Reaction products of methacrylic acid and 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Endpoint summary

Additional information

Small Vinyl Ester is a multi-constituent substance. Its generic composition is seen in Section 1.2. Exposure to Small Vinyl Ester will result in exposure to all the constituents. No toxicokinetic data are available on Small Vinyl Ester. Thus QSAR estimations were performed on several of the constituents.

Oral absorption

Oral absorptions were estimated using MultiCase (MC4PC v2.1.0.18), cf. Section 13 (QSAR evaluations). Relative oral absorption rates were estimated for bisGMA, epoxy-monoGMA and dihydroxy-monoGMA. The following relative oral absorption rates were found:

bisGMA                         82%

epoxy-monoGMA          91%

dihydroxy-monoGMA    64%

It is judged that methacrylic acid is orally absorbed to 100%.

These constituents contribute to the total relative oral absorption proportionally to their relative amount in Small Vinyl Ester. Thus it is calculated that Small Vinyl Ester is absorbed orally by 80%. This is confirmed in guinea pigs for bisGMA using radiotracer technique (Reichl et al, 2008 & 2008a).

Dermal absorption

Dermal absorptions were calculated using US-EPA EPIsuite v4.1, cf. Section 7.1.2 (dermal absorption.001). Relative dermal absorption rates for bisGMA, epoxy-monoGMA, dihydroxy-monoGMA and methacrylic acid were calculated for three exposure times (1 h, 8 h and 24 h) based on the QSAR estimations of the dermal absorptions. The relative dermal absorption rates were calculated to approximately 0.035% at 8 h contact time for dihydroxy-monoGMA and even lower for bisGMA, epoxy-monoGMA and polymeric reaction products (judgement), and for shorter contact times. These low dermal absorption rates are negligible in the risk assessment context.

Only for the residual monomer, methacrylic acid the relative absorption rate is not negligible; it was calculated to 9.1, 47.9 and 100%, respectively for 1-hour, 8-hours and 24-hours skin contact. However, it should kept in mind during risk assessment that the calculated systemic dose at 24-hours skin contact (1980 cm2) is 45 mg/kg bw, which is approximately 24 times lower than the lowest LD50 found in rats.

Inhalation absorption

Vapour pressures were calculated using US-EPA EPIsuite v4.0, cf. Section 13 (QSAR evaluations). Vapour pressures were estimated for bisGMA, epoxy-monoGMA, dihydroxy-monoGMA and methacrylic acid. The following vapour pressures were found:

bisGMA                         2.0e-13 Pa

epoxy-monoGMA          1.7e-10 Pa

dihydroxy-monoGMA    7.7e-14 Pa

methacrylic acid              132 Pa

The vapour pressures of bisGMA, epoxy-monoGMA, dihydroxy-monoGMA, and also polymeric reaction products (judged) are negligible and will not give to inhalation exposure of vapours.

The vapour pressure of the residual monomer methacrylic acid has a significant vapour pressure that may give rise to inhalation exposure. However, it should be kept in mind during risk assessment that methacrylic acid amounts less than 1% of Small Vinyl Ester and most likely methacrylic acid has affinity to stay in the product.

Distribution and metabolism

The study of Reichl et al (2008, 2008a) showed that bisGMA is rapidly excreted from the body (guinea pigs), only 6% remaining 24 hours after oral exposure. One hour after i.v. injection bisGMA was found in the lungs (22%), the brain (2%) and kidneys (2%); less than 0.1% in tissues of each of heart, testes, spleen, skin, blood. muscle and fat. The high concentration in the lungs led Reichl et al to propose that metabolism of bisGMA primarily takes place in the lungs.

Excretion

More than 65% of an oral dose of bisGMA to guinea pigs was exhaled as CO2 during the first 24 hours. 7% was excreted via the bile.