Toxicological evaluation and limit values for Methyl-tertiary-butyl ether (MTBE), Formaldehyde, Glutaraldehyde, Furfural

3. Human toxicity

Inhalation

In a chamber exposure study 10 volunteers were exposed during the performance of light physical exercise to 18, 90 and 180 mg/m³ MTBE for 2 hours. Subjective ratings (discomfort, irritative symptoms, CNS effects) and eye measurements (redness, tear film break-up time, conjunctival damage, blinking frequency) and nose measurements (peak expiratory flow, acoustic rhinometry, inflammatory markers in nasal lavage) indicated no or minimal effects of MTBE. However, the ratings of solvent smell increased dramatically by entering the chamber (Johanson et al. 1995).

In another laboratory experiment, 37 volunteers were exposed twice to either clean air or 5 mg/m³ of MTBE for 1 hour. The exposure level was chosen to mimic a realistic exposure level during refuelling a car. Some of the exposed persons experienced bad air quality when exposed to MTBE, however, no increase in symptoms with regard to headache and irritation and other parameters of well-being were observed. No changes in performance was observed in neurobehavioural tests. There were no effects with respect to tear film break, ocular hyperaemia, and in different cytologic markers of ocular and nasal inflammation. In an odour test, a threshold (50% of the persons detecting an odour) in water was found to 0.18 mg MTBE/l (Prah et al. 1994).

In a further study, 43 subjects were exposed to 6 mg/m³ for one hour (the exposure was indicated as a realistic high-level-exposure for commuters). No effects were registered with respect to subjective symptoms, discomfort, various ocular parameters, neurobehavioural performance, and inflammation responses of mucous membranes. The average odour detection level was determined to 0.19 mg/m³ (Cain et al. 1994 cited by IPCS 1996).

In thirteen male volunteers exposed to 0, 90, and 270 mg/m³ for one and three hours, significant effects consisting of feeling of heaviness in the head and mucous membrane irritation was observed at the highest exposure level. No altered performance was found in reaction time test and body sway test (ECETOC 1997).

Several health complaints were reported in Alaska, after the introduction of 15% MTBE gasoline during the winter months. The reportings included symptoms such as headache, eye irritation, burning sensation of the nose or throat, nausea or vomiting, dizziness, sensations of spaciness or disorientation, diarrhoea, fever, sweats, muscle aches, fatigue, difficulty in breathing, skin irritation, and fainting. The effects were of short duration and were reported to be worse at temperatures below -18^oC (IPCS 1996).

These reportings are not further described and evaluated in this document because the relation between these unspecific effects and MTBE exposure could not be substantiated. Furthermore, the studies by Prah et al. 1994 and Cain et al. 1994 (described above) were conducted with the aim to disclose relation between the mentioned effects and low level MTBE exposure. However, no effects from MTBE exposure were observed in these well-designed studies. Furthermore, ambient air in cities contain many other respiratory irritants including the photooxidation products of MTBE, and therefore the relationship to MTBE can not be confirmed.

Occupational exposure

Workers adding MTBE to gasoline complained of headaches and nausea. During the process that lasted about 20 minutes maximum values of 6.8-13 mg/m³ MTBE were measured (IPCS 1996). [Elevated levels of gasoline vapours have most probably occurred at the same time].

During barge open loading, MTBE exposure exceeding 360 mg/m³ has caused some workers to complain of odour, nausea, headache and respiratory tract irritation (Wibowo 1994).

In a cross-sectional cohort study, 115 garage workers from a region

using 15% MTBE in the winter season were compared to 122 garage workers in a region where the winter time use of 15% MTBE had ceased 10 weeks before. Active air samples and passive sampling confirmed higher MTBE exposure level of the first group, however, no significant differences were found in the reporting of subjective symptoms (registered by the use of questionnaires) between the groups. Also among a subgroup of fuellers pumping gasoline more than 5 hours per day, no differences were registered (Mohr et al. 1994).

Other routes of exposure

In medicine 1-15 ml of MTBE may be administered by instillation into the gallbladder for dissolving gallstones. Mild complications typically include nausea, vomiting, and pain associated with infusion. Additional effects include signs of transient central nervous system sedation, gastrointestinal irritation, evidence of necrosis in the liver and gall bladder, transient cardiovascular effects such as hyper- or hypotension and palpitations, and transient leucocytosis (IPCS 1996)