Registration Dossier

Administrative data

Description of key information

In total five skin irritation studies in rabbits are available for this substance. The results of the skin irritation studies are somewhat equivocal. A harmonized classification according to Annex VI of Regulation (EC) No 1272/2008 has classified this substance as a skin irritating substance.
There are seven different eye irritation tests with rabbits and all of them show, at most, mild signs of ocular irritation. The studies do not trigger classification for eye irritation. At least three studies with human volunteers, that conducted objective and subjective measurements of eye irritation in vapour exposure, concluded that eye irritation could not be attributed to MTBE.
Regarding respiratory tract irritation, the available animal and human data do not give reason to classify MTBE for respiratory tract irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

In total 5 skin irritation studies with rabbits were available for assessment. The results of the skin irritation studies are somewhat equivocal. Three studies were performed according to OECD Guideline 404. However, no sample purity was reported in two of the three studies, so the remaining study, in which also the most effects were observed, was chosen as key study (Hüls, 1985a). Rabbits were subjected to MTBE under occlusive patch for 4 hours (which is a deviation from OECD guideline 404). After the exposure, the residual substance was washed out with water. The results showed one hour after the end of exposure moderate to severe oedema and moderate erythema. The effects lasted the first 8 days of the 14 days of observation. The primary irritation score (PIS) was 5 and 24+48+72-scores were 2.9 for erythema and 2.3 for oedema.

 

Several eye irritation studies were available for assessment. Three of these studies were conducted according to OECD Guideline 405. However, no purity was reported in two of them. Therefore the remaining study (Hüls, 1985b) was chosen as a key study. The right eye of three male and three female rabbits were exposed once to MTBE (without washing, the left eye served as control). The eyes were observed for 1, 24, 48 and 72 hours and 6, 8, 10 and 14 days after treatment. Only slight redness of conjunctiva was observed, with mean average scores at (24+48+72 hr) of 1.3 for conjunctiva and 0.4 for chemosis, the scores for cornea and iris being zero. MTBE was not irritating for the eye.

In addition to the animal studies, also some human data is available. A group of 19 male and 18 female subjects was exposed for one hour to 1.39 ppm (5 mg/m3) MTBE or to clean air (Prah et al., 1994). No significant irritating effect on eyes was found.

Also no eye irritating effects related to MTBE exposure were observed by Cain et al. (1996), who exposed 22 male and 21 subjects for one hour to 1.7 ppm (6 mg/m3) MTBE.

Ten male volunteers were exposed to 5, 25, or 50 ppm MTBE during two hours exercising at 50W on a bicycle ergometer (Nihlén et al., 1998). Subjective eye ratings and objective eye measurements showed no relation to MTBE exposure.

 

Regarding respiratory tract irritation, mice were exposed to 300, 1000, 3000, 10000 and 30000 mg/m3 MTBE for one hour (single exposure) (Tepper et al, 1994). A 50% respiratory rate decrease was predicted by linear regression interpolation to occur at 16600 mg/m3. Slight to severe sensory irritation occurred at all concentrations. There were signs of pulmonary irritation indicative of lung injury at the highest concentration. However, results of the performed lung lavage measurements did not support this observation.

In the available acute inhalation toxicity study with male Sprague Dawley rats conducted by ARCO Chemical Company (1980b), general signs of upper respiratory tract irritation were seen at 70 and 230 mg/l MTBE (single exposure for 4 hours).

The inhalation repeated dose studies with rats and mice do not trigger a concern for respiratory tract irritation.

In addition to the animal data, also some human data is available. A group of 19 male and 18 female subjects was exposed for one hour to 1.39 ppm (5 mg/m3) MTBE or to clean air (Prah et al., 1994). No significant irritating effect on respiratory tract was found.

Also no respiratory tract irritation related to MTBE exposure were observed by Cain et al. (1996), who exposed 22 male and 21 subjects for one hour to 1.7 ppm (6 mg/m3) MTBE.

Ten male volunteers were exposed to 5, 25, or 50 ppm MTBE during two hours exercising at 50 W on a bicycle ergometer (Nihlén et al., 1998). MTBE exposure did not cause subjective symptoms of nose irritation and objective measures of nose function as well as markers of mucous membrane inflammation were not significantly related to MTBE.

 

Effects on skin irritation/corrosion:irritating

Justification for classification or non-classification

In total five skin irritation studies in rabbits are available for this substance. The results of the skin irritation studies are somewhat equivocal. A harmonized classification of Skin Irritant Category 2 classification has been specified in EU-CLP (Regulation (EC) No. 1272/2008).

However, as the key skin irritation test was conducted under occlusive conditions the scores recorded were likely higher than would be normally expected under semi-occluded conditions in line with current testing guidelines. This overestimation would explain why in other tests, less irritation was observed and the apparent "equivocal" results were stated. Although the weight of evidence does not justify the existing EU-CLP Skin Irritant Category 2, this classification is obligatory.

Studies in human volunteers at low air concentrations have shown no signs of eye irritation. Based on the scores from animal studies MTBE is not considered an eye irritant. In accordance with EU-CLP (Regulation (EC) No. 1272/2008), classification for eye irritation is not necessary based on the available data.

The results from the animal studies and the experience in human volunteers do not give reason to classify MTBE as a respiratory irritant.