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EC number: 212-084-8 | CAS number: 760-93-0
No data available for MAAH.
Read across data from methacrylic acid, MAA (hydrolysis product and primary metabolite) and methyl methacrylate, MMA (metabolite donor substance; read across justification see attached document):
2 yr drinking water, rats, MMA: NOAEL 2000 ppm = 124/ 164 mg/kg bw/d in males and females
90 d/ OECD 413, rats, MAA: NOAEC 100 ppm (male/female) (= 352 mg/m³ for local effects and unspecific systemic effects to body weight) 2 yr, NTP protocol, rats, MMA: NOAEC 350 ppm (male/female) (= 1232 mg/m³ for systemic effects in target organs other than body weight effects due to reduced food consumption)
A summary of the mortality data for methyl methacrylate is presented below. Dose group (ppm) Male Female Negative (0) 12/25 9/25 6/7 7/25 7/25 60/70 10/25 7/25 2000 12/25 10/25 No statistical differences were noted in the mortality of the animals exposed to methyl methacrylate and those in the control group. A statistically significant decrease in body weight was observed in the first week for the female rats and in weeks one through three in the male rats administered 2000 ppm methyl methacrylate. Water consumption was reduced in the animals from the high-dose group; however, it was reported that this finding tended to regress towards the end of the study. Food consumption was not affected by the administration of methyl methacrylate in the drinking water.
Hematologic values varied within normal ranges in all groups of rats throughout the study, and urine concentrations of protein and reducing substances showed no trends that appeared relatable to treatment.
Organ to body weight ratios obtained at sacrifice of 2-year survivors differed from the controls only in significantly increased kidney ratios in female rats receiving 2000 ppm of methyl methacrylate (controls 0.0082 ± 0.0019; treated 0.0094 ± 0.0011).
Histopathologic findings showed no abnormalities or lesions, in kind or incidence, not explicable on the basis of naturally occurring ones in this strain of rat at this age.
Diet equivalents of the test materials were calculated from the fluid and food consumption data.
In these calculations, corrections were not made for evaporation losses of the test materials from the drinking water, the orders of magnitude of which are given under methods described above (maximum 15%). Allowing for such losses, it would appear that the concentrations of test materials in the drinking water were equivalent to approximately 10, 100, and 3000 ppm in the diet.
A two years toxicity study was performend in 1964 to study the tolerance of animals to chronic ingestion of methyl methacrylate. No relevant effects were observed after exposure of rats in drinking water up to the highest dose tested (2000 ppm, limited by palatability)..
Mortality: No difference in survival between treated and untreated groups.
Site / Lesion
Nasal Cavity /
Olfactory sensory epithelium /
Focal or multifocal fibrosis
No histopathological findings other than local findings in the respiratory tract. Systemic histopathological effects, as for example in the brain in females particularly at 2000 ppm and above in the subchronic range finding study (Batelle, 1980), are absent in this 104 week study.
Body weight: Mean body weight gain was reduced in females at 500 ppm resulting in 6 -11% lower body weights after week 73 and in males at 1000 ppm which were 5 -10 % lower than controls after week 81.
There was no treatment-related increase in tumour incidence.
In this104-week study with groups of 50 animals each, male rats were treated with MMA vapour by whole-body exposure to 500 or 1000 ppm while female rats were exposed to 250 or 500 ppm.
The primary finding was inflammation of rat nasal cavity as well as olfactory epithelial degeneration at all exposure levels in male and female rats. For local effects the LOAEC was 250 ppm in this study while a NOAEC could not be found.
In contrast to the 90 d range finding study with histopathological changes in females at exposures of 1000 ppm and above (Battelle, 1980), no other significant histopathological changes were reported in male and female rats after 104-week exposures to MMA vapour in this study. Based on this a NOEC for systemic effects of 500 ppm is derived.
Male and female rat body weights were lower at the 1000 ppm (5-10%) and 500 ppm (6-11%) exposure levels, respectively, presumably due to reduced food consumption due to nasal irritation and damage of olfactory epithelium. While food consumption was not recorded in this study this association is confirmed by two other studies, the developmental toxicity study with MMA with reduced food consumption and reduced body weight gain at concentrations higher than 99 ppm (Solomon, 1993) and a subchronic inhalation study with methacrylic acid where there was also an association of irritative effects in the nose and reduced food consumption and reduced body weight gain (BASF, 2008). Consequently, reduced body weight gain, while clearly treatment-related - is considered to be secondary to the local effects in the nose and not the result of true systemic toxicity.
In a valid guideline study acc. to OECD 413 ( Subchronic inhalation toxicity: 90 day exposure of rats), methacrylic acid induced signs of general toxicity as indicated by descreased body weight, body weight gain, food consumption and transiently food efficiency in the high concentration male animals. At a concentration as high as 350 ppm (1232 mg/m³), the local irritating effect was marginal, indicated by the hypertrophy/hyperplasia of the respiratory epithelium in the nasal cavity of two female animals. Substance-related changes of the sexual organs were not noted in any of the exposed animals, nor were there any changes of sperm mobility and sperm head counts. Under the current test conditions, the no-observed adverse effect level (NOAEL) for both, local and systemic effects, in this study is 100 ppm (352 mg/m³) for male and female rats.
NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.
There are no studies available for repeated dose toxicity of methacrylic anhydride. As methacrylic anhydride was demonstrated to hydrolyse very fast into methacrylic acid, and methacrylic acid is the hydrolysis product and primary metabolite of methacrylic anhydride, this endpoint is covered by read across to data of methacrylic acid (MAA) or methyl methacrylate (MMA), the metabolite donor substance (see attached read across justification).
MMA: An early 2-year chronic drinking water study with 25 male and 25 female rats administered with 6, 60 and 2000 ppm MMA no adverse effect were observed other than elevated kidney weights without corresponding histopathology in female rats at 2000 ppm (Borzelleca et al., 1964). The NOAEC was reported as 2000 ppm (164 and 124 mg/kg bw/d) in female and male rats.
There are no relevant dermal repeated dose studies for systemic effects. For assessment purposes theoral study is used with the appropriate route-to-route extrapolation factor.
The available 3-week study (Rohm and Haas, 1986) is used as supporting information for classification and labelling purposes.
MMA: The US National Toxicology Program conducted a series of repeat-exposure inhalation toxicity studies of increasing duration 14 weeks and 104 weeks in male and female rats and mice. (Battelle Pacific Northwest Lab., 1980 and NTP; 1986). In the two-year study reduced mean body weights in female rats was observed at 500 ppm (2080 mg/m3) after week 73 but this was likely a consequence of the local nasal lesion and effects on smell and behaviour/appetite rather than any other systemic organ toxicity. The NOAEC for this effect was 250 ppm (1040 mg/m3) in females. After a 14-week inhalation, mice had cellular necrosis in liver and renal cortices > ca. 8.2 mg/L (2,000 ppm) and rats showed splenic follicular atrophy and bone marrow atrophy at ca. 20.8 mg/L (5,000 ppm; Battelle 1980). Malacia and gliosis of the brain in the 14 week range finder to the NTP study (Battelle, 1980) is considered being the relevant systemic effect, which was seen in 5/9 female rats exposed at 2000 ppm and 1/8 females at 1000 ppm. Therefore, the absence of this effect at 500 ppm (2028 mg/m³) in the corresponding 2-year study (NTP) is considered representing the NOAEC for chronic systemic effects of MMA.
Effects on the nasal respiratory tract were seen in studies in rats and mice in studies of 14 weeks Battelle Pacific Northwest Lab (1980a) and 104 weeks duration (NTP; 1986a). Local effects included inflammation of the nasal cavity and were observed in male and female rats at 250ppm (1040 mg/m3) and above. No compound-related effects were observed in the trachea and larynx. A NOAEC could not be established for local effects. (Considering the Reno and NTP studies were both two year inhalations studies using the same strain of rats the NOAEC for systemic effects of 250ppm in females from the NTP study takes precedence).
MAA: In an OECD 413, 90-day vapour inhalation study in Sprague Dawley rats with MAA revealed general toxicity at 350 ppm (1253 mg/m3) in male animals (BASF 2008). Local, marginal irritation of the respiratory epithelium in the nasal cavity was observed in two female animals. No changes in sexual organs or sperm mobility and sperm head counts were noted. The NOAEL was 100 ppm (358 mg/m3) for local irritation effects in male and females The NOAEL for systemic effects based upon reduced body weight gain in the presence of reduced feed intake but no other systemic effects was also 100 ppm (358 mg/m3) in male and females.
Based on the available data, no classification is proposed for chronic specific target organ toxicity (STOT repeated exposure).
The observed irritation is covered by classification as a respiratory irritant (STOT single exposure), category 3 according to CLP (1272/2008/EC) and UN GHS.
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