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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.75 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:

Step 1) Relevant dose-descriptor; Value: 1000 mg/kg bw/day (NOAEL); Remark: This is the concentration where no significant adverse effects were seen in a sub-chronic oral toxicity study. 

Step 2) Modification of starting point for rat respiratory volume (Allometric scaling); Value: 0.38 m3/kg bw (rat 8-hour respiratory volume); Remark: A modification of starting point for rat respiratory volume was applied per REACH guidance R.8.4.2. 

Step 3) Modification of starting point for differences in respiratory volumes;Value: 0.67 (6.7 m3/10 m3); Remark: A modification was applied to account for the increased respiratory volumes in active workers as compared to individuals at rest per REACH guidance R.8.4.2. 

AF for dose response relationship:
1
Justification:
A factor of 1 is appropriate since the dose descriptor is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
This is a default assessment factor for a sub-acute study per REACH Guidance R.8.4.3.1.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted start point was via mg/m3(inhalation) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
5
Justification:
This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
AF for remaining uncertainties:
2
Justification:
A factor of 2 is appropriate per REACH guidance R.8.4.2 (oral to inhalation).
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:
3.33 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):
300
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

This is the concentration where no significant adverse effects were seen in a repeated dose oral toxicity study. 

AF for dose response relationship:
1
Justification:
A factor of 1 is appropriate since the dose descriptor is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
This is a default assessment factor for a sub-acute study per REACH Guidance R.8.4.3.1.
AF for interspecies differences (allometric scaling):
4
Justification:
A factor of 4 is appropriate since the adjusted start point was via mg/kg per REACH guidance 8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
5
Justification:
This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
AF for remaining uncertainties:
1
Justification:
A factor of 1 is appropriate since the animal exposure was via ingestion per REACH guidance 8.4.2.
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:
DNEL (Derived No Effect Level)
Value:
75 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
other: EC3
AF for dose response relationship:
3
Justification:
A factor of 3 is appropriate as an EC3 value can be considered as a LOAEL for induction of skin sensitization per REACH R.8 Appendix R.8-10.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since local effects are independent of the basal metabolic rate, and the adjusted start point was via µg/cm2(dermal) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
10
Justification:
A default factor of 10 is appropriate per REACH guidance 8.4.3 and Appendix R8-10.
AF for intraspecies differences:
5
Justification:
This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
AF for remaining uncertainties:
1
Justification:
A factor of 1 is appropriate since the animal exposure was via the dermal route per REACH guidance 8.4.2.

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Potential worker exposure would likely occur via the dermal or inhalation routes.

Based on the rat acute oral and dermal LD50 values of >5000 mg/kg and the 4-hour LC50 in rats of >0.89 mg/L (the maximum practically attainable atmospheric aerosol concentration), this substance is not classified for acute toxicity via the oral, dermal, or inhalation routes under REACH regulations and guidance. 

Male and female rats were exposed to the test substance daily via gavage in an OECD 422 study (oral toxicity with one generation reproduction screening study) at doses of 100, 300, and 1000 mg/kg. No evidence of systemic toxicity was observed at the highest dose tested, therefore the NOAEL was 1000 mg/kg. 

Although the weight of evidence suggests that this test substance is not a skin sensitizer, and the substance is not classified as a skin sensitizer, effects were produced in an acute exposure LLNA study; therefore a short-term DNEL for local effects by the dermal route was derived.

In a local lymph node assay, this substance was found to be positive for dermal sensitization with an EC3 value of 45% (11250 µg/cm2). As per REACH R.8 Appendix R. 8-10 Skin sensitization, an EC3 value can be considered as a LOAEL for induction (expressed in µg/cm2) and can be used for development of a short-term DNEL for local effects.

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:
DNEL (Derived No Effect Level)
Value:
1.67 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

This is the concentration where no significant adverse effects were seen in a repeated-dose oral toxicity study. 

AF for dose response relationship:
1
Justification:
A factor of 1 is appropriate since the dose descriptor is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
This is a default assessment factor for a sub-acute study per REACH Guidance R.8.4.3.1.
AF for interspecies differences (allometric scaling):
4
Justification:
A factor of 4 is appropriate since the adjusted start point was via mg/kg per REACH guidance 8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
This is a default assessment factor for the general population per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
AF for remaining uncertainties:
1
Justification:
A factor of 1 is appropriate since the animal exposure was via ingestion per REACH guidance 8.4.2.
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:
DNEL (Derived No Effect Level)
Value:
38 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
other: EC3
AF for dose response relationship:
3
Justification:
A factor of 3 is appropriate as an EC3 value can be considered as a LOAEL for induction of skin sensitization per REACH R.8 Appendix R.8-10.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since local effects are independent of the basal metabolic rate, and the adjusted start point was via µg/cm2 (dermal). Thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
10
Justification:
A default factor of 10 is appropriate per REACH guidance 8.4.3 and Appendix R.8-10.
AF for intraspecies differences:
10
Justification:
This is a default assessment factor for the general population per REACH Guidance R.8.4.3.1
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
AF for remaining uncertainties:
1
Justification:
A factor of 1 is appropriate since the animal exposure was via the dermal route per REACH guidance 8.4.2.

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

Potential general population exposure would likely occur via the dermal route.

Based on the rat acute oral and dermal LD50 values of >5000 mg/kg and the 4-hour LC50 in rats of >0.89 mg/L (the maximum practically attainable atmospheric aerosol concentration), this substance is not classified for acute toxicity via the oral, dermal, or inhalation routes under REACH regulations and guidance. 

Male and female rats were exposed to the test substance daily via gavage in an OECD 422 study (oral toxicity with one generation reproduction screening study) at doses of 100, 300, and 1000 mg/kg. No evidence of systemic toxicity was observed at the highest dose tested, therefore the NOAEL was 1000 mg/kg. 

Although the weight of evidence suggests that this test substance is not a skin sensitizer, and the substance is not classified as a skin sensitizer, effects were produced in an acute exposure LLNA study; therefore a short-term DNEL for local effects by the dermal route was derived.

In a local lymph node assay, this substance was found to be positive for dermal sensitization with an EC3 value of 45% (11250 µg/cm2). As per REACH R.8 Appendix R. 8-10 Skin sensitization, an EC3 value can be considered as a LOAEL for induction (expressed in µg/cm2) and can be used for development of a short-term DNEL for local effects.

 

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