Registration Dossier

Administrative data

Description of key information

The repeat dose toxicity of isoamylene has been determined by testing of its main constituent, 2-methyl-2-butene (2M2B), which produced some general systemic effects in rats following repeated exposure.  These effects were slight and were most apparent in the high dose animals and only to a small extent in the mid-dose animals. The No Observed Effect Concentration was 1665 mg/m3 (580 ppm).

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
1 665 mg/m³

Mode of Action Analysis / Human Relevance Framework

Additional information

Oral

No animal or human data are available

Dermal

No animal or human data are available

Inhalation

Animal data

In a combined repeat dose/reproductive/developmental study (OECD 422; HLS, 2004) on 2 -methyl-2 -butene (2M2B; the main component of isoamylene), rats were exposed (whole body) via inhalation to 580, 2000 and 7000 ppm (1665, 5740 and 20090 mg/m3).  For the repeated dose phase of the study the exposures were for 6 hr/day, 7 days/week for 28 days. 

Bodyweight gain was slightly reduced at the top dose. Slightly longer clotting times were reported at 2,000 ppm (prothrombin time for females) and 7,000 ppm (prothrombin times for both sexes and activated partial thromboplastin times for males). Cholesterol levels were increased among the females exposed to 7,000 ppm, but in the absence of any further effects in the clinical chemistry parameters or the males this finding was considered to be of uncertain biological significance.  In the high-dose females pathological changes were reported in the liver, with associated increased organ weight and some minor hypertrophy of centrilobular hepatocytes.  There was also a decreased incidence of extramedullary hematopoiesis in the spleen in the high dose animals and an increase in goblet cell hyperplasia in the nasal passages of the high dose males.  In addition, a slight increase in severity of myocardial inflammatory heart lesions and in cortical/medullary tubular basophilia in the kidneys was observed in males at ≥2000 ppm. 

General systemic effects were reported in this study, but these effects were slight and primarily in those animals exposed to the highest dose and to a lesser extent to those exposed to 2000 ppm.  Based on these observations the No Observed Effect Level (NOEC) in this study was concluded to be 580 ppm (1,665 mg/m3).

Human data

No data available

Justification for classification or non-classification

Based on the slight general effects seen in this study with a NOAEC at 1665 mg/m3and LOAEC of 5740 mg/m3, in consideration of the criteria of DSD and (i. e. no adverse effects at ≤1000 mg/m3 in 90 day studies and ≤3000 mg/m3 in 28 days studies) no classification of isoamylene for repeat dose effects is warranted.