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Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
352 mg/m³
Study duration:
subchronic
Species:
rat

Additional information

Data availability

There is a 90 d inhalation study for MAA (BASF 2009). There are no studies by other routes and chronic data are absent. The endpoint is satisfied by read-across from MMA.

ORAL

There are no relevant oral repeated dose studies. For assessment purposes the inhalation data are used with appropriate route-to-route extrapolation factors.

DERMAL

There are no relevant dermal repeated dose studies for systemic effects. For assessment purposes the inhalation data are used with appropriate route-to-route extrapolation factors.

The available 3 -week study (Rohm and Haas 1986) is used as supporting information for classification and labelling purposes.

INHALATION

In an OECD 413 guideline study (subchronic inhalation toxicity: 90-day) 10 male and female Sprague Dawley rats per test group were whole body exposed to a vapour of the test substance on 6 hours per working day for 90 days (65 exposures) (BASF, 2008). The target concentrations were 20, 40, 100 and 350 ppm (corresponding to 70, 141, 352 and 1232 mg/m3). A concurrent control group was exposed to conditioned air.

Local effects

At 350 ppm, the local irritating effect (hypertrophy/hyperplasia of the respiratory epithelium in the nasal cavity) was minimal in only 2/10 female animals and represents a LOAEC for local effects. 100 ppm (352 mg/m³) was the NOAEC for local effects in male and female animals.

Systemic effects

There were no adverse systemic findings in any organs including sexual organs, or any changes of sperm mobility and sperm head counts, at the highest dose investigated 350 ppm (1232 mg/m³). Therefore, the no-observed adverse effect level (NOAEC) for systemic organ effects in this study is 350 ppm in male and female rats.

Body weight effects

Methacrylic acid caused reduced food consumption and transiently food efficiency in the high concentration male animals resulting in decreased terminal body weight and body weight gain in these animals. In the absence of any true systemic organ related effects at this dose level these are not considered to be adverse findings. The overall no-observed effect level (NOAEC) for local effects and systemic effects including body weight in this study is 100 ppm for the male and female rats.

In regard to chronic toxicity by inhalation two aspects are not considered to be progressing over time – body weight effects caused by reduced food consumption and nasal lesions caused by local irritation. For true systemic toxicity, data are used by read-across from MMA: 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.

As the no-observed adverse effect level (NOAEC) in the subchronic study on MAA (100 ppm) is below the NOAEC for other systemic effects in the chronic study with MMA it is protective for systemic toxicity and therefore can be used as the basis for the chronic NOAEC.


Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: nose

Justification for classification or non-classification

In a subchronic 90 d inhalation study with MAA there was no indication of severe or irreversible organ effects other than irritation in tissues of the upper respiratory tract at 350 ppm (1232 mg/m³).

Therefore, 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.