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2628. Monomeric methacrylates and rat reproduction
THE
CHEMICAL
administration, this study raises doubts aetiological factor in haloalkane toxicity.
2628. Monomeric
methacrylates
ENVIRONMENT
about the theory
1151
that such conjugation
is an
and rat reproduction
Singh, A. R., Lawrence, W. H. & Autian, J. (1972). Embryonic-foetal toxicity and teratogenie effects of a group of methacrylate esters in rats. J. dent. Res. 51, 1632. Methacrylate resins are widely used for dental prostheses and contact lenses, as well as in a variety of industrial applications. It is said that by 1946, 98 ‘A of all dentures contained methyl methacrylate polymers or copolymers. As with most polymers, there is a possibility that small amounts of residual monomer may be present in the polymeric product and may be leached out during use. Allergic reactions to acrylic dentures, for example, have been attributed to the presence of the monomer (Cited in F.C.T. 1971, 9, 145). The toxicity of methacrylic ester monomers, particularly of the methyl ester, has received considerable attention and it is known that acutely toxic doses given by various routes cause death by respiratory depression. Prolonged inhalation of the methyl ester leads to degenerative changes in the liver, but no pathological lesions were found in dogs fed up to 1000 ppm methyl or ethyl methacrylate in the diet for 2 yr (ibid 1964, 2, 503). However, there has been little information about the embryotoxic or teratogenic effects of these esters, and in this connexion a study now reported compares the effects of several methacrylate monomers and acrylic acid administered ip to pregnant rats. The three dose levels used were 10, 20 and 33 % of the acute ip LDSo values, determined as 1.33, 1.22, 2.30, 1.40, 2.47 and O-02 ml/kg for the methyl, ethyl, n-butyl, isobutyl and isodecyl methacrylates and acrylic acid, respectively. Each dose level was given undiluted to groups of five pregnant Sprague-Dawley rats on days 5, 10 and 15 of gestation, and four control groups were given cottonseed oil, distilled water, normal saline or no treatment. The animals were killed on day 20 and a careful study of resorptions, stillbirths, gross malformations, skeletal malformations and foetal size was carried out. Both acrylic acid and the methacrylate esters evoked a dose-related response in terms of resorptions and gross and skeletal malformations. In comparison with the untreated controls, all the treated groups showed adverse effects in some or all of the parameters studied. However, in an attempt to eliminate effects resulting from the trauma of injection and handling, comparisons were also made with a “volume control” derived from the pooled results of the three treated control groups, which received injections equivalent in volume to the largest doses of the test compounds. On this basis, a significantly increased incidence of resorptions was associated with all three dose levels of ethyl methacrylate, the high doses of the n-butyl and isobutyl esters and the two highest dose levels of the isodecyl ester. Gross abnormalities, of which haemangioma was the most common, were increased in all the test groups except those given the low dose of methyl methacrylate or acrylic acid and the two lowest doses of the n-butyl ester, but only the group given the top-level dose of acrylic acid showed an incidence of skeletal malformations outside the 95% confidence interval (l-O14.8 %) for the pooled volume control. Among the methacrylate esters, the isodecyl proved the most toxic to the early embryo, with a high incidence of resorptions, and the methyl and ethyl esters produced the most gross abnormalities. Of the latter two groups, only the ethyl showed skeletal abnormalities, however.
CHEMICAL
administration, this study raises doubts aetiological factor in haloalkane toxicity.
2628. Monomeric
methacrylates
ENVIRONMENT
about the theory
1151
that such conjugation
is an
and rat reproduction
Singh, A. R., Lawrence, W. H. & Autian, J. (1972). Embryonic-foetal toxicity and teratogenie effects of a group of methacrylate esters in rats. J. dent. Res. 51, 1632. Methacrylate resins are widely used for dental prostheses and contact lenses, as well as in a variety of industrial applications. It is said that by 1946, 98 ‘A of all dentures contained methyl methacrylate polymers or copolymers. As with most polymers, there is a possibility that small amounts of residual monomer may be present in the polymeric product and may be leached out during use. Allergic reactions to acrylic dentures, for example, have been attributed to the presence of the monomer (Cited in F.C.T. 1971, 9, 145). The toxicity of methacrylic ester monomers, particularly of the methyl ester, has received considerable attention and it is known that acutely toxic doses given by various routes cause death by respiratory depression. Prolonged inhalation of the methyl ester leads to degenerative changes in the liver, but no pathological lesions were found in dogs fed up to 1000 ppm methyl or ethyl methacrylate in the diet for 2 yr (ibid 1964, 2, 503). However, there has been little information about the embryotoxic or teratogenic effects of these esters, and in this connexion a study now reported compares the effects of several methacrylate monomers and acrylic acid administered ip to pregnant rats. The three dose levels used were 10, 20 and 33 % of the acute ip LDSo values, determined as 1.33, 1.22, 2.30, 1.40, 2.47 and O-02 ml/kg for the methyl, ethyl, n-butyl, isobutyl and isodecyl methacrylates and acrylic acid, respectively. Each dose level was given undiluted to groups of five pregnant Sprague-Dawley rats on days 5, 10 and 15 of gestation, and four control groups were given cottonseed oil, distilled water, normal saline or no treatment. The animals were killed on day 20 and a careful study of resorptions, stillbirths, gross malformations, skeletal malformations and foetal size was carried out. Both acrylic acid and the methacrylate esters evoked a dose-related response in terms of resorptions and gross and skeletal malformations. In comparison with the untreated controls, all the treated groups showed adverse effects in some or all of the parameters studied. However, in an attempt to eliminate effects resulting from the trauma of injection and handling, comparisons were also made with a “volume control” derived from the pooled results of the three treated control groups, which received injections equivalent in volume to the largest doses of the test compounds. On this basis, a significantly increased incidence of resorptions was associated with all three dose levels of ethyl methacrylate, the high doses of the n-butyl and isobutyl esters and the two highest dose levels of the isodecyl ester. Gross abnormalities, of which haemangioma was the most common, were increased in all the test groups except those given the low dose of methyl methacrylate or acrylic acid and the two lowest doses of the n-butyl ester, but only the group given the top-level dose of acrylic acid showed an incidence of skeletal malformations outside the 95% confidence interval (l-O14.8 %) for the pooled volume control. Among the methacrylate esters, the isodecyl proved the most toxic to the early embryo, with a high incidence of resorptions, and the methyl and ethyl esters produced the most gross abnormalities. Of the latter two groups, only the ethyl showed skeletal abnormalities, however.