Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 439 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
14 389 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL was 28634 mg/m3 in a 90-day repeat inhalation study in rats. A modification (0.75) of starting point for worker exposure time as compared to animal exposure (6 hours vs. 8 hours) was applied per REACH guidance R.8.4.2. A modification (6.7 m3/10 m3) 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:
The dose descriptor is the NOAEL from a robust repeat-dose exposure study in rats that assessed a variety of endpoints. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for differences in duration of exposure:
2
Justification:
There was no systemic toxicity observed in rat and dog 90-day repeated inhalation studies conducted at 10000 ppm (28634 mg /m3) or 5000 ppm, respectively, nor in a rat developmental study conducted at 50000 ppm (143170 mg /m3). It is unlikely that increased exposure duration would produce systemic toxicity. Based on the robust repeated inhalation data, an assessment factor of 2 is appropriate 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 inhalation (mg/m3), per REACH guidance Appendix R. 8-2.
AF for other interspecies differences:
1
Justification:
No systemic toxicity was observed in repeated inhalation exposures in multiple species, even at extremely high exposure concentrations. This substance is of very low toxicity, and is not likely to exert any “unique” effect on humans. Based on the lack of systemic toxicity in multiple species, an assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
5
Justification:
No systemic toxicity was observed in repeated inhalation exposures in multiple species, even at extremely high exposure concentrations. This substance is of very low toxicity, and is not likely to exert any “unique” effect on humans, and no sensitive workplace population would be expected. While the default assessment of 5 is considered overly conservative, in the absence of other arguments, a default assessment factor of 5 is appropriate 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. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for remaining uncertainties:
1
Justification:
A factor of 1 for route-to-route extrapolation is appropriate since the animal exposure was via inhalation per REACH guidance R.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:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - workers

The substance is a gas, and is not classified as hazardous or irritating. Any workplace exposure would occur via inhalation in unprotected workers, therefore, no dermal or oral DNELs are appropriate. The substance has very low acute inhalation toxicity, and no acute systemic or local effects DNELs are appropriate. The substance also has very low systemic toxicity potential. No systemic toxicity was observed in rats or dogs exposed for 90 days to the highest substance concentrations tested, 10000 ppm (28634 mg/m3) and 5000 ppm (14317 mg/m3), respectively. In addition, no systemic toxicity was observed during a rat pre-natal developmental toxicity study conducted at 50000 ppm (143170 mg/m3). The 90-day rat repeated inhalation study is the key study for use in risk assessment, and the NOAEC of 28634 mg/m3 (10000 ppm) is the starting point for DNEL calculation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
358 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
Value:
7 159 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL was 28634 mg/m3 in a 90-day inhalation study in rats. A modification (0.25) of starting point for general population exposure time as compared to animal exposure (6 hours vs. 24 hours) was applied per REACH guidance R.8.4.2.
AF for dose response relationship:
1
Justification:
The dose descriptor is the NOAEL from a robust repeat-dose exposure study in rats that assessed a variety of endpoints. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for differences in duration of exposure:
2
Justification:
There was no systemic toxicity observed in rat and dog 90-day repeated inhalation studies conducted at 10000 ppm (28634 mg /m3) or 5000 ppm, respectively, nor in a rat developmental study conducted at 50000 ppm (143170 mg /m3). It is unlikely that increased exposure duration would produce systemic toxicity. Based on the robust repeated inhalation data, an assessment factor of 2 is appropriate 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 inhalation (mg/m3), per REACH guidance Appendix R. 8-2.
AF for other interspecies differences:
1
Justification:
No systemic toxicity was observed in repeated inhalation exposures in multiple species, even at extremely high exposure concentrations. This substance is of very low toxicity, and is not likely to exert any “unique” effect on humans. Based on the lack of systemic toxicity in multiple species, an assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
No systemic toxicity was observed in repeated inhalation exposures in multiple species, even at extremely high exposure concentrations. This substance is of very low toxicity, and is not likely to exert any “unique” effect on humans. While the default assessment of 10 is considered overly conservative, in the absence of other arguments, a default assessment factor of 10 is appropriate 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. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for remaining uncertainties:
1
Justification:
A factor of 1 for route-to-route extrapolation is appropriate since the animal exposure was via inhalation per REACH guidance R.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:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - General Population

The substance is a gas, and is not classified as hazardous or irritating. Any general population exposure would occur via inhalation; therefore, no dermal or oral DNELs are appropriate. The substance has very low acute inhalation toxicity, and no acute systemic or local effects DNELs are appropriate. The substance also has very low systemic toxicity potential. No systemic toxicity was observed in rats or dogs exposed for 90 days to the highest substance concentrations tested, 10000 ppm (28634 mg/m3) and 5000 ppm (14317 mg/m3), respectively. In addition, no systemic toxicity was observed during a rat pre-natal developmental toxicity study conducted at 50000 ppm (143170 mg/m3). The 90-day rat repeated inhalation study is the key study for use in risk assessment, and the NOAEC of 28634 mg/m3 (10000 ppm) is the starting point for DNEL calculation.