Registration Dossier
Registration Dossier
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EC number: 200-467-2 | CAS number: 60-29-7
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 308 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: reference to European Communities Indicative Occupational Exposure Levels (IOEL)
- Overall assessment factor (AF):
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 616 mg/m³
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: reference to European Communities Indicative Occupational Exposure Levels (IOEL)
- Overall assessment factor (AF):
- 1
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:
- 44 mg/kg bw/day
- 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):
- 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:
- low hazard (no threshold derived)
Additional information - workers
Worker: Production of diethyl ether (DEE) is in excess of 10 t/y. According to the REACh "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishment of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on long-term exposure is normally sufficient to ensure that adverse effects do not occur. Thus, as long term DNELs, derived from an European Communities Indicative Occupational Exposure Levels (IOEL), and this substance is not classified for acute systemic toxicity via the dermal route, a separate acute dermal DNEL was not derived.
It should be noted that an IOEL short term exposure limit (STEL) of 200 ppm (616 mg/m³) was established on the basis of a human study where nasal irritation was observed starting at 200 ppm diethyl ether for 3 to 5 minutes, and this was objectionable at 300 ppm (Nelson et al, 1943, cited in Scientific Expert Group, 1991). This IOEL was used to establish a DNEL for acute systemic inhalational effects.
The available data indicate that DEE is an eye irritant but is not a skin irritant. No dose-response data are available, and as a result, a qualitative risk assessment must be performed.
Long-term DNELS
The DNEL was derived from the European Community IOEL, which was based on a human study (Nelson, 1943). In this study, most subjects tested felt that a concentration of 100 ppm (308 mg/m³) would be acceptable over an 8 hour exposure period. In this study, the first indication of nasal irritation occurred at 200 ppm, and this was objectionable at 300 ppm.
Reference: Recommendation from Scientific Expert Group on Occupational Exposure Limits for Diethyl ether 1991. (SEG/SUM/15B)
Starting dose for DNEL calculation:
308 mg/m3 (based on Occupational Exposure of 8 hours/day, 5 days/week)
Modified dose for DNEL Calculation:
Worker - Inhalation: 308 mg/m³ (no adjustment required)
Worker - Dermal = 308 mg/m³ x 10 m³ / 70 kg = 44 mg/kg
Assessment factors: No adjustments required for interspecies, exposure duration, dose response or quality of whole database as DNEL is based on an occupational limit for workers.
Absorption data: Based on the physicochemical properties of DEE alone [i.e., low molecular weight (74.12 g/mol), low Kow value (1.19), and high water solubility (61.9 g/L)], the absorption of DEE from various routes of exposure is expected to be 100%.
Final DNELs:
Worker - Inhalation: 308 mg/m³
Worker - Dermal: 44 mg/kg
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 54.5 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: reference to European Communities Indicative Occupational Exposure Levels (IOEL)
- Overall assessment factor (AF):
- 2
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
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:
- 15.6 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: reference to European Communities Indicative Occupational Exposure Levels (IOEL)
- Overall assessment factor (AF):
- 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
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 15.6 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: reference to European Communities Indicative Occupational Exposure Levels (IOEL)
- Overall assessment factor (AF):
- 2
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
Acute DNELS: General population: similar to above for worker, assessment of acute systemic effects should default to the long term systemic DNELs. A qualitative assessment of the potential irritant effect of DEE is required.
Long-term DNELs:
The long term DNEL for the general population was derived from the worker occupational exposure limit. Starting dose for DNEL calculation: 308 mg/m³ based on occupational exposure of 8 hours/day, 5 days/week. Amortized below for continuous exposure. Modified dose for DNEL calculation: General population - inhalation: (Amortized for continuous exposure) = 308 mg/m³ x 10/6.7 x 8/24 x 5/7 = 109 mg/m³ General population - oral: 109 mg/m³ x 20 m³ / 70 kg = 31.1 mg/kg (Assumed absorption of 100% in the absence of quantifiable data) General population - dermal: 109 mg/m³ x 20 m³ / 70 kg = 31.1 mg/kg/day (Assumed absorption of 100% in the absence of quantifiable data) Assessment factors: No adjustments required for interspecies, exposure duration, dose response, or quality of whole database as DNEL is based on an occupational limit for workers. REACh guidance recommends an AF of 10 for the general population and 5 for the workers. As the DNELs are based on an occupational exposure limit, an AF of 2 is applied to account for the differences between general population and the workers (10/5 = 2). Final DNELs: General population - dermal: 31.1 mg/kg / 2 = 15.6 mg/kg/day General population - inhalation: 109 mg/m³ / 2 = 54.5 mg/m³ General population - oral: 31.2 mg/kg / 2 = 15.6 mg/kg/day
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