Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 894 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
Value:
23 671 mg/m³
Explanation for the modification of the dose descriptor starting point:
In a 2-year chronic/carcinogenicity study, 100 rats/grp/sex were exposed 6 h/d, 5 d/w to concentrations of DME of 0, 0.2, 1.0, or 2.5%. The NOAEC was established to be 2.5% = 47106 mg/m3. NOAEC workers = 6/8 * 6.7/10 * NOAEC rat.
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:
NOAEC is based on a chronic (2-year) inhalation study.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default for workers
AF for the quality of the whole database:
1
Justification:
Available data are derived from studies of appropriate quality and validity, showing consistent results.
AF for remaining uncertainties:
1
Justification:
A high quality, robust toxicity database exists for this substance.
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:
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

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 4-hr inhalation LC50 is 164000 ppm (309018 mg/m3). The LOAEL for systemic toxicity effects after a 2-hour inhalation exposure is 84000 ppm (158277 mg/m3) air, at which levelacute toxicity was observed in the form of ataxia, anaesthesia in 2 hours, short jerky respirations and lung noise (post exposure). Various repeated dose inhalation studies, including 90-day exposures were conducted for this substance. In rats, no substance related adverse effects were observed at the highest concentration tested (20000 ppm, 37685 mg/m3). In hamsters, clinical chemistry changes were not consistently dose related or statistically significant, therefore, the rat was considered for use in assessment activities. Since a high quality, chronic inhalation exposure study was available in rats, it was the most appropriate study for further health assessments.

 

Male and female rats were exposed to 0, 0.2, 1 or 2.5% v/v via inhalation for 24 months. Body weight gain (male only) was occasionally higher than controls in the early phases of the study, but this finding was not consistent throughout the study. Further the observation in increased body weight was not seen in any other of the subchronic or repeated inhalation studies involving the test substance. While there was a statistically significant decrease in survivability (males only) at the termination of the 2-yr study, no impact on survivability is observed throughout the chronic toxicity portion of the study (12 months). There were no pathological, clinical or clinical chemistry effects observed that would support a conclusion that there was a substance-related reduction in survival. The study authors did not consider the possibility that the statistical difference in survivability at the 2-yr point is due to the high survival rate of the controls in this study, and that comparison with historical control values may have led to the dismissal of the effects. Based on careful consideration of the chronic portion of this study and the supporting information of several subchronic studies involving multiple species, the repeated inhalation NOAEL is determined to be 2.5% (47106 mg/m3).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
471 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
Value:
11 777 mg/m³
Explanation for the modification of the dose descriptor starting point:
In a 2-year chronic/carcinogenicity study, 100 rats/grp/sex were exposed 6 h/d, 5 d/w to concentrations of DME of 0, 0.2, 1.0, or 2.5%. The NOAEC was established to be 2.5% = 47106 mg/m3. NOAEC general public = 6/24 * NOAEC rat.
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:
NOAEC is based on a chronic (2-year) inhalation study.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default for general public
AF for the quality of the whole database:
1
Justification:
Available data are derived from studies of appropriate quality and validity, showing consistent results.
AF for remaining uncertainties:
1
Justification:
A high quality, robust toxicity database exists for this substance.
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:
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

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 4-hr inhalation LC50 is 164000 ppm (309018 mg/m3). The LOAEL for systemic toxicity effects after a 2-hour inhalation exposure is 84000 ppm (158277 mg/m3) air, at which levelacute toxicity was observed in the form of ataxia, anaesthesia in 2 hours, short jerky respirations and lung noise (post exposure). Various repeated dose inhalation studies, including 90-day exposures were conducted for this substance. In rats, no substance related adverse effects were observed at the highest concentration tested (20000 ppm, 37685 mg/m3). In hamsters, clinical chemistry changes were not consistently dose related or statistically significant, therefore, the rat was considered for use in assessment activities. Since a high quality, chronic inhalation exposure study was available in rats, it was the most appropriate study for further health assessments.

 

Male and female rats were exposed to 0, 0.2, 1 or 2.5% v/v via inhalation for 24 months. Body weight gain (male only) was occasionally higher than controls in the early phases of the study, but this finding was not consistent throughout the study. Further the observation in increased body weight was not seen in any other of the subchronic or repeated inhalation studies involving the test substance. While there was a statistically significant decrease in survivability (males only) at the termination of the 2-yr study, no impact on survivability is observed throughout the chronic toxicity portion of the study (12 months). There were no pathological, clinical or clinical chemistry effects observed that would support a conclusion that there was a substance-related reduction in survival. The study authors did not consider the possibility that the statistical difference in survivability at the 2-yr point is due to the high survival rate of the controls in this study, and that comparison with historical control values may have led to the dismissal of the effects. Based on careful consideration of the chronic portion of this study and the supporting information of several subchronic studies involving multiple species, the repeated inhalation NOAEL is determined to be 2.5% (47106 mg/m3).