Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
100% absorption is assumed via both routes in both species (ECHA CSA Guidance Chapter R.7c Figure R.7.12-5)
AF for dose response relationship:
1
Justification:
No justification for deviating from the standard AF outlined in Ch R:8 based on the database.
AF for differences in duration of exposure:
2
Justification:
DNEL based on sub-chronic study (90 day). Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
2.5
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for intraspecies differences:
5
Justification:
Standard default value for workers as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Justification:
Reliable study used
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

No adverse effects upon which DNELs for workers could be based have been seen in any of the available toxicity studies. In accordance with ECHA Guidance Document Chapter R.8, therefore, DNELs for acute effects have not been derived. The physico-chemical properties of the substance demonstrate that there is negligible potential for inhalation exposure to the substance; consequently, no inhalation DNELs have been derived. Based on an absence of toxicity in the available studies, a long-term dermal DNEL for systemic effects in workers of 10 mg/kg bw/day is proposed based on the 90-day oral toxicity study in rats in which a NOAEL of 1,000 mg/kg bw/day was identified (the highest dose tested).

Please note: One member of this SIEF has stated that they have two vertebrate studies (OECD 203 and OECD 423) for this substance. However, despite repeated requests for this information, the studies were not provided and the SIEF was frozen on 14th May 2010.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
100% absorption is assumed via both routes in both species (ECHA CSA Guidance Chapter R.7c Figure R.7.12-5)
AF for dose response relationship:
1
Justification:
No justification for deviating from the standard AF outlined in Ch R:8 based on the database.
AF for differences in duration of exposure:
2
Justification:
DNEL based on sub-chronic study (90 day). Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
2.5
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for intraspecies differences:
10
Justification:
Standard default value for general population as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Justification:
Reliable study used
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation required
AF for dose response relationship:
1
Justification:
No justification for deviating from the standard AF outlined in Ch R:8 based on the database.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic (90 day) to chronic. Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
2.5
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for intraspecies differences:
10
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Justification:
Reliable study
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

No adverse effects upon which DNELs for the general population could be based have been seen in any of the available toxicity studies. In accordance with ECHA Guidance Document Chapter R.8, therefore, DNELs for acute effects have not been derived. The physico-chemical properties of the substance demonstrate that there is negligible potential for inhalation exposure to the substance; consequently, no inhalation DNELs have been derived. Based on an absence of toxicity in the available studies, a long-term oral DNEL for systemic effects in the general population and a long-term dermal DNEL for systemic effects in the general population, each of 5 mg/kg bw/day are proposed based on the 90-day oral toxicity study in rats in which a NOAEL of 1,000 mg/kg bw/day was identified (the highest dose tested).

Please note: One member of this SIEF has stated that they have two vertebrate studies (OECD 203 and OECD 423) for this substance. However, despite repeated requests for this information, the studies were not provided and the SIEF was frozen on 14th May 2010.