Registration Dossier

Administrative data

Description of key information

MTBE exhibits low acute toxicity via oral, dermal and inhalation in humans and test animals. In rats, the average oral LD50 is about 4000 mg/kg bw. The dermal LD50 is over 2000 mg/kg bw in rats and over 10000 mg/kg bw in rabbits.

For inhalation, an LC50 of approximately 85 mg/l has been determined. In animals, the most typical effect at high exposures is decreased ability for muscle coordination and hypoactivity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
85 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Three acute oral toxicity studies with rats are available for assessment, all leading to the same conclusion. Out of these studies, the study performed according to OECD Guideline 401 was chosen as a key study (RBM, 1996a). In this study, 5 male and female rats were exposed by gavage with 2000 mg/kg bw MTBE. No deaths occurred. The LD50 value in rats was determined to be > 2000 mg/kg bw. Animals showed hunching and piloerection starting from 2-4 hours after gavage, which disappeared within 2-6 days.

 

Two inhalation toxicity studies with rats have been located. Although none of the studies was performed according to the current guidelines, they both were found to be reliable and the study with the lowest determined LC50 value was chosen as a key study (Industrial Bio-test Laboratories, Inc, 1969b). Five female and five male per group albino rats were exposed to MTBE vapour at 44, 65, 86, 99, 167 and 395 mg/l for 4 hours. The clinical signs included ataxia, tremors, lacrimation, clonia, unconsciousness and hyperactivity. Surviving animals appeared normal the morning after exposure. In the 86 mg/l group, six animals died and in the higher dose groups, all animals died. Necropsy of the animals which died revealed slight to moderate hyperemia in the lungs. The animals that survived the 14-day observation period had minimal to mild lung hyperemia. An LC50 value of 85 mg/l/4h was calculated based on the results of this study.

 

Three acute dermal toxicity studies, one with rats and two with rabbits, were available for assessment, all leading to the same conclusion. Out of these studies, the rat limit test (RBM, 1996b) was chosen as a key study. Animals were exposed via the dermal route to 2000 mg/kg bw under occlusion. No animals died and neither general clinical signs nor behavioural alterations were observed in any treated rat during the observation period. At the treatment site slight erythema was noted in 4 animals during the first 8 hours after the 24 hours exposure period. Based on the results of the test, the LD50 value in rats was determined to be > 2000 mg/kg bw.

Human male volunteers reported mild symptoms, mainly feelings in the head and feeling less cheerful (FIOH, 1997). The frequency of symptoms was related to the exposure level (0, 25, 75 ppm) and reached statistical significance at 75 ppm after 3 hours of exposure to MTBE. These effects were rated as slight. There was no indication found of an objective sign of CNS function impairment in terms of psychomotor performance, sustained attention, or standing steadiness. This study suggests a LOAEC of 75 ppm. It should be noted that although sensory symptoms may show greater sensitivity than objective indices, it is possible that symptoms are mediated by mechanisms other than CNS depression, especially as MTBE has an unpleasant odour.

Another human volunteer study investigated whether CNS effects occurred after exposure up to 50 ppm MTBE for two hours while the persons were exercising at 50W on a bicycle ergometer (Nihlen, 1998). Effects were measured by a questionnaire. No indications for the occurrence of CNS effects were reported. The study results suggested a NOAEC of 50 ppm.

The SCOEL considered these two human volunteer studies, which show only mild symptoms at 75 ppm after 3 hours exposure, as key in case of acute toxicity of MTBE and derived a 15-min short-term occupational exposure limit (STEL) of 100 ppm using the results of these studies.

Justification for classification or non-classification

In rats, the LD50 figure of the acute oral toxicity key study was >2000 mg/kg bw. The LD50 values of the two supporting studies were 3800 and 3866 mg/kg bw/day, respectively. The dermal LD50 is over 2000 mg/kg bw in rats and over 10000 mg/kg bw in rabbits. For inhalation, an LC50 of approximately 85 mg/l has been determined.

In accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not required for acute toxicity based on the available data.