Studies on the chronic oral toxicity of monomeric ethyl acrylate and methyl methacrylate

Borzelleca, Joseph F.; Larson, Paul; Hennigar, Gordon R.; Huf, Ernst G.; Crawford, E.M.; Smith, Robert B.

doi:10.1016/0041-008x(64)90019-5

Cited by 74 publications

(32 citation statements)

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“…Two-year inhalation studies in rats and mice gave no evidence of carcinogenicity (384). A 2-year drinking water study in rats was also negative for carcinogenicity (388); however, local tumors may be formed at the site of methyl methacrylate implants; the International Agency for Research on Cancer considers methyl methacrylate not classifiable with regard to human carcinogenicity (157). Methyl methacrylate appears not to be teratogenic but has shown embryoand fetotoxicity on maternal inhalation exposure (157,386).…”

Section: Gamentioning

confidence: 99%

See 1 more Smart Citation

The sources, fate, and toxicity of chemical warfare agent degradation products.

Munro

Talmage

Griffin

et al. 1999

Environ Health Perspect

530

501

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We indude in this review an assessment of the formation, environmental fate, and mammalian and ecotoxicity of CW agent degradation products relevant to environmental and occupational health.These parent CW agents indude several vesicants: sulfur mustards [undistilled sulfur mustard (H), sulfur mustard (HD), and an HD/agent T mixture (HT)]; nitrogen mustards [ethylbis(2-chloroethyl)amine (HN1), methylbis(2-chloroethyl)amine (HN2), tris(2-chloroethyl)amine (HN3)], and Lewisite; four nerve agents {O0ethyl S.[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), tabun (GA), sarin (GB), and soman (GD)}; and the blood agent cyanogen chloride. The degradation processes considered here include hydrolysis, microbial degradation, oxidation, and photolysis. We also briefly address decontamination but not combustion processes. Because CW agents are generally not considered very persistent, certain degradation products of significant persistence, even those that are not particularly toxic, may indicate previous CW agent presence or that degradation has occurred. Of those products for which there are data on both environmental fate and toxicity, only a few are both environmentally persistent and highly toxic. Major degradation products estimated to be of significant persistence (weeks to years) indude thiodiglycol for HD; Lewisite oxide for Lewisite; and ethyl methyl phosphonic acid, methyl phosphonic acid, and possibly S.(2-diisopropylaminoethyl) methylphosphonothioic acid (EA 2192) for VX. Methyl phosphonic acid is also the ultimate hydrolysis product of both GB and GD. The GB product, isopropyl methylphosphonic acid, and a dosely related contaminant of GB, diisopropyl methylphosphonate, are also persistent. Of all of these compounds, only Lewisite oxide and EA 2192 possess high mammalian toxicity. Unlike other CW agents, suifur mustard agents (e.g., HD) are somewhat persistent; therefore, sites or conditions involving potential HD contamination should include an evaluation of both the agent and thiodiglycol.

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Section: Gamentioning

confidence: 99%

“…A chronic RfD of 0.08 mglkg/day has been calculated, based on a NOEL of 7.5 mg/kg/day during a 24-month oral exposure of rats and the end point of increased relative kidney weight (388) together with an uncertainty factor of 100 (397).…”

Section: Gamentioning

confidence: 99%

The sources, fate, and toxicity of chemical warfare agent degradation products.

Munro

Talmage

Griffin

et al. 1999

Environ Health Perspect

530

501

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“…In an insufficiently documented 21-day oral rat study, effects on behaviour (listlessness, locomotoric activity, learning ability, gait and rear leg function), and changes in brain chemistry and peripheral nervous system were observed at 500 mg/kg body weight (Husain et al, 1985). In an early 2-year study on Beagle dogs and Wistar rats treated orally with methyl methacrylate, histopathological findings on brains revealed no abnormalities or lesions attributable to the test material (Borzelleca et al, 1964). However, other parameters for neurotoxicity such as brain chemistry were not investigated and clinical observations on behaviour were not reported.…”

Section: Considerations Of Combined Intakes From Use As Flavouring Sumentioning

confidence: 99%

“…"From the two-year drinking water study in rats (Borzelleca et al, 1964) a NOAEL of 200 mg/kg body weight/day (2000 ppm) was derived. "…”

Section: Evaluations From Other Expert Groupsmentioning

confidence: 99%

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to Flavouring Group Evaluation 5 (FGE.05); Esters of 23 branched- and straight-chain aliphatic saturated primary alcohols and

2005

EFSA Journal

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SUMMARYThe present Flavouring Group Evaluation deals with 24 esters with branched-and straight-chain aliphatic saturated primary alcohols (including one secondary alcohol) and branched-and straightchain unsaturated carboxylic acids.Nineteen of the 24 flavouring substances can exist as geometrical isomers. In 11 of these cases, no indication has been given that one of the possible isomers has preponderance in the commercial flavouring material. In addition, one candidate substance possesses a chiral centre.Twenty-one of them belong to structural class I while three substances were assigned to structural class II.Twenty-two of the substances in the present group of 24 substances have been reported to occur naturally in a wide range of food items.In its evaluation, the Panel as a default used the Maximised Survey-derived Daily Intakes (MSDIs) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European flavouring industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach. Flavouring Evaluation Group 05The EFSA Journal (2005) 204 Esters of 23 branched-and straight-chain aliphatic saturated primary alcohols and of one secondary alcohol, and 24 branched-and straightchain unsaturated carboxylic acids from chemical groups 1, 2, and 5 2In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a modified Theoretical Added Maximum Daily Intake (mTAMDI) approach based on the normal use levels reported by industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels.According to the default MSDI approach, the 24 flavouring substances in this group have intakes in Europe from 0.0012 to 1.7 microgram/capita/day which are below the threshold of concern value for both structural class I (1800 microgram/person/day) and structural class II (540 microgram/person/day) substances.All 24 flavouring substances are expected to participate in common routes of absorption, distribution and metabolism, and exhibit similar toxicological properties. Data for short and medium length linear and branched-chain alcohols and the carboxylic acids included in the present Flavouring Group Evaluation and general information for this c...

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“…Thus, Deichmann (1941) and Spealman et al (1945) found that, in small laboratory animals, these substances were less acutely toxic than ethyl acetate with an s.c. LD50 of 5000 mg/kg in rats, and that the most characteristic effects, caused by prolonged exposure to methyl methacrylate vapour, were degenerative changes of the liver. Chronic long-term toxicity testing of methyl methacrylate in dogs and rats by oral route (Borzelleca et al, 1964) failed to reveal an increased mortality amongst the animals, or any histological changes. The dogs were given gelatin capsules containing methyl methacrylate, in solution in corn oil, for a period of 2 years, in amounts equivalent to 10, 100 and 1000-1500 parts/106 in the diet, and the rats received concentrations of 6-7, 60-70 and 2000 parts/ 106 in their drinking water.…”

mentioning

confidence: 96%