Reproductive & Developmental Effects

Technical Summary:

Short chain alkyl-methacrylate esters (MMA, EMA, nBMA, iBMA and 2-EHMA) are high production volume chemicals and have been reviewed extensively by government regulatory agencies. None of these reviews have identified these materials as reproductive or developmental toxicants. Reviews were completed by European Union and OECD Existing Chemicals Risk Assessment programs. MMA has been the subject of an EU Risk Assessment (2002) and OECD review (2007). EMA, nBMA, iBMA and 2-EHMA underwent review as a category in the OECD CICAD program (2009). Data on MAA, a metabolite common to all of the methacrylate esters, has also been reviewed in the EU Risk Assessment (2002).

Definitive reproductive and developmental toxicity tests are available for MMA while screening studies are available for other methacrylate esters. MMA was least harmful to maternal animals and also was not harmful to the fetus. As chain length increases, maternal toxicity accompanied by fetal toxicity increases. However, no selective effect on reproduction or fetal development was observed for any ester or for methacrylic acid.

In a recently conducted 2-generation reproduction toxicity study, MMA was administered to groups of Wistar rats at doses of 0, 50, 150 and 400 mg/kg body weight/day. The NOAEL for maternal, systemic toxicity was 50 mg/kg bw/day while the NOAEL for fertility and reproductive performance and effects on development was 400 mg/kg MMA (Schneider et al 2010a). Reproductive effects observed in earlier one-generation screening studies for n-BMA and EHMA were not confirmed in this study.

MMA did not cause developmental effects in rats even at inhalation exposure levels that caused maternal toxicity. High inhalation exposures to n-BMA and EMA in rats reduced fetal body weight, but were not teratogenic even at concentrations producing overt maternal toxicity. (Saillenfait et al., 1999) Follow-up oral exposure developmental toxicity studies on MMA and nBMA were conducted in rabbits. MMA was administered to pregnant rabbits orally at doses of 50; 150 and 450 mg/kg body weight/day and nBMA at doses of 100, 300 and 1000 mg/kg body weight/day. No selective effect of either compound on development was found; no fetal effects occurred in the absence of maternal toxicity. (MRTF Studies). Based on these studies, MMA, EMA and nBMA are not selective developmental toxins in rabbits or rats.

Methacrylic acid (MAA), the common metabolite for all the esters, has been tested in groups of pregnant female rats (whole-body inhalation exposure for 6 hr/day, during days 6 to 20 of gestation), at 0, 50, 100, 200, and 300 ppm. No adverse effects on development were found even at exposure levels causing overt maternal toxicity. (Schneider et al 2010b and Schneider et al 2010c)

Extensive reproductive and developmental toxicity studies of MMA and other methacrylate esters including methacrylic acid itself, as described above, indicate that these substances are not selective reproductive or developmental toxicants.

References:

Saillenfait AM, Bonnet P, Gallissot F, Peltier A and Fabries JF. Developmental Toxicities of Methacrylic Acid, Ethyl Methacrylate, n-Butyl Methacrylate, and Allyl Methacrylate in Rats following Inhalation Exposure. Toxicological Sciences 50, 136-145 (1999).

Schneider, S., Fabian, E., and Ravenzwaay, B. (a) n-Butyl Methacrylate Prenatal Developmental Toxicity Study in Himalayan Rabbits Oral Administration (Gavage). November 19, 2010. Lab: BASF Corporation, Project 40R0538/07099. Study Sponsor: Methacrylate REACH Task Force.

Schneider, S., Fabian, E., and Ravenzwaay, B. (b) Methyl Methacrylate Prenatal Developmental Toxicity Study in Himalayan Rabbits Oral Administration (Gavage). November 19, 2010. Lab: BASF Corporation, Project 40R0751/07093. Study Sponsor: Methacrylate REACH Task Force.

Schneider, S., Strauss, V, Treumann, S., and Ravenzwaay, B. (c) Methyl Methacrylate Two-Generation Reproduction Toxicity Study in Wistar Rats Oral Administration (Gavage). October 15, 2010. Lab: BASF Corporation, Project 73R0751/07101. Study Sponsor: Methacrylate REACH Task Force.