Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Data availability:

Regarding fertility, there is screening-level information on MAA (90 d inhalation study). Sufficient data to address all reproductive endpoint can be obtained by read-across from a 2-generation reproductive toxicity study on MMA by the oral route. No further testing is proposed.

Non-human data

In a OECD 413 90-day inhalation study 10 male and 10 female Sprague Dawley rats were whole body exposed to target concentrations of 20, 40, 100 and 350 ppm (corresponding to 72, 143, 358 and 1253 mg/m3) MAA for 6 hrs/d, 5 days/wk for 90 days (65 exposures; BASF 2008). In addition to examination of the standard organs and tissues, the sexual organs and parameters of fertility were examined. These examinations included weighing of sexual organs in both males and females and sperm mobility, morphology and sperm head count in one testis and one epididymis of each male animal of the high concentration and control group. Substance-related changes of the sexual organs were not noted in any of the exposed animals (males or females), nor were there any changes of sperm mobility and sperm head counts. Under the current test conditions, the NOAEC for fertility related parameters was 350 ppm (1253 mg/m3) for male and female rats.

While there is no full reproduction study with MAA, Methyl methacrylate has recently been tested in an OECD TG 416 oral two-generation reproduction toxicity study in rats, in which both, parental and F1 animals were dosed with 0; 50; 150 and 400 mg/kg body weight/day (BASF, 2009a)

In mid- and high-dose parental animals (150 and 400 mg/kg bw/d) temporary salivation, presumably due to a bad taste of the test substance and associated dose-related intermittent reductions of food consumption were noted. Less significant changes were noted for the F1 generation animals where the effects were limited to the high-dose group and not associated with effects on histopathology or reproductive performance.

The NOAEL for fertility and reproductive performance for the P and F1 parental rats was determined to be 400 mg/kg bw/day, the highest dose tested. The NOAEL for developmental toxicity, in the F1 and F2 progeny, of the test substance was determined to be 400 mg/kg bw/day, the highest dose tested. There were no signs of systemic toxicity other than reduced body weight gain associated with reduced food consumption, presumably due to bad palatability (NOEL 50 mg/kg bw/day for the P and F1 parental rats and LOEL of 150 mg/kg bw/day in the P parental females).

Human data

No reliable data available for any members of the category.


Short description of key information:
BASF(2008) No effects in sexual organs (histopathology, sperm count and morphology) in 90 d inhalation study up to 350 ppm (1232 mg/kg/d)
BASF (2009a) 2-gen study (OECD 414); read-across from MMA; no effect on fertility up to 400 mg MMA/kg/d, equivalent to 344 mg/kg/d MAA

Effects on developmental toxicity

Description of key information
Saillenfait et al. (1999): Developmental study in rats; No effects on development up to 300 ppm (1232 mg/m³), equivalent to a body burden of 409 mg/kg/d
BASF (2009b) Developmental study in rats; read-across from MMA; no effects on development up to 450 mg MMA/kg/d, equivalent to 387 mg/kg/d MAA
Additional information

Data availability:

Regarding developmental toxicity, there is an OECD 414 study on MAA and rabbit data can be obtained by read-across from MMA. No further testing is proposed.

Non-human data

The OECD SIAR concluded that: “Methacrylic acid (MAA), the common metabolite for all the esters, also was tested in groups of 19-25 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 (0, 179, 358, 716 and 1076 mg/m3) and produced no embryo- or foetal lethality, nor foetal malformations after exposure with MAA at any concentration, despite overt maternal toxicity (decreased body weight and feed consumption) at 300 ppm (1076 mg/m3). The NOAEL for developmental toxicity was considered 300 ppm (1076 mg/m3) MAA (Saillenfait et al., 1999).”

For the second species there are no data for MAA, hence data are obtained by read-across from MMA. Since the ESR and the OECD review another study with MMA has been performed, an oral OECD 414 study in rabbits at 50, 150 , and 450 mg/kg/d. The no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 450 mg/kg bw/d. No adverse foetal findings of toxicological relevance were evident at any dose, even in the presence of maternal toxicity (BASF, 2009b).

Human data

No reliable data available for any members of the category.

Justification for classification or non-classification

In the absence of specific reproductive toxicity and by analogy to MMA, MAA is not regarded as toxic to reproduction.