Registration Dossier
Registration Dossier
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EC number: 611-033-0 | CAS number: 536759-91-8
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.898 mg/m³
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 18
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 88.157 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The DNEL for inhalation exposure for workers is given by the formula: corrected inhalation NOAEC= NOAEL(oral-rat)* 1/sRVrat * (Absorption (oral-rat)/Absorption(inhal-human))* (sRVhuman/wRV) Where SRV is the standard Respiratory Volume and wRV is the worker Respiratory Volume. The default values assumed for these factors are as follows: Absorption(oral-rat)=50%; Absorption(inhal-human) =100%; sRVrat=0.38 m3/kg/d; sRVhuman= 6.7m3 (8hr); wRV=10m3(8hr). NOAEC(corrected)= 100 mg/kg bw/day* (1/0.38 m3/kg/d)*(50%/100%)* 6.7m3 (8hr)/ 10m3(8hr) NOAEC(corrected)= 88.157 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- A NOAEL of 100mg/kg derived for effects in reproduction (viability) has being selected as the point of departure so factor of 1 used.
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 28 day study are derived using an assessment factor of 6 for extrapolation of the study duration to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- In the absence of dermal absorption data, equivalence is assumed. A default allometric scaling factor of 4 between rats and humans is applied based on ECHA guidance for allometric scaling of data from rats to humans. This is already accounted for in the modification of the dose descriptor starting point.
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC reported in 2010 after an extensive review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied
- AF for intraspecies differences:
- 3
- Justification:
- ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for workers is 3 and not 5 as ECHA proposed. See discussion for detailed justification.
- AF for the quality of the whole database:
- 1
- Justification:
- A full Annex VIII dataset is available for this substance, including a combined 28 day/reproductive screening study.
- AF for remaining uncertainties:
- 1
- Justification:
- uncertainties are already included so a factor of 1 is applied
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.389 mg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 72
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The value selected is the lowest NOAEL, derived from the OECD 422 Reproduction/Development toxicity screening study and is based on viability toxicity values.
- AF for dose response relationship:
- 1
- Justification:
- NOEAL being used as the point of departure so factor of 1 used
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 28 day study are derived using an assessment factor of 6 for extrapolation of the study duration to chronic exposure
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- In the absence of dermal absorption data, equivalence is assumed. A default allometric scaling factor of 4 between rats and humans is applied
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC reported in 2010 after an extensive review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied
- AF for intraspecies differences:
- 3
- Justification:
- ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for workers is 3 and not 5 as ECHA proposed. See discussion for detailed justification.
- AF for the quality of the whole database:
- 1
- Justification:
- A full Annex VIII dataset is available for this substance, including a combined 28 day/reproductive screening study
- AF for remaining uncertainties:
- 1
- Justification:
- uncertainties are already included so a factor of 1 is applied
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Summary
The ECHA guidance proposes an assessment factor of 4 for the allometric scaling from rats to humans when calculating oral and dermal DNELs. However, it then proposes an additional factor of 2.5 to cover remaining differences (uncertainties). There is no clear scientific justification for this additional factor. ECETOC in its Guidance on Assessment Factors to Derive a DNEL (2010) reviewed the scientific evidence and concluded that the factor of 4 for rats was sufficient to cover the allometric scaling from rats to humans and any remaining differences are of intra-species rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter-species variability will not be used.
This ECETOC guidance also reviewed the intra-species assessment factors, which ECHA proposed as 5 for workers and 10 for the general population. ECETOC originally proposed in 2003, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intra-species variability, which includes the remaining differences factor of 2.5.
This was confirmed in the ECETOC (2010) Guidance.
After reviewing these proposals, we have adopted the proposal from ECETOC as our default assessment factors but consider possible additional factors on a case by case basis.
In this case we have decided to use an assessment factor of 3 for workers based on the ECETOC Guidance (ECETOC 2010).
References:
ECHA, 2010 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2 December 2010
ECETOC, 2010Guidance on Assessment Factors to Derive a DNEL, Technical Report No.110,ISSN-0773-8072-110 (print),ISSN-2079-1562-110 (online), October 2010
General Population - Hazard via inhalation 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
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:
- no hazard identified
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
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