Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
132 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):
5
Modified dose descriptor starting point:
NOAEC
Value:
661 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation Systemic effects - Long-term: Based on the toxicokinetic data, it can be assumed that the systemic bioavailability will be high both after oral and inhalation exposure; no correction factor for oral-to-inhalation extrapolation was applied.
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
NOAEL from chronic study
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
for workers; R8, ECHA 2008
AF for the quality of the whole database:
1
Justification:
based on validity of studies performed
AF for remaining uncertainties:
1
Justification:
(a factor 1 was used for remaining interspecies differences, because 375 mg/kg/day was the highest dose tested in the chronic study and did not cause any effects, suggesting that the NOAEL would have been higher, and the level did also not cause any effects on other species, namely in the mouse at the highest tested dose of 667 mg/kg/day in a chronic study, in the hamster at the highest tested dose of 405 mg/kg/day in a teratogenicity study, and in the rabbit at the highest tested dose of 425 mg/kg/day in a teratogenicity study, which does not indicate any relevant species differences in susceptibility
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: VCI document "Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität" see attachment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: VCI document "Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität" see attachment

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19 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):
20
Modified dose descriptor starting point:
NOAEL
Value:
375 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal Systemic effects - Long-term: Based on the toxicokinetic data, it can be assumed that the systemic bioavailability will be not higher after dermal exposure compared to oral exposure; no correction factor is applied
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
NOAEL from chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
according to R8, ECHA 2008
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
for workers; see R8, ECHA 2008
AF for the quality of the whole database:
1
Justification:
based on validity of studies performed
AF for remaining uncertainties:
1
Justification:
a factor 1 was used for remaining interspecies differences, because 375 mg/kg/day was the highest dose tested in the chronic study and did not cause any effects, suggesting that the NOAEL would have been higher, and the level did also not cause any effects on other species, namely in the mouse at the highest tested dose of 667 mg/kg/day in a chronic study, in the hamster at the highest tested dose of 405 mg/kg/day in a teratogenicity study, and in the rabbit at the highest tested dose of 425 mg/kg/day in a teratogenicity study, which does not indicate any relevant species differences in susceptibility
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The local effect long term and acute exposure assessment has taken into consideration hazards to eyes together with skin hazards, as described in attached VCI-document "Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität". In addition workers operating with chemicals, as a minimum use eye protection as default which is also communicated as a standard minimum requirement via Safety Data Sheets. Taking into consideration that the eye irritating potential is rather low, at the lower end of CLP classification criteria, leading to classification according to CLP but not according to DSD. Concentrations below 25% are not irritating. Conclusion is that L Menthol is of medium hazard.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33 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):
10
Modified dose descriptor starting point:
NOAEC
Value:
326 mg/m³
Explanation for the modification of the dose descriptor starting point:
Based on the toxicokinetic data, it can be assumed that the systemic bioavailability will be high both after oral and inhalation exposure; thus no correction factor for oral-to-inhalation extrapolation was applied.
AF for differences in duration of exposure:
1
Justification:
NOAEL from chronic study
AF for intraspecies differences:
10
Justification:
for general population; R8, ECHA 2008
AF for the quality of the whole database:
1
Justification:
based on validity of studies performed
AF for remaining uncertainties:
1
Justification:
a factor 1 was used for remaining interspecies differences, because 375 mg/kg/day was the highest dose tested in the chronic study and did not cause any effects, suggesting that the NOAEL would have been higher, and the level did also not cause any effects on other species, namely in the mouse at the highest tested dose of 667 mg/kg/day in a chronic study, in the hamster at the highest tested dose of 405 mg/kg/day in a teratogenicity study, and in the rabbit at the highest tested dose of 425 mg/kg/day in a teratogenicity study, which does not indicate any relevant species differences in susceptibility
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:
skin irritation/corrosion
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:
9.4 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
375 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Based on the toxicokinetic data, it can be assumed that the systemic bioavailability will be high both after oral and dermal exposure; no correction factor is applied.
AF for differences in duration of exposure:
1
Justification:
NOAEL from chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
R8, ECHA 2008
AF for intraspecies differences:
10
Justification:
for general population; R8, ECHA 2008
AF for the quality of the whole database:
1
Justification:
based on validity of studies performed
AF for remaining uncertainties:
1
Justification:
a factor 1 was used for remaining interspecies differences, because 375 mg/kg/day was the highest dose tested in the chronic study and did not cause any effects, suggesting that the NOAEL would have been higher, and the level did also not cause any effects on other species, namely in the mouse at the highest tested dose of 667 mg/kg/day in a chronic study, in the hamster at the highest tested dose of 405 mg/kg/day in a teratogenicity study, and in the rabbit at the highest tested dose of 425 mg/kg/day in a teratogenicity study, which does not indicate any relevant species differences in susceptibility
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.4 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
375 mg/kg bw/day
AF for differences in duration of exposure:
1
Justification:
NOAEL from chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
R8, ECHA 2008
AF for intraspecies differences:
10
Justification:
for general population; R8, ECHA 2008
AF for the quality of the whole database:
1
Justification:
based on validity of studies performed
AF for remaining uncertainties:
1
Justification:
a factor 1 was used for remaining interspecies differences, because 375 mg/kg/day was the highest dose tested in the chronic study and did not cause any effects, suggesting that the NOAEL would have been higher, and the level did also not cause any effects on other species, namely in the mouse at the highest tested dose of 667 mg/kg/day in a chronic study, in the hamster at the highest tested dose of 405 mg/kg/day in a teratogenicity study, and in the rabbit at the highest tested dose of 425 mg/kg/day in a teratogenicity study, which does not indicate any relevant species differences in susceptibility
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

L Menthol is classified as eye irritant in concentrations as of 25% and above. It should be taken into consideration that the eye irritating potential is rather low, at the lower end of CLP classification criteria, leading to classification according to CLP but not according to DSD. Concentrations below 25% are not irritating. The general population is exposed only to low concentrations of L Menthol and thus no effects have to be taken into consideration for general population.