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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
LOAEC
Value:
308.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation study is available and NOAEC was derived by route to route extrapolation from the systemic oral NOAEL. 8 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation. Corrected inhalatory NOAEC = 350 mg/kg bw/day*(1/0.38 m3/kg/day)*(50%/100%)*(6.7 m3 (8h)/10 m3 (8h)) = 308.6 mg/m3
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentrations
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
assumed that rat oral and dermal absorptions are equal to human oral and dermal absorption
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The long term inhalation DNEL for systemic effects was calculated from ca. 17-week oral (gavage) repeated dose toxicity study in rat. The NOAEC of 308.6 mg/m3 was derived by route to route extrapolation from oral NOAEL determined for systemic effects. The calculated DNEL is 12.3 mg/m3, applying the assessment factor of 25.

 

The acute/short term inhalation DNEL for systemic effects was not assessed, since no adequate quantitative NOAEL could be identified. No hazard for this endpoint was suggested based on the waiver for the acute inhalation toxicity study supported by the regulation (EC) 1907/2006 Annex XI (1.2 Weight of evidence).

 

From a skin sensitisation study it is known that DMI shows sensitising properties. The long-term inhalation and dermal DNELs for local effects were not derived since no quantitative NOAEL could be identified. Medium hazard for these endpoints was suggested based on ECHA Practical Guide 15 and skin sensitization study, where DMI is classified into category 1 (sub-category 1B).

 

The acute/short term inhalation DNEL for local effects was not assessed, since no quantitative NOAEL could be identified. Low hazard for this endpoint was suggested based on ECHA Practical Guide 15 and skin irritation study, where DMI is classified into category 2.

 

The long term dermal DNEL for systemic effects was calculated from ca. 17-week oral (gavage) repeated dose toxicity study in rat. The DNEL was derived by route to route extrapolation from oral NOAEL set for systemic effects. The calculated DNEL is 3.5 mg/kg bw/day, applying the assessment factor of 100.

 

The acute/short term dermal DNEL for systemic effects was not assessed, since no quantitative NOAEL could be identified. The substance showed relatively low acute oral toxicity (LD > 2000 mg/kg bw) suggesting that dermal toxicity will be identical or less hazardous, therefore the hazard was qualified to be low based on ECHA Practical Guide 15.

 

The acute/short term dermal DNEL for local effects was not assessed, since no quantitative NOAEL could be identified. Low hazard for this endpoint was suggested based on ECHA Practical Guide 15 and skin irritation study, where DMI is classified into category 2.

No hazard for the eyes was identified, since in a reliable eye irritation study (OECD TG 405) the test item is not irritating in rabbit eye. 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.04 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
152.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation study is available and the NOAEC was derived by route to route extrapolation from the oral NOAEL. 24 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation. Corrected inhalatory NOAEC = 350 mg/kg bw/day*(1/1.15 m3/kg/day)*(50%/100%) = 152.2 mg/m3
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentrations
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.75 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
assumed that rat oral and dermal absorptions are equal to human oral and dermal absorption
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.75 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
starting point: NOAEL from oral study
AF for dose response relationship:
1
Justification:
not required, starting point is NOEAL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The long term inhalation DNEL for systemic effects was calculated from ca. 17-week oral (gavage) repeated dose toxicity study in rat. The NOAEC of 152.2 mg/m³ was derived by route to route extrapolation from oral NOAEL determined for systemic effects. The calculated DNEL is 3.04 mg/m³, applying the assessment factor of 50.

 

The acute/short term inhalation DNEL for systemic effects was not assessed, since no adequate quantitative NOAEL could be identified. No hazard for this endpoint was suggested based on the waiver for the acute inhalation toxicity study supported by the regulation (EC) 1907/2006 Annex XI (1.2 Weight of evidence).

From a skin sensitisation study it is known that DMI shows sensitising properties. The long-term inhalation and dermal DNELs for local effects were not derived since no quantitative NOAEL could be identified. Medium hazard for these endpoints was suggested based on ECHA Practical Guide 15 and skin sensitization study, where DMI is classified into category 1 (sub-category 1B).

 

The acute/short term inhalation DNEL for local effects was not assessed, since no adequate quantitative NOAEL could be identified. Low hazard for this endpoint was suggested based on ECHA Practical Guide 15 and skin irritation study, where DMI is classified into category 2.

 

The long term dermal DNEL for systemic effects was calculated from ca. 17-week oral (gavage) repeated dose toxicity study in rat. The DNEL was derived by route to route extrapolation from oral NOAEL determined for systemic effects. The calculated DNEL is 1.75 mg/kg bw/day, applying the assessment factor of 200.

 

The acute/short term dermal DNEL for systemic effects was not assessed, since no quantitative NOAEL could be identified. The substance showed relatively low acute oral toxicity (LD > 2000 mg/kg bw) suggesting that dermal toxicity will be identical or less hazardous, therefore no hazard was qualified based on ECHA Practical Guide 15.

 

The acute/short term dermal DNEL for local effects was not assessed, since no quantitative NOAEL could be identified. Low hazard for this endpoint was suggested based on ECHA Practical Guide 15 and skin irritation study, where DMI is classified into category 2.

 

The long term oral DNEL for systemic effects was calculated from ca. 17-week oral (gavage) repeated dose toxicity study in rat. The starting point was the systemic NOAEL = 350 mg/kg bw/day. The calculated DNEL is 1.75 mg/kg bw/day DMI, applying the assessment factor of 200.

 

The acute/short term oral DNEL for systemic effects was not assessed, since no quantitative NOAEL could be identified. The substance showed relatively low acute oral toxicity (LD50 > 2000 mg/kg bw), therefore no hazard was qualified based on ECHA Practical Guide 15.

No hazard for the eyes was identified, since in a reliable eye irritation study (OECD TG 405) the test item is not irritating in rabbit eye.