Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
35.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose the default respiratory volume for the rat corresponding to the daily duration of human exposure is considered in the first step, followed by a correction for the difference between respiratory rates of workers under standard conditions and under light activity in the second step. NAECcorr_inh = oral NOAEL (20) x 1/0.38 m3/kg bw x 6.7 m3/10 m3 = 35.3 mg/m3. Absorption oral (rat) = Absorption oral (human) = 50% (see toxicokinetics assessment for justification). Therefore, NAECcorr_inh = 35.3 x 50/50 = 35.3 mg/m3.
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
1
Justification:
NOAEL obtained in a chronic study so no assessment factor is required.
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling required for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor for good quality database, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Absorption oral (rat) = 50%. Absorption dermal (human) = 20% (see toxicokinetics assessment for justification). Therefore dose descriptor after route to route extrapolation is 20 x 50/20 = 50 mg/kg bw/day.
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
1
Justification:
NOAEL obtained in a chronic study so no assessment factor is required.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat to human), in accordance with REACH Guidance R.8
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The NOAEL value (20 mg/kg bw/day) obtained in a chronic oral study in rats (2 years) was selected as the starting point for deriving the long-term systemic inhalation DNEL and the long-term systemic dermal DNEL. Acute and long-term inhalation local DNELs were not derived because it is considered that derivation from long term systemic effects provides a suitable margin for safety of use.

The substance is classified as a category 1 skin sensitiser, however, no dose response data are available therefore a qualitative risk assessment has been conducted. Acute systemic dermal and inhalation DNELs were not derived because the substance is not classified for acute dermal or inhalation toxicity.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
0.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose, the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hrs exposure of general public). NAECcorr_inh = oral NOAEL (20) x 1/1.15 m3/kg bw = 17.4 mg/m3. Absorption oral (rat) = Absorption oral (human) = 50% (see toxicokinetics assessment for justification). Therefore, NAECcorr_inh = 17.39 x 50/50 = 17.4 mg/m3.
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
1
Justification:
NOAEL obtained in a chronic study so no assessment factor is required.
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling required for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Absorption oral (rat) = 50%. Absorption dermal (human) = 20% (see toxicokinetics assessment for justification). Therefore dose descriptor after route to route extrapolation is 20 x 50/20 = 50 mg/kg bw/day.
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
1
Justification:
NOAEL obtained in a chronic study so no assessment factor is required.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat to human), in accordance with REACH Guidance R.8
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required. Absorption oral (rat) = Absorption oral (human) = 50% (see toxicokinetics assessment for justification)
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
1
Justification:
NOAEL obtained in a chronic study so no assessment factor is required
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat to human), in accordance with REACH Guidance R.8
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The NOAEL value (20 mg/kg bw/day) obtained in a chronic oral study in rats (2 years) was selected as the starting point for deriving the long-term systemic inhalation DNEL, long-term systemic dermal DNEL and long-term systemic oral DNEL. Acute and long-term inhalation local DNELs were not derived because it is considered that derivation from long term systemic effects provides a suitable margin for safety of use.

The substance is classified as a category 1 skin sensitiser, however, no dose response data are available therefore a qualitative risk assessment has been conducted. Acute systemic oral, dermal and inhalation DNELs were not derived because the substance is not classified for acute dermal or inhalation toxicity.