Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Dose descriptor starting point:
NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL

Workers - Hazard for the eyes

Additional information - workers

3-Methyl-2-butenal is a strongly irritating alpha-beta-unsaturated aldehyde. However, it appears to be less reactive and less cytotoxic than other alpha-beta-unsaturated aldehydes like acroleine (2-propenal) and crotonaldehyde (2-butenal) and to share some similariaties with aliphatic aldehydes.

The NOAEC in the frame of a rat 28-day inhalation study was 30 ppm (100 mg/m3). Acroleine showed irritation in humans as low as 0.1 ppm and increased cell proliferation rates in rat nose at 0.2 and 0.6 ppm. This difference appears to be explainable by the two methyl group substitutions at the double bound, which almost prevents a Michael reaction with proteins, DNA and other biological molecules. On the other hand, some alkylating properties via other mechanisms or after biotransformation cannot be totally excluded, also in the light of a positive bacterial mutation assay.

There is no information on carcinogenicity and on local genotoxicity at the port of entry. Hence, in the case of this aldehyde, it should be stated, that a time extrapolation factor is almost negligible. On the contrary, a time extrapolation factor of 6 is proposed. The allometric factor is 1 due to the inhalation route. Furthermore, an intraspecies variation factor of 5 is proposed. This leads to a chronic DNEL for workers of 1 ppm (3 mg/m3) which is regarded as equal for local and systemic effects and is also valid for acute exposure.

For systemic dermal exposure it is assumed that the systemic internal dose after resorption from the intestinal tract and skin is similar (which is a very approximate assessment). The LOAEL in the 18-week oral study (OECD 415) was the top dose (77 mg/kg b.w.); reduced water and food intake and glandular stomach mucosa erosion/ulceration were observed (NOAEL = 21 mg/kg b.w.). The allometric factor is reduced to 2 since local effects were observed. The NOAEL is also divided by a time extrapolation factor of 2 (for chronic exposure) and an intraspecies factor of 5, which results in a dermal DNEL of 1 mg/kg b.w. for chronic exposure and 2 mg/kg/day for short-term exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Dose descriptor starting point:
NOAEC

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Additional information - General Population

For the general population, the chronic DNEL is divided by 2. The oral DNEL is taken from the drinking water study.