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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
126.6 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
3 165.75 mg/m³
Explanation for the modification of the dose descriptor starting point:

Experimental rat inhalatory NOAEC was converted into human inhalatory NOAEC considering: the duration of animals and workers exposure ratio (6h/8h) and the "8h human standard Respiratory volume" / "8h worker Respiratory volume" ratio (6.7 m3/10 m3).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90 days) to chronic (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
1
Justification:
Allomatric scaling is not applicable when setting an inhalation DNEL based on an inhalation animal study (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for other interspecies differences:
2.5
Justification:
Default factor mentionned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
5
Justification:
As mentionned in ECHA Guidance R8 v2, 2010: "For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 413 and GLP (Klimisch code 1)
AF for remaining uncertainties:
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.9 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
1 787 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Experimental rat inhalatory NOAEC was converted into human dermal NOAEL considering: the "8h exposure rat standard Respiratory Volume" (0.38 m3/kg); the "rat inhalatory absorption"/"human dermal absorption" ratio (50/100); the "8h worker Respiratory Volume"/"8h human standard Respiratory volume" ratio (10 m3/6.7 m3).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90 days) to chronic (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8 v2, december 2010.
AF for other interspecies differences:
2.5
Justification:
Default factor mentionned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
5
Justification:
As mentionned in ECHA Guidance R8 v2, 2010: "For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 413 and GLP (Klimisch code 1)
AF for remaining uncertainties:
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:
no hazard identified

Additional information - workers

According to CLP Regulation (EC 1272/2008), methylal has no hazardous effect regarding to acute toxicity. Therefore, no acute DNELs (systemic or local effects) were derived. The effect due to the high volatility of methylal was covered by the long-term DNELs.

No local effect was observed after repeated dose toxicity in the subchronic studies. Therefore no long-term local DNEL was derived.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
31.5 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
1 575 mg/m³
Explanation for the modification of the dose descriptor starting point:

Experimental rat inhalatory NOAEC was converted into human inhalatory NOAEC considering: the duration of animals and workers exposure (6h/8h) ratio.

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90 days) to chronic (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
1
Justification:
Allomatric scaling is not applicable when setting an inhalation DNEL based on an inhalation animal study (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for other interspecies differences:
2.5
Justification:
Default factor mentionned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
10
Justification:
As mentionned in ECHA Guidance R8 v2, 2010: "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 413 and GLP (Klimisch code 1)
AF for remaining uncertainties:
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.1 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
3 622.5
Explanation for the modification of the dose descriptor starting point:

Experimental rat inhalatory NOAEC was converted into human dermal NOAEL considering: the "24h exposure rat standard Respiratory Volume" (1.15 m3/kg); the "rat inhalatory absorption"/"human dermal absorption" ratio (50/100).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90 days) to chronic (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8 v2, december 2010.
AF for other interspecies differences:
2.5
Justification:
Default factor mentionned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
10
Justification:
As mentionned in ECHA Guidance R8 v2, 2010: "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 413 and GLP (Klimisch code 1)
AF for remaining uncertainties:
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.1 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
3 622.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Experimental rat inhalatory NOAEC was converted into human oral NOAEL considering: the "24h exposure rat standard Respiratory Volume" (1.15 m3/kg); the "rat inhalatory absorption"/"human oral absorption" ratio (50/100).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90 days) to chronic (as mentionned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8 v2, december 2010.
AF for other interspecies differences:
2.5
Justification:
Default factor mentionned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
10
Justification:
As mentionned in ECHA Guidance R8 v2, 2010: "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 413 and GLP (Klimisch code 1)
AF for remaining uncertainties:
1
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

According to CLP Regulation (EC 1272/2008), methylal has no hazardous effect regarding to acute toxicity. Therefore, no acute DNELs (systemic or local effects) were derived. The effect due to the high volatility of methylal was covered by the long-term DNELs.

No local effect was observed after repeated dose toxicity in the subchronic studies.Therefore no long-term local DNEL was derived.

 

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