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
DNEL related information
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
DNEL value:
250 mg/m³
AF for differences in duration of exposure:
6
AF for other interspecies differences:
5
AF for intraspecies differences:
2.5
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
225
Dose descriptor:
NOAEC
DNEL value:
25 mg/m³
AF for dose response relationship:
3
Justification:
LOAEC to NOAEC conversion
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
5
AF for intraspecies differences:
2.5
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62.5 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 500 mg/kg bw/day
AF for interspecies differences (allometric scaling):
5
AF for intraspecies differences:
6
Justification:
intra species 2.4*2.5 (rabbit*additional)
AF for the quality of the whole database:
2
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The potential for short-term high level (i.e. peak) exposure is low with regard to the test substance. Therefore it is expected that the DNELlongterm is sufficient protective for short-term exposure to the test substance.

For local dermal effects no NOAEL could be derived based on the data available. The data on humans were insufficient to confirm that the test substance induces contact urticaria. The substance is not a skin irritant. Therefore no DNEL for local effects via the dermal route was derived. In order to allow the DNEL for systemic effects to be sufficiently protective for local effects as well, an additional safety factor of 2 to account for the uncertainties in the database related to local effects was included.

Based on the outcome of the oral repeated dose studies with the structural analogue sodium bezoate, it can be concluded that duration of exposure did not influence the height of the NOAEL. The NOAEL is ca. 1000 mg/kg bw after 10 days, 35 days, 90 days and after 2 years. In the chronic toxicity study (Sodemoto, 1979) with the test substance that is taken as starting point for the derivation of the DNEL no effects were reported at the highest dose tested which was 1000 mg/kg bw. For systemic effects after dermal exposure no relation between effect level and exposure duration is expected. For inhalation exposure, where local effects are available, it cannot be excluded that local effects on the respiratory tract will become more severe after prolonged exposure and concomitant systemic effects may aggravate with increased local lesions.

Therefore for the calculation of the oral and dermal DNEL no assessment factor is added for exposure duration, but for inhalation exposure the standard assessment factor of 6 (subacute to chronic) is taken into account.

For dermal exposure the DNEL seems to be much higher than that for oral exposure (see under general population). This can be explained through the limited uptake of the test substance via the skin (50%).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/m³
DNEL related information
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
DNEL value:
250 mg/m³
AF for differences in duration of exposure:
6
Justification:
Subacute to Chronic
AF for interspecies differences (allometric scaling):
10
AF for intraspecies differences:
2.5
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.06 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
450
Dose descriptor:
LOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
31.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 500 mg/kg bw/day
AF for interspecies differences (allometric scaling):
10
AF for intraspecies differences:
6
Justification:
2.4*2.5 (rabbit*additional)
AF for the quality of the whole database:
2
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.6 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
AF for interspecies differences (allometric scaling):
10
AF for intraspecies differences:
6
Justification:
2.4*2.5 (rabbit*additional)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

The potential for short-term high level (i.e. peak) exposure is low with regard to the test substance. Therefore it is expected that the DNELlongterm is sufficient protective for short-term exposure to the test substance.

For local dermal effects no NOAEL could be derived based on the data available. The data on humans were insufficient to confirm that the test substance induces contact urticaria. The substance is not a skin irritant. Therefore no DNEL for local effects via the dermal route was derived. In order to allow the DNEL for systemic effects to be sufficiently protective for local effects as well, an additional safety factor of 2 to account for the uncertainties in the database related to local effects was included.

Based on the outcome of the oral repeated dose studies with the analogue substance sodium benzoate, it can be concluded that duration of exposure did not influence the height of the NOAEL. The NOAEL is ca. 1000 mg/kg bw after 10 days, 35 days, 90 days and after 2 years. In the chronic toxicity study (Sodemoto, 1979) with the test substance that is taken as starting point for the derivation of the DNEL no effects were reported at the highest dose tested which was 1000 mg/kg bw. For systemic effects after dermal exposure no relation between effect level and exposure duration is expected. For inhalation exposure, where local effects were found, it cannot be excluded that local effects on the respiratory tract will become more sever after prolonged exposure and concomitant systemic effects may aggravate with increased local lesions.

Therefore for the calculation of the oral and dermal DNEL no assessment factor is added for exposure duration, but for inhalation exposure the standard assessment factor of 6 (subacute to chronic) is taken into account.

For dermal exposure the DNEL seems to be much higher than that for oral exposure (see under general population). This can be explained through the limited uptake of the test substance via the skin (50%).