The isolation and characterization of 2-carboxyethyl adducts following in vitro reaction of acrylic acid with calf thymus DNA and bioassay of acrylic acid in female Hsd: (ICR)Br mice

Segal, Alvin; Fedyk, John; Melchionne, Susan; Seidman, Irving

doi:10.1016/0009-2797(87)90039-1

Cited by 19 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Reactions of acrylic acid with 2 0 -deoxyadenosine , 2 0deoxycytidine, 2 0 -deoxyguanosine, and thymidine at pH 7.0 and 37 ± C for 40 days resulted in the formation of 2-carboxyethyl (CE) adducts via Michael addition (Segal et al 1987). 1-CEadenosine (1-CE-Ade), N 6 -CE-Ade, 7-CE-guanine, and 3-CEthymine were isolated after in vitro reaction of acrylic acid with calf thymus DNA at pH 7.0 and 37 ± C for 40 days.…”

Section: Genotoxicitymentioning

confidence: 99%

“…Acrylic Acid. Groups of 30 female Hsd:(ICR)Br mice were dosed with 20 ¹mol (1.4 mg) acrylic acid in 0.05 ml trioctanoin or vehicle only subcutaneously into the left ank once weekly for 52 weeks; the animals were then observed for an additional 93 days (450 total days on study) (Segal et al 1987). An untreated control group of 100 animals was observed for 450 days.…”

Section: Parenteralmentioning

confidence: 99%

See 1 more Smart Citation

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

M¹

2002

Int J Toxicol

View full text Add to dashboard Cite

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.

show abstract

Section: Genotoxicitymentioning

confidence: 99%

Section: Parenteralmentioning

confidence: 99%

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

M¹

2002

Int J Toxicol

View full text Add to dashboard Cite

show abstract

“…In an in vitro study of DNA binding, acrylic acid induced 2-carboxyethyl adducts with all four DNA bases after 40-day incubation with calf thymus DNA and the individual nucleosides at pH 7.0. The authors considered the reaction to be slow (Cote et al 1986b;Segal et al 1987). Since the very long incubation time makes it difficult to interpret the result, the DNA reactivity of acrylic acid is considered to be very slight in accordance with the authors' opinion.…”

Section: In Vitromentioning

confidence: 93%

“…No tumours were found in the untreated control animals and in those treated with trioctanoin. For comparison, the tumour incidence was 17/30 using the unequivocally carcinogenic β-propiolactone (4 µmol) at the same application frequency with the same strain of mice (Segal et al 1987). In laboratory rodents, sarcomas can be induced also after repeated subcutaneous application of large amounts of glucose, distilled water and sodium chloride (Grasso 1987).…”

Section: Subcutaneous Injectionmentioning

confidence: 99%

Acrylic acid [MAK Value Documentation, 2010]

2012

The MAK‐Collection for Occupational Health and Safety

View full text Add to dashboard Cite

Published in the series MAK Value Documentations , Vol. 26 (2010) The article contains sections titled: Toxic Effects and Mode of Action Mechanism of Action Toxicokinetics and Metabolism Absorption, distribution, elimination Metabolism Effects in Humans Animal Experiments and in vitro Studies Acute toxicity Subacute, subchronic and chronic toxicity Local effects on skin and mucous membranes Allergenic effects Reproductive toxicity Genotoxicity Carcinogenicity Manifesto (MAK value, classification)

show abstract

“…We N-i of A wher therefore studied the DNA adducts of acrylamide ( 18) boxylic acid as (AM) [CH2=CHCO(NH2)] and confirmed that AM can from ANO an( also react directly with DNA at endoyclic nitrogens to from the reac form formamidoethyl [CH2CH2CO(NH2)] adducts; when vinyl chloride this occurs adjacent to an exocyclic nitrogen, however, at N-3 of dCyc the amide is rapidly converted to a carboxylic acid. The dUrd, is show CE adducts that result at N-l of A and N-3 of C are thus of PO with dC common lesions that are produced by several rodent cargroup in the cinogens including P-propiolactone (11), AN (16), AM (18), hydrolytic de and acrylic acid (19).…”

Section: Propylene Oxidementioning

confidence: 99%

DNA Adducts of Propylene Oxide and Acrylonitrile Epoxide: Hydrolytic Deamination of 3-Alkyl-dCyd to 3-Alkyl-dUrd

Solomon¹,

Segal²

1989

Environmental Health Perspectives

Self Cite

View full text Add to dashboard Cite

Propylene oxide (PO) and acrylonitrile epoxide (ANO) are 3-carbon epoxides that are direct-acting mutagens. PO is a rodent carcinogen, and ANO has been postulated to be the ultimate carcinogenic form of acrylonitrile (AN). We have studied the reactions of these agents with 2 '-deoxynucleosides and in vitro with calf thymus DNA at pH 7.0 to 7.5 and 370C. PO was reacted with DNA for 10 hr and resulted in the formation of the following 2-hydroxypropyl (HP) adducts: N6-HP-dAdo (1 nmole/mg DNA), 3-HP-Ade (14 nmole/mg DNA), 7-HP-Gua (133 nmole/mg DNA) and 3-HP-dUrd (13 nmole/mg DNA). 3-HP-dUrd was formed after initial alkylation at N-3 of dCyd followed by conversion of the adjacent exocyclic imino group at C4 to an oxygen (hydrolytic deamination) with the formation of a dUrd adduct. ANO was reacted for 3 hr with calf thymus DNA and yielded N6-(2-hydroxy-2-carboxyethyl-dAdo (N6-HOCE-dAdo) (2 nmole/mg DNA); 1, N6-etheno-dAdo (11 nmole/mg DNA); 7-(2-oxoethyl)-Gua (7-OXE-Gua) (110 nmole/mg DNA); 3-OXE-dThd (1 nmole/mg DNA); and 3-HOCE-dUrd (80 nmole/mg DNA). As with 3-HP-dUrd, 3-HOCE-dUrd resulted from hydrolytic deamination of an initially formed dCyd adduct. A mechanism is proposed for the conversion of 3-alkyl-dCyd to 3-alkyl-dUrd involving intramolecular catalysis by the OH group on the 3-carbon side chain of the adduct. This cytosine to uracil conversion may be a common phenomenon with aliphatic epoxides and may play a role in the mutagenic and carcinogenic activity of this class of compounds.

show abstract

The isolation and characterization of 2-carboxyethyl adducts following in vitro reaction of acrylic acid with calf thymus DNA and bioassay of acrylic acid in female Hsd: (ICR)Br mice

Cited by 19 publications

References 10 publications

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

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

Acrylic acid [MAK Value Documentation, 2010]

DNA Adducts of Propylene Oxide and Acrylonitrile Epoxide: Hydrolytic Deamination of 3-Alkyl-dCyd to 3-Alkyl-dUrd

Contact Info

Product

Resources

About