Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
27.6 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):
11
Dose descriptor starting point:
NOAEC
Value:
605 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
304.01 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEC (inhalation): Correction for experimental exposure duration (6 h/d to 8 h/d), Correction for respiratory volume (worker): 6.7 m3/10 m3. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 605*(6 h/ 8 h) *(6.7 m3/10 m3) =  304.01 mg/m3.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default
AF for interspecies differences (allometric scaling):
1
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
2.2
Justification:
Substance-specific assessment factor (see section 7.1 on Toxicokinetics, metabolism and distribution)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
3.9 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):
44
Dose descriptor starting point:
NOAEC
Value:
605 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
172.43 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEC (inhaled): Correction respiratory volume rat (8 hour) = 0.38 m³/kg bw. Correction for duration: 6 hours/8 hours. (or relevant exposure period from study/8 hour working day). Therefore, the corrected NOAEL for repeat-dose systemic effects via the dermal route is: inhaled 605*0.38*(6/8) = 172.43 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
2.2
Justification:
Substance-specific assessment factor (see section 7.1 on Toxicokinetics, metabolism and distribution)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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

For the hydrolysis product methanol, the occupational exposure limit (OEL) is 260 mg/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.9 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):
8
Dose descriptor starting point:
NOAEC
Value:
605 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
151.25 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL for infrequent inhalation exposures

Correction for exposure duration (6h/24h) was applied, but no correction for number of exposures (5d/7d) was made as infrequent exposure is expected. Therefore, 605*(6/24) = 151.25 mg/m³

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
Default for infrequent exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
3.2
Justification:
Substance-specific assessment factor (see section 7.1 on Toxicokinetics, metabolism and distribution)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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
DNEL extrapolated from long term DNEL

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.8 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):
64
Dose descriptor starting point:
NOAEC
Value:
605
Modified dose descriptor starting point:
NOAEL
Value:
496.96 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEC (inhaled): Correction respiratory volume rat (24 hour) = 1.15 m³/kg bw. Correction for dosing frequency: 5 days/7 days. Therefore, the corrected NOAEL for repeat-dose systemic effects via the oral route is: inhaled 605*1.15*(5/7) = 496.96 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
3.2
Justification:
Substance-specific assessment factor (see section 7.1 on Toxicokinetics, metabolism and distribution)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
0.3 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):
192
Dose descriptor starting point:
NOAEL
Value:
62.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
62.5 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
3.2
Justification:
Substance-specific assessment factor (see section 7.1 on Toxicokinetics, metabolism and distribution)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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

For the hydrolysis product methanol, the occupational exposure limit (OEL) is 260 mg/m3. The OEL is an 8 hours/day, 5 days/week value, so for general population inhaled exposure the corresponding value would be 260*(5/7)*(8/24) = 62 mg/m3. Therefore, the inhaled long term DNEL of methanol for general population is 62 mg/m3.