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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
39.3 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):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
491 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 NOAEL. 8 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation. Corrected inhalatory NOAEC = 557 mg/kg bw/day*(1/0.38 m3/kg/day)*(50%/100%)*(6.7 m3 (8h)/10 m3 (8h)) = 491 mg/m3
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
chronic study
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
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:
11 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):
50
Modified dose descriptor starting point:
NOAEL
Value:
557 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:
1
Justification:
chronic study
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
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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 is derived from the chronic oral toxicity study, where NOAEL is 557 mg/kg bw/day. Route-to-route (oral-inhalation) extrapolation was performed. The calculated DNEL is 39.3 mg/m3, applying the assessment factor of 12.5. Enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol in equimolar amounts. The proposed DNEL for methyl benzoate of 39.3 mg/m3 is equivalent to a methanol dose of 9.2 mg/m3. According to the ECHA dissemination page, the DNEL for effects of long-term inhalation exposure to methanol is 260 mg/m3. Hence, the inhalation dose of methanol of 9.2 mg/m3 is clearly below this inhalation DNEL. It can be concluded that methanol is likely to have low contribution to the repeated dose inhalation toxicity of methyl benzoate. A detailed assessment of methanol exposure therefore is not required.

The long-term dermal DNEL for systemic effects is derived from the chronic oral toxicity study. For the route-to-route extrapolation it was assumed that oral and dermal absorption in the rat are equal to human oral and dermal absorption. The calculated DNEL is 11 mg/kg bw/day, applying the assessment factor of 50. Enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol in equimolar amounts. The proposed DNEL for methyl benzoate of 11 mg/kg bw/day is equivalent to a methanol dose of 2.6 mg/kg bw/day. According to the ECHA dissemination page, the DNEL for effects of long-term dermal exposure to methanol is 40 mg/kg bw/day. Hence, the dermal dose of methanol of 2.6 mg/kg bw/day is clearly below this dermal DNEL. It can be concluded that methanol is likely to have low contribution to the repeated dose dermal toxicity of methyl benzoate. A detailed assessment of methanol exposure therefore is not required.

The long-term inhalation and dermal DNELs for local effects were not derived, since no local irritation potential was identified in skin irritation studies and only slight, transient effects on conjunctivae were observed.

The acute/short term inhalation DNEL for systemic effects was not required, since the substance is unlikely to exert significant acute toxicity via the inhalation route.

The acute/short term exposure dermal DNEL for systemic effects was not derived, since no hazard was identified for Methyl benzoate for dermal toxicity. It is anticipated that incidences of potential acute dermal exposure to the substance are covered with the DNEL for dermal long-term exposure of workers, i. e. 11 mg/kg bw/day. Enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol in equimolar amounts. The proposed DNEL for methyl benzoate of 11 mg/kg bw/day is equivalent to a methanol dose of 2.6 mg/kg bw/day. According to the ECHA dissemination page, the DNEL for effects of short-term dermal exposure to methanol is 40 mg/kg bw/day. Hence, the dermal dose of methanol of 2.6 mg/kg bw/day is clearly below this dermal DNEL. It can be concluded that methanol is likely to have low contribution to the acute dermal toxicity of methyl benzoate. A detailed assessment of methanol exposure therefore is not required.

The acute/short term inhalation and dermal DNELs for local effects were not derived, since no local irritation potential was identified in skin irritation studies and only slight, transient effects on conjunctivae were observed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.68 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:
NOAEC
Value:
242 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 = 557 mg/kg bw/day*(1/1.15 m3/kg/day)*(50%/100%) = 242 mg/m3
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentration
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
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:
5.57 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:
557 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:
1
Justification:
chronic study
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
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:
5.57 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:
557 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route-to-route extrapolation performed
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
chronic study
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
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 is derived from the chronic oral toxicity study with a NOAEL of 557 mg/kg bw/day. Route-to-route (oral-inhalation) extrapolation was performed. The calculated DNEL is 9.68 mg/m3, applying the assessment factor of 25. Enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol in equimolar amounts. The proposed DNEL for methyl benzoate of 9.68 mg/m3 is equivalent to a methanol dose of 2.2 mg/m3. According to the ECHA dissemination page, the DNEL for effects of long-term inhalation exposure to methanol is 50 mg/m3. Hence, the inhalation dose of methanol of 2.2 mg/m3 is clearly below this inhalation DNEL. It can be concluded that methanol is likely to have low contribution to the repeated dose inhalation toxicity of methyl benzoate. A detailed assessment of methanol exposure therefore is not required.

The long-term dermal DNEL for systemic effects is derived also from the chronic oral toxicity study. For the route-to-route (oral-dermal) extrapolation it was assumed that oral and dermal absorption in the rat are equal to human oral and dermal absorption. The calculated DNEL is 5.57 mg/kg bw/day, applying the assessment factor of 100. Enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol in equimolar amounts. The proposed DNEL for methyl benzoate of 5.57 mg/kg bw/day is equivalent to a methanol dose of 1.3 mg/kg bw/day. According to the ECHA dissemination page, the DNEL for effects of long-term dermal exposure to methanol is 8 mg/kg bw/day. Hence, the dermal dose of methanol of 1.3 mg/kg bw/day is clearly below this dermal DNEL. It can be concluded that methanol is likely to have low contribution to the repeated dose dermal toxicity of methyl benzoate. A detailed assessment of methanol exposure therefore is not required.

The long-term oral DNEL for systemic effects is derived from the chronic oral toxicity study. No route-to-route extrapolation was performed. The calculated DNEL is 5.57 mg/kg bw/day, applying assessment factor of 100. Enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol in equimolar amounts. The proposed DNEL for methyl benzoate of 5.57 mg/kg bw/day is equivalent to a methanol dose of 1.3 mg/kg bw/day. According to the ECHA dissemination page, the DNEL for effects of long-term oral exposure to methanol is 8 mg/kg bw/day. Hence, the oral dose of methanol of 1.3 mg/kg bw/day is clearly below this oral DNEL. It can be concluded that methanol is likely to have low contribution to the repeated dose oral toxicity of methyl benzoate. A detailed assessment of methanol exposure therefore is not required.

The long-term inhalation and dermal DNELs for local effects were not derived, since no local irritation potential was identified in skin irritation studies and only slight, transient effects on conjunctivae were observed. The compound is not classified for skin and eye irritation, therefore, no hazard was identified.

The acute/short term inhalation DNEL for systemic effects was not required, since the substance is unlikely to exert significant acute toxicity via the inhalation route. In addition, fragranced end-products meant for use by the general public contain low amounts of methyl benzoate, generally < 1%.

The acute/short term dermal DNEL for systemic effects was not derived, since methyl benzoate shows no acute dermal toxicity. It is anticipated that incidences of potential acute dermal exposure to the substance are covered with the DNEL for dermal long-term exposure of general population, i. e. 5.57 mg/kg bw/day. In addition, fragranced end-products meant for use by the general public contain low amounts of methyl benzoate, generally < 1%. Enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol in equimolar amounts. The proposed DNEL for methyl benzoate of 5.57 mg/kg bw/day is equivalent to a methanol dose of 1.3 mg/kg bw/day. According to the ECHA dissemination page, the DNEL for effects of short-term dermal exposure to methanol is 8 mg/kg bw/day. Hence, the dermal dose of methanol of 1.3 mg/kg bw/day is clearly below this dermal DNEL. It can be concluded that methanol is likely to have low contribution to the acute dermal toxicity of methyl benzoate. A detailed assessment of methanol exposure therefore is not required.

The acute/short term oral DNEL for system effects was not derived, since methyl benzoate exhibits only low acute oral toxicity. It is anticipated that incidences of potential acute oral exposure to the substance are covered with the DNEL for oral long-term exposure of the general population, i. e. 5.57 mg/kg bw/day. In addition, fragranced end-products meant for use by the general public contain low amounts of methyl benzoate, generally < 1%. Enzyme-driven hydrolysis of methyl benzoate in organisms releases methanol in equimolar amounts. The proposed DNEL for methyl benzoate of 5.57 mg/kg bw/day is equivalent to a methanol dose of 1.3 mg/kg bw/day. According to the ECHA dissemination page, the DNEL for effects of short-term oral exposure to methanol is 8 mg/kg bw/day. Hence, the oral dose of methanol of 1.3 mg/kg bw/day is clearly below this oral DNEL. It can be concluded that methanol is likely to have low contribution to the acute oral toxicity of methyl benzoate. A detailed assessment of methanol exposure therefore is not required.

The acute/short term exposure inhalation and dermal DNELs for local effects was not derived, since no local irritation potential could be identified in skin and eye irritation studies and therefore, no hazard was identified.