Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 779 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
DNEL value:
21 240 mg/m³
AF for dose response relationship:
1
Justification:
As the DNEL is based on a NOAEL a dose response factor of 1 was applied per REACH guidance R.8.4.3.1. The study followed OECD guidelines
AF for differences in duration of exposure:
2
Justification:
Per REACH guidance R.8.4.3.1, an assessment factor of 2 is applied to go from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Per REACH guidance R.8.4.3.1, a factor of 1 is supported because allometric scaling is not applicable when an inhalation DNEL is based on an inhalation study.
AF for other interspecies differences:
1
Justification:
Per REACH guidance R.8.4.3.1, a factor of 1 is supported based on the following. Measurement of the blood: air partition coefficient demonstrates the rat will adsorb at least twice the dose of humans. In addition, the DNEL is being derived based on data from the most sensitive species (rat).
AF for intraspecies differences:
3
Justification:
Per REACH guidance R.8.4.3.1 an assessment factor of 3 was applied based on the facts that the substance can be considered as poorly adsorbed, poorly metabolized, rapidly eliminated from the body and should show minimal intraspecies differences in toxicological properties.
AF for the quality of the whole database:
1
Justification:
An extensive database of over 10 high quality toxicology studies are available as noted in the dossier. All studies are modern GLP and OECD (where available).
AF for remaining uncertainties:
1
Justification:
No additional assessement factors are needed as a comprehensive program with all significant endpoints considered.
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:
hazard unknown (no further information necessary)
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

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:
379 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
21 240 mg/m³
AF for dose response relationship:
1
Justification:
As the DNEL is based on a NOAEL a dose response factor of 1 was applied per REACH guidance R.8.4.3.1. The study followed OECD guidelines
AF for differences in duration of exposure:
2
Justification:
Per REACH guidance R.8.4.3.1, an assessment factor of 2 is applied to go from sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Per REACH guidance R.8.4.3.1, a factor of 1 is supported because allometric scaling is not applicable when an inhalation DNEL is based on an inhalation study.
AF for other interspecies differences:
1
Justification:
Per REACH guidance R.8.4.3.1, a factor of 1 is supported based on the following. Measurement of the blood: air partition coefficient demonstrates the rat will adsorb at least twice the dose of humans. In addition, the DNEL is being derived based on data from the most sensitive species (rat).
AF for intraspecies differences:
5
Justification:
Per REACH guidance R.8.4.3.1 an assessment factor of 5 was applied based on the facts that the substance can be considered as poorly adsorbed, poorly metabolized, rapidly eliminated from the body and should show minimal intraspecies differences in toxicological properties.
AF for the quality of the whole database:
1
Justification:
An extensive database of over 10 high quality toxicology studies are available as noted in the dossier. All studies are modern GLP and OECD (where available).
AF for remaining uncertainties:
1
Justification:
No additional assessement factors are needed as a comprehensive program with all significant endpoints considered.
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:
hazard unknown (no further information necessary)
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:
109 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
4 362 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No oral toxicity data are available. The NOAEL from the 90-day repeated-dose inhalation toxicity study in rats is used for derivation of the DNEL-long-term for the oral route.
AF for dose response relationship:
1
Justification:
As the DNEL is based on a NOEL a dose response factor of 1 was applied per REACH guidance R.8.4.3.1. The study followed OECD guidelines
AF for differences in duration of exposure:
2
Justification:
Per REACH guidance R.8.4.3.1, an assessment factor of 2 is applied to go from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Per REACH guidance R.8.4.3.1, a factor of 4 for allometric scaling from rat to human is used
AF for other interspecies differences:
1
Justification:
Per REACH guidance R.8.4.3.1, a factor of 1 is supported based on the following. Measurement of the blood: air partition coefficient demonstrates the rat will adsorb twice the dose of humans.
AF for intraspecies differences:
5
Justification:
Per REACH guidance R.8.4.3.1 an assessment factor of 5 was applied based on the facts that the substance can be considered as poorly adsorbed, poorly metabolized, rapidly eliminated from the body and should show minimal intraspecies differences in toxicological properties.
AF for the quality of the whole database:
1
Justification:
An extensive database of over 10 high quality toxicology studies are available as noted in the dossier. All studies are modern GLP and OECD (where available).
AF for remaining uncertainties:
1
Justification:
No additional assessement factors are needed as a comprehensive program with all significant endpoints considered.
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