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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.8 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):
225
Modified dose descriptor starting point:
NOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert dermal NOAEL to oral NOAEL: 1000 mg/kg/day x (10% dermal absorption/50% oral absorption) = 200 mg/kg/day. Convert oral NOAEL to inhalation NOAEC: 200 mg/kg/day x [1/0.38 x 50/100 x 6.7/10] = 176 mg/m3
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
not applicable for inhalation (differences in species addressed in calculation of dose descriptor starting point.)
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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:
1.1 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):
900
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
other: EC3
Explanation for the modification of the dose descriptor starting point:

Value used for CSA:

 

A.     Qualitative Assessment

The skin sensitization potency based on an EC3 value of 3.9 is considered to be ‘moderate’. Based on ECHA guidance (Chapter R.8 and Part E: Risk Characterization (May, 2016)), moderate skin sensitisers are placed in the moderate hazard band and exposure should be “well-controlled.”

 

B.     Semi-quantitative Assessment

ECHA guidance (Chapter R.8) states that the EC3 value obtained from a LLNA can be used to obtain an induction specific DNEL for sensitization. Based on the formula provided in the ECHA guidance (EC3 X 250 µg/cm2 (to convert to dose per skin area) ÷ AF), the following sensitisation DNELs were determined:

 

·        Worker: 97.5 µg/cm2

·        General population: 39 µg/cm2

 

The assessment factors assigned were as follows:

 

·        Interspecies differences: 2.5 (per ECHA guidance)

·        Intraspecies differences: 5 (worker) or 10 (general population) (per ECHA guidance)

 

 

Additional AFs considered per the ECHA guidance and the publication from which it is based on (Api et al., 2008) are:

·        Vehicle effect: 1 – This AF is assigned if the penetration of the substance may be different compared with the LLNA study conducted. This may be influenced by skin irritation potential as well as formulations/vehicles. The notified substance is formulated in a lubricating mineral oil, which is highly viscous and is unlikely to increase the penetration. In addition, the vehicle used in the LLNA was Acetone-olive oil, which is much more likely (compared to lubricating mineral oil) to enhance penetration and the availability of the substance.

·        Use/exposure considerations: 1 – This factor considers how the product is used and is mostly for cosmetic products (Api, et al., 2008); examples included use under occluded conditions. As the notified substance is not intended for exposure and the frequency of exposure is expected to be minimal, no increase in the AF is warranted.

 

The DNEL values obtained for skin sensitization are consistent with values obtained in the literature:

1.      Publication by Schaafsma et al., (2011) proposes the following limits for a moderate skin sensitiser:

·        Worker: 50 µg/cm2/day

·        Consumer: 25 µg/cm2/day

 

2.      Publication by Griem et al., (2003):

·        10-100 µg/cm2for a moderate potency skin sensitizer

 

3.      ECETOC TRA Report No.93 (2004):

·        100 µg/cm2for moderate sensitisers

 

These literature values demonstrate that the DNEL determined based on the LLNA is reasonable. 

References:

1.      ECHA. Guidance on infromation requirements and chemical safety assessment. Chapter R.8: Characterisation of dose concentration-response for human helath. Version 2.1. November, 2012.

2.      ECHA. Guidance on information requirements and chemical safety assessment. Part E: Risk characterisation. Version 3.0. May, 2016.

3.      Api AM, Basketter, DA, Cadby PA, Cano MF, Ellis G, Gerberick GF, Griem P, McNamme PM, Ryan CA, Safford R. Dermal sensitization quantitative risk assessment (QRA) for fragrence ingredients. Regulatory Toxicology and Pharmacology. 2008.

4.      Schaafsma G, Hertsenber, AJ, Marquart J. Risk assessemnt of local dermal effects and skin sensitisation under the EU chemicals regulation REACH: A proposal for qualitative, exposure scenario specific, approah. Regulatory Toxicology and Pharmacology. 2011.

5.      Griem P, Goebel C, Scheffler H. Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data. Regulatory Toxicology and Pharmacology. 2003.

6.      ECETOC. Targeted risk assessment. Technical report No. 93. 2004

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:
low hazard (no threshold derived)

Additional information - workers

The substance is not expected to be acutely toxic following oral administration or dermal application and therefore acute DNELs for systemic effects are not required. The substance is a skin sensitiser and both a qualitative and semi-quantitative assessment are conducted (see 5.5 for further discussion and background).

Based on the available studies, the substance is considered to not be genotoxic.

In a 28-day dermal toxicity study only local effects but no adverse effects were observed for systemic toxicity and the NOAEL for systemic effects was set at the limit dose of 1000 mg/kg bw/day.

This value was chosen as the starting point for systemic DNELs calculation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 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):
450
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert dermal NOAEL to oral NOAEL: 1000 mg/kg/day x (10% dermal absorption/50% oral absorption) = 200 mg/kg/day. Convert oral NOAEL to inhalation NOAEC: 200 mg/kg/day x [1/1.15 x 50/100] = 87 mg/m3
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Not applicable for inhalation (differences in species addressed in calculation of dose descriptor starting point.)
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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:
0.6 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):
1 800
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available.
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
other: EC3

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 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):
1 800
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAEL Covert dermal NOAEL to oral NOAEL: 1000 mg/kg bw/day x (10% dermal absorption/50% oral absorption) = 200 mg/kg/day
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available.
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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 substance is not expected to be acutely toxic following oral administration or dermal application and therefore acute DNELs for systemic effects are not required. The substance is a skin sensitiser and both a qualitative and semi-quantitative assessment are conducted (see 5.5 for further discussion and background).

Based on the available studies, the substance is considered to not be genotoxic.

In a 28-day dermal toxicity study only local effects but no adverse effects were observed for systemic toxicity and the NOAEL for systemic effects was set at the limit dose of 1000 mg/kg bw/day.

This value was chosen as the starting point for systemic DNELs calculation.