Registration Dossier
Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 205-575-3 | CAS number: 142-96-1
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 13 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other:
- Overall assessment factor (AF):
- 25.5
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 335 mg/m³
- AF for differences in duration of exposure:
- 3.4
- Justification:
- Minimal toxicological profile justifies factor of 3.4 to extrapolate from sub-acute to chronic exposure
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not applicable for inhalation
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 3
- AF for the quality of the whole database:
- 1
- Justification:
- Multiple reliable guideline studies are available with consistent results
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:
- 4 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- other:
- Overall assessment factor (AF):
- 102
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 400 mg/kg bw/day
- AF for differences in duration of exposure:
- 3.4
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 3
- AF for the quality of the whole database:
- 1
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
DNELs for Acute (local and systemic) and Repeated exposure (Local):
These DNELs are not relevant for this substance. The acute toxicity values are in excess of 21'000 mg/m3 (inhalation) and 7'000 mg/kg bw (oral and dermal) and in the acute inhalation toxcity study (and repeated dose inhalation study) there was no evidence of narcotic effects at any dose level. As such acute exposure scenarios for this substance are not considered relevant. In addition, the substance is not irritating to the eyes, skin or respiratory tract and therefore there are no data on which to base DNELs for local effects.
DNELs Repeated dose inhalation and dermal
Key study selection:
In the repeated dose toxicity section there are three studies available: a 28-day oral study that was not performed specifically to the OECD guideline, but had a specific focus on testicular toxicity. In addition, two inhalation studies are available conducted according to the standard OECD guidelines for the 28-day and 90-day studies and under GLP. In the oral study, although the study was not to the specific guideline, it was thorough in its assessment of systemic toxicity and reported a NOEL of 200 mg/kg bw/day.
The lowest observed NOEC was 500 mg/m3 for the female rats obtained in the 28-day inhalation study. The 'adjusted starting point' for the inhalation DNEL is 500 mg/m3 * 6.7/10 = 335 mg/m3.
For the oral DNEL, the adjusted starting point = 200/0.38 * 6.7/10 = 352 mg/m3. The oral study will also be used for the dermal DNELs (since route to route extrapolation from oral to dermal is marginally more reliable than inhalation to dermal).
Inhalation DNEL, repeated exposure, systemic toxicity:
Revised starting point = 335 mg/m3
Assessment factors:
Allometric scaling = not applicable
'Other differences' = 2.5
Duration = 3.4 - based on the publication from Batke et al 2011 (Toxicology Letters 205, 122 -129) an analysis of repeated dose toxicity studies demonstrates that a factor of 3.4 is acceptable in the majority of cases to extrapolate from a subacute study to the chronic exposure situation. Given the minimal toxicological profile of this substance, deviating from the ECHA default is justified in this case.
Worker variability = 3 - Given the minmial toxicological profile for this substance and the absence of any significant findings in the available studies, a deviation from the ECHA default factor of 5 to the value used by SCOEL and proposed by ECETOC is justified.
quality of database = 1 - multiple reliable guideline studies are available with consistent results.
Total factor: 25.5
Inhalation DNEL = 335 / 25.5 = 13 mg/m3
Dermal DNEL, repeated exposure, systemic toxicity
Revised starting point = 400 mg/kg bw (assuming 50% dermal penetration and 100% oral absorption)
Assessment factors:
Allometric scaling = 4
'Other differences' = 2.5
Duration = 3.4 - based on the publication from Batke et al 2011 (Toxicology Letters 205, 122 -129) an analysis of repeated dose toxicity studies demonstrates that a factor of 3.4 is acceptable in the majority of cases to extrapolate from a sub acute study to the chronic exposure situation. Given the minimal toxicological profile of this substance, deviating from the ECHA default is justified in this case.
Worker variability = 3 - Given the minmial toxicological profile for this substance and the absence of any significant findings in the available studies, a deviation from the ECHA default factor of 5to the value used by SCOEL and proposed by ECETOC is justified.
quality of database = 1 - multiple reliable guideline studies are available with consistent results.
Total factor = 102
Dermal DNEL = 400/102 = 4 mg/kg bw (rounded up)
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
No consumer DNELs calculated due to the lack of consumer or general population exposure scenarios.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
