2024/12/22 by Hartwig, Andrea, MAK Commission
#571.95 Toxicology #571.95 Toxikologie #616.9803 Betriebs- und Arbeitsmedizin #616.9803 Industrial and occupational medicine #Butyleneoxide #Butylenoxid #Cyclotetramethylene oxide #Cyclotetramethylenoxid #Diethylene oxide #Diethylenoxid #Entwicklungstoxizität #Furanidin #Furanidine #Hautresorption #Kanzerogenität #Luft #MAK value #MAK-Wert #Oxolan #Oxolane #Spitzenbegrenzung #Tetrahydrofuran #Tetrahydrofurane #Tetramethylene oxid #Tetramethylenoxid #air #carcinogenicity #developmental toxicity #maximale Arbeitsplatzkonzentration #maximum workplace concentration #peak limitation #skin absorption
paper · doi:10.34865/mb10999d9_4ad
The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) summarized and re-evaluated the data for tetrahydrofuran [109-99-9] to derive an occupational exposure limit value (maximum concentration at the workplace, MAK value) considering all toxicological end points. Relevant studies were identified from a literature search and also unpublished study reports were used. Tetrahydrofuran is not irritating to the skin but causes serious eye irritation. The most sensitive effect of tetrahydrofuran in subchronic inhalation studies is a concentration dependent reduced ciliary beat frequency and morphological damage to ciliary cells of the nasal and tracheal mucous membranes at 100 ml/m3 (LOAEC) and above. Concentrations of 200 ml/m3 and above caused adverse liver effects in mice. Based on the LOAEC of 100 ml/m3 for effects on the respiratory tract, a NAEC was extrapolated and after taking into account the increased respiratory volume at the workplace (see List of MAK and BAT values, chapters I b and I c) a MAK value of 20 ml/m3 has been set. As the critical effect is local, Peak Limitation Category I has been assigned with an excursion factor of 2. In developmental toxicity studies concentrations of 5060 and 4934 ml tetrahydrofuran/m3 caused a reduction of body weight gain and a decreased degree of sternebral ossification in the rat foetus; in mice the number of live foetuses was reduced at 1800 ml/m3. Both effects occurred at maternally toxic concentrations and no teratogenic effects were observed. Therefore, tetrahydrofuran remains assigned to Pregnancy Risk Group C. Tetrahydrofuran is not genotoxic. Female B6C3F1 mice developed liver adenomas and carcinomas after long-term-inhalation via a CAR receptor-mediated mechanism leading to enzyme induction and cell proliferation. In comparison with phenobarbital, only a weak activation of the receptor could be demonstrated for tetrahydrofuran. Increased incidences of liver carcinomas were observed only in female mice of this susceptible strain at the highest concentration tested. This concentration already led to elevated mortality in male mice due to toxic effects. In male rats, long-term inhalation of tetrahydrofuran caused renal adenomas which occurred concurrently with a combination of α-2u-globulin nephropathy and chronic progressive nephropathy. Neither mechanism is considered to be relevant to humans. Therefore, tetrahydrofuran has no longer been classified in a Carcinogen Category. Tetrahydrofuran shows no sensitizing potential. Skin contact is expected to contribute significantly to systemic toxicity, thus tetrahydrofuran remains designated with “H”.