Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.09 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
1 207
Explanation for the modification of the dose descriptor starting point:
The inhalation NOAEC of 700 mg/m3 from the read across of Methyl salicylate is used and adjusted for molecular weight differences for homosalate to be 1207 mg/m³ .
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEC
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not required for airborne 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:
17.2 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:
860 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to the statement of toxicokinetic assessment, the absorption rate from dermal route is assumed to be <10% and the absorption rate of oral route is considered to be 100%. Therefore, the oral NOAEL of 86 mg/kg bw/d derived from the read across substance Methyl salicylate is converted to a NOAEL for the dermal route by multiplying with 100/10.
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
NOAEL derived from 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
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 the results of toxicokinetic assessment, the inhalation route is not considered further as exposure scenarios for test article do not indicate inhalative exposure to be the likely route of exposure to workers in production. However, an inhalative DNEL was derived based on the NOAEC (700 mg/m³), derived from a subacute read-across study on methyl salicylate, in which no toxic signs and no macroscopic or microscopic effects were seen following exposure to a saturated atmosphere within 28 days (7 hours exposure on 5 days/week). This NOAEC was adjusted to 1207 mg/m³ taking into account molecular weight differences from methyl salicylate to homosalate.

The absorption rate from dermal route is assumed to be less than 10% and the absorption rate of oral route is considered to be 100%. Therefore, the oral NOAEL of 50 mg/kg bw/d for general toxicity of methyl salicylate derived in a 2-year carcinogenicity study is converted to an equimolar value of 86 mg/kg bw/d of homosalate and route to route extrapolated to a dermal NOAEL of 860 mg/kg/day by multiplying by a factor of 100/10. As basis for DNEL derivation the result from a chronic study with rats on methyl salicylate was used. In this study, the test item was administered at dosages of 0.1, 0.5, 1 and 2% in diet (equivalent to 50, 250, 500 and 1000 mg/kg bw/d), and controls received diet only. Based on the results of this study, where no test article-related effects were observed at 50 mg/kg bw/d the NOAEL (No Observed Adverse Effect Level) for general toxicity in rats was considered to be 50 mg/kg bw/day (equivalent to 86 mg/kg bw/d homosalate). Hence this study is chosen as basis for dermal DNEL derivation, applying the NOAEL value (86 mg/kg bw/d adjusted to homosalate) in this study. Based on the above description, the basis for the DNEL therefore is this oral NOAEL (86 mg/kg bw/day), and NOAELcorr for the dermal route is 860 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.04 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
1 207 mg/m³
Explanation for the modification of the dose descriptor starting point:
The inhalation NOAEC of 700 mg/m3 from the read across of methyl salicylate is used and adjusted for molecular weight differences for homosalate to be 1207 mg/m³
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEC
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not required for airborne 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:
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:
8.6 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:
860 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to the statement of toxicokinetic assessment, the absorption rate from dermal route is assumed to be <10% and the absorption rate of oral route is considered to be 100%. Therefore, the oral NOAEL of 86 mg/kg bw/d derived from the read across substance Methyl salicylate is converted to a NOAEL for the dermal route by multiplying with 100/10.
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
NOAEL derived from 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:
0.86 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:
86 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to route
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
NOAEL derived from 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

According to the results of toxicokinetic assessment, the inhalation route is not considered further as exposure scenarios for test article do not indicate inhalative exposure to be the likely route of exposure to workers in production. However, an inhalative DNEL was derived based on the NOAEC (700 mg/m³), derived from a subacute read-across study on methyl salicylate, in which no toxic signs and no macroscopic or microscopic effects were seen following exposure to a saturated atmosphere within 28 days (7 hours exposure on 5 days/week). This NOAEC was adjusted to 1207 mg/m³taking into account molecular weight differences from ethyl salicylate to homosalate.

The absorption rate from dermal route is assumed to be less than 10% and the absorption rate of oral route is considered to be 100%. Therefore, the oral NOAEL of 50 mg/kg bw/d for general toxicity of methyl salicylate derived in a 2-year carcinogenicity study is converted to an equimolar value of 86 mg/kg bw/d of homosalate and route to route extrapolated to a dermal NOAEL of 860 mg/kg/day by multiplying by a factor of 100/10. As basis for DNEL derivation the result from a chronic study with rats on methyl salicylate was used. In this study, the test item was administered at dosages of 0.1, 0.5, 1 and 2% in diet (equivalent to 50, 250, 500 and 1000 mg/kg bw/d), and controls received diet only. Based on the results of this study, where no test article-related effects were observed at 50 mg/kg bw/d the NOAEL (No Observed Adverse Effect Level) for general toxicity in rats was considered to be 50 mg/kg bw/day (equivalent to 86 mg/kg bw/d homosalate). Hence this study is chosen as basis for dermal DNEL derivation, applying the NOAEL value (86 mg/kg bw/d adjusted to homosalate) in this study. Based on the above description, the basis for the DNEL therefore is this oral NOAEL (86 mg/kg bw/day), and NOAELcorr for the dermal route is 860 mg/kg bw/day.

To derive the DNEL for oral route the same study was used but no correction for route to route was applied and the adjusted NOAEL of 86 mg/kg bw/d was used directly for DNEL oral derivation, applying the assessment factors as described.