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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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