the Safety Assessment of Acrylates Copolymer and 33 Related Cosmetic Ingredients

Safety of ethyl acrylate to be used as flavouring

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