Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.45 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:
30.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of an appropriate inhalation study, route to route extrapolation was done using the reliable chronic oral repeated dose toxicity study in rats.
AF for dose response relationship:
1
Justification:
not required, starting point is a NOAEC
AF for differences in duration of exposure:
1
Justification:
a chronic study is available
AF for interspecies differences (allometric scaling):
1
Justification:
not required, starting point is a concentration
AF for other interspecies differences:
2.5
Justification:
assessment factor for remaining uncertainties
AF for intraspecies differences:
5
Justification:
assessment factor for workers
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:
hazard unknown (no further information necessary)
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:
0.7 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:
35 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of an appropriate dermal study, route to route extrapolation was done using the reliable chronic oral repeated dose toxicity study in rats.
AF for dose response relationship:
1
Justification:
not required, starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
a chronic study is available
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
assessment factor for remaining uncertainties
AF for intraspecies differences:
5
Justification:
assessment factor for workers
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:
high hazard (no threshold derived)
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

The DNELs for long-term systemic toxicity of the substance via the inhalation and dermal route were derived by route-to-route extrapolation from the chronic oral NOEL of 35 mg/kg bw/day established in a drinking water study with rats. The substance does not exhibit acute systemic toxicity and no DNELs for systemic effects following acute exposure were derived. DNELs for local long-term effects were not derived. Since the substance is a strong skin sensitizer, workers handling the neat substance or mixtures containing higher concentrations of the substance shall apply appropriate dermal protection to avoid dermal exposure to the substance. As the substance is not corrosive or irritating to skin and eyes and as no local effects were observed in available long-term repeated dose toxicity studies, no DNELs for local effects following acute exposure were derived.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.61 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:
15.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of an appropriate inhalation study, route to route extrapolation was done using the reliable chronic oral repeated dose toxicity study in rats.
AF for dose response relationship:
1
Justification:
not required, as the starting point is a NOAEC
AF for differences in duration of exposure:
1
Justification:
a chronic study is available
AF for interspecies differences (allometric scaling):
1
Justification:
not required as starting point is a concentration
AF for other interspecies differences:
2.5
Justification:
assessment factor for remaining uncertainties
AF for intraspecies differences:
10
Justification:
assessment factor for the 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:
hazard unknown (no further information necessary)
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:
0.35 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:
35 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of an appropriate dermal study, route to route extrapolation was done using the reliable chronic oral repeated dose toxicity study in rats.
AF for dose response relationship:
1
Justification:
not required, as starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
a chronic study is available
AF for interspecies differences (allometric scaling):
4
Justification:
assessment factor for allometric scaling rat to human
AF for other interspecies differences:
2.5
Justification:
assessment factor for remaining uncertainties
AF for intraspecies differences:
10
Justification:
assessment factor for the general public
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:
high hazard (no threshold derived)
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:
0.35 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:
35 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A reliable chronic oral repeated dose toxicity with rats is available.
AF for dose response relationship:
1
Justification:
not required, as starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
a chronic study is available
AF for interspecies differences (allometric scaling):
4
Justification:
assessment factor for allometric scaling rat to human
AF for other interspecies differences:
2.5
Justification:
assessment factor for remaining uncertainties
AF for intraspecies differences:
10
Justification:
assessment factor for the general public
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

The DNELs for long-term systemic toxicity of the substance via the inhalation and dermal route were derived by route-to-route extrapolation from the chronic oral NOEL of 35 mg/kg bw/day established in a drinking water study with rats. The DNEL for long-term systemic toxicity via the oral route was directly derived from the NOEL of 35 mg/kg bw/day. The substance does not exhibit acute systemic toxicity and no DNELs for systemic effects following acute exposure were derived. DNELs for local long-term effects were not derived. Since the substance is a strong skin sensitizer, there may be a hazard. However, fragranced end-products meant for end-use by the general public generally contain low amounts of the substance, which lowers the likelihood that skin sensitisation may appear. As the substance is not corrosive or irritating to skin and eyes and as no local effects were observed in available long-term repeated dose toxicity studies, no DNELs for local effects following acute exposure were derived.