Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 713 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
DNEL value:
33 911.213 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEC was 67485 mg/m3 in a chronic toxicity/carcinogenicity inhalation study in male and female 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 robust database supports the confidence in the dose descriptor.
AF for differences in duration of exposure:
1
Justification:
No exposure time extrapolation is appropriate since the ciritical study was from a chronic inhalation study. Value adopted 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).
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 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:
low hazard (no threshold derived)
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

This is a volatile substance and potential worker exposure would likely occur via the inhalation route. Therefore, no worker oral or dermal route DNELs were derived. No local effects were observed in acute or repeated exposure studies; therefore no DNEL for local effects was derived.

This substance is not classified as toxic under REACH regulations and guidance. The rat has a 4-hour inhalation LC50 > 437500 ppm. The NOAEC for significant systemic toxicity effects from acute inhalation was 66400 ppm (179280 mg/m3) air. Male and female rats were exposed to 0, 0.2, 1, or 2.5% v/v via inhalation for 24 months. No survival or life-shortening effects were observed at any exposure concentration. Based on external peer-review of pathology results, no adverse effects organs or tissues were observed at any exposure concentration. Based on this information, the NOAEC for significant effects was 2.5% (67485 mg/m3). No human health hazard was identified. Subsequently there is no requirement to generate a DNEL, or according part B.8, to conduct an exposure assessment. However, an inhalation DNEL was generated using data from a 2-year inhalation study conducted with the test substance, and an inhalation exposure assessment was performed for workers to support the adaptation of the data requirements for testing according to section 8.6 and 8.7 of Annex X following Annex XI, section 3.2(a).

The American Industrial Hygiene Association (AIHA) has established a Workplace Environmental Exposure Level (WEEL) of 1000 ppm (2699 mg/m3) 8-hour Time Weighted Average (TWA). The AIHA WEEL is designed to be the airborne concentration of a substance that is without adverse health effects for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
675 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
16 871.25 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEC was 67485 mg/m3 in a chronic toxicity/carcinogenicity inhalation study in male and female 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 robust database supports the confidence in the dose descriptor.
AF for differences in duration of exposure:
1
Justification:
No exposure time extrapolation is appropriate since the critical study was from a chronic inhalation study. Value adopted 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.
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 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 for route-to-route extrapolation since the animal exposure was via inhalation per REACH guidance R.8.4.2.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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

This is a volatile substance and potential general population exposure would likely occur via the inhalation route. No local effects were observed in acute or repeated exposure studies; therefore no DNEL for local effects was derived. No human health hazard was identified. Subsequently there is no requirement to generate a DNEL, or according part B.8, to conduct an exposure assessment. However, an inhalation DNEL was generated using data from a 2-year inhalation study conducted with the test substance, and an inhalation exposure assessment was performed for a series of consumer uses representing high end exposure situations to support the adaptation of the data requirements for testing according to section 8.6 and 8.7 of Annex X following Annex XI, section 3.2(a).

This substance is not classified as toxic under REACH regulations and guidance. The rat has a 4-hour inhalation LC50 >437500 ppm. The NOAEC for significant systemic toxicity effects from acute inhalation was 66400 ppm (179280 mg/m3) air. Male and female rats were exposed to 0, 0.2, 1, or 2.5% v/v via inhalation for 24 months. No survival or life-shortening effects were observed at any exposure concentration. Based on external peer-review of pathology results, no adverse effects organs or tissues were observed at any exposure concentration. Based on this information, the NOAEC for significant effects was 2.5% (67485 mg/m3).