Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.73 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):
75
Dose descriptor starting point:
NOAEL
Value:
83.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
205 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to REACH guidance R.8, the NOAEL of 83.33 mg/kg bw/day corresponds to a workplace NAEC of 205 mg/m³:

It is assumed, that inhalation absorption is comparable to oral absorption.

Procedure a) 83.33 mg/kg bw/day : 4 (allometric scaling) x 70 kg bw (body weight human) : 10 m3 (human respiratory volume per 8 h shift) x 7/5 (7 days/week exposure in key study to 5 days working week) = 204.16 mg/m³

Procedure b) 83.33 mg/kg x d : 0.38 m³/kg bw (8 h respiratory volume, rat) x 6.7/10 (correction to human respiratory volume per 8 h shift) x 7/5 (7 days/week exposure in key study to 5 days working week) = 205.69 mg/m³

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Extrapolation factor from subacute exposure to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Already considered in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
medium hazard (no threshold derived)
DNEL related information
Justification:
Default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
483.3 µg/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):
150
Dose descriptor starting point:
NOAEL
Value:
83.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
72.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to REACH guidance R.8, the NOAEL of 83.3 mg/kg bw/day corresponds to a NAEC of 72.5 mg/m³

It is assumed, that inhalation absorption is comparable to oral absorption.

Procedure a) 83.3 mg/kg bw/day : 4 (allometric scaling) x 70 kg bw (body weight human) : 20 m³ (daily human respiratory volume) = 72.89 mg/m³

Procedure b) 83.3 mg/kg bw/d : 1.15 m3/kg bw (24 h respiratory volume, rat) = 72.43 mg/m³

Exposure in key study was on 7 days/week

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default for extrapolation factor from subacute exposure to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Already considered in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
no hazard identified
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
139 µg/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):
600
Dose descriptor starting point:
NOAEL
Value:
83.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
83.3 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default for extrapolation from subacute exposure to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor of 4 from rat to humans
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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

There is no direct consumer exposure, only a potential exposure via the environment has to be considered.