Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Value:
1 311.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr = NOAELdermal*(1/0.38 m³/kg bw/day)*(ABSdermal-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 1488 mg/kg bw/day*(1/0.38 m³/kg bw/day)*(0.5/1)*0.67 = 1311.8 mg/m³. Due to the absence of route-specific information on the starting (dermal) and end (inhalation) route, a worst case approach has to be made assuming a limited absorption for the starting route (dermal) and a maximum absorption for the end route (inhalation). By default, the oral absorption rate is considered to be half of that of the inhalation absorption. Since dermal absorption is generally considered to be as high as oral absorption, it is thus assumed that dermal absorption rate is 50% of that of inhalation absorption (factor: 0.5/1). ABSdermal-rat=dermal absorption rate in rats, ABSinh-human=inhalation absorption rate in humans.
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF for workers
AF for the quality of the whole database:
1
Justification:
The selected study is the most adequate and reliable study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.96 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
1 488 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation is required.
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-day study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF for workers
AF for the quality of the whole database:
1
Justification:
The selected study is the most adequate and reliable study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

SUBSTANCE-TAILORED EXPOSURE DRIVEN TESTING

In accordance with Annex XI, Section 3 of Regulation (EC) 1907/2006, testing in accordance with Sections 8.7 of Annex VIII and/or IX was omitted, based on the exposure scenario(s) developed in the Chemical Safety Report, meeting the criteria set out in Annex XI Section 3.2(a).

In particular, in accordance with Annex XI Section 3.2 (a)(ii), the manufacturer or importer shall demonstrate and document that following condition is also fulfilled:

“a DNEL or a PNEC can be derived from results of available test data for the substance concerned taking full account of the increased uncertainty resulting from the omission of the information requirement, and that DNEL or PNEC is relevant and appropriate both to the information requirement to be omitted and for risk assessment purposes”

As required under Regulation (EC) 1907/2006, Annex XI, 3.2 (a)(ii), the appropriate DNELs were derived using the available data, and applied to derive Risk Characterisation Ratios (RCRs).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
646.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr = NOAELdermal*(1/1.15 m³/kg bw/day)*(ABSdermal-rat/ABSinh-human) = 1488 mg/kg bw/day*(1/1.15 m³/kg bw/day)*(0.5/1) = 646.9 mg/m³. Due to the absence of route-specific information on the starting (dermal) and end (inhalation) route, a worst case approach has to be made assuming a limited absorption for the starting route (dermal) and a maximum absorption for the end route (inhalation). By default, the oral absorption rate is considered to be half of that of the inhalation absorption. Since dermal absorption is generally considered to be as high as oral absorption, it is thus assumed that dermal absorption rate is 50% of that of inhalation absorption (factor: 0.5/1). ABSdermal-rat=dermal absorption rate in rats, ABSinh-human=inhalation absorption rate in humans.
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
1
Justification:
The selected study is the most adequate and reliable study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
1 488 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation is required.
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-day study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
1
Justification:
The selected study is the most adequate and reliable study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
1 488 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAELcorr = NOAELdermal*(ABSdermal-rat/ABSoral-human) = (1488 mg/kg bw/day)*(1/1) = 1488 mg/kg bw/day. It is assumed that the dermal absorption rate is 100% of that of the oral absorption according to ECHA CSA Guidance Chapter R.7c Figure R.7.12-5. ABSdermal-rat = dermal absorption rate in rats, ABSoral-human = oral absorption rate in humans.
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-day study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
1
Justification:
The selected study is the most adequate and reliable study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

SUBSTANCE-TAILORED EXPOSURE DRIVEN TESTING

In accordance with Annex XI, Section 3 of Regulation (EC) 1907/2006, testing in accordance with Sections 8.7 of Annex VIII and/or IX was omitted, based on the exposure scenario(s) developed in the Chemical Safety Report, meeting the criteria set out in Annex XI Section 3.2(a).

In particular, in accordance with Annex XI Section 3.2 (a)(ii), the manufacturer or importer shall demonstrate and document that following condition is also fulfilled:

“a DNEL or a PNEC can be derived from results of available test data for the substance concerned taking full account of the increased uncertainty resulting from the omission of the information requirement, and that DNEL or PNEC is relevant and appropriate both to the information requirement to be omitted and for risk assessment purposes”

As required under Regulation (EC) 1907/2006, Annex XI, 3.2 (a)(ii), the appropriate DNELs were derived using the available data, and applied to derive Risk Characterisation Ratios (RCRs).