Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.7 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
353 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for repeated dose effects via the inhalation route is determined on the basis of route-to-route extrapolation from the oral OECD 422 study. In this study a NOAEL of 200 mg/kg bw was derived based on effects relevant for humans. The following correction was made to the NOAEL (oral): Correction for respiratory rate (rats to human): 1/0.38 (default). Correction for respiratory rate and volume (human worker): (6.7 m3/d/10 m3/d) (default). Therefore, the corrected NOAEC for toxicity via the inhalation route is: 200*(1/0.38)*(6.7 m3/d /10 m3/d) = 353 mg/m3.

AF for dose response relationship:
1
Justification:
A clear NOAEL was established
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation route)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
66.7 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
20 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for developmental effects via the dermal route is determined on the basis of route-to-route extrapolation from the oral OECD 422 study. In this study a NOAEL of 200 mg/kg bw/day was derived based on effects relevant for humans. In practice, dermal absorption of this substance is very limited.  A further correction for the known dermal absorption of 1% has been made, with the additional factor of 100: 200 mg/kg bw/day x 100 = 20000 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
A clear NOAEL was established
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.16 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):
150
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
173.91 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for repeated dose effects via the inhalation route is determined on the basis of route-to-route extrapolation from the oral OECD 422 study. In this study a NOAEL of 200 mg/kg bw was derived based on effects relevant for humans. The following correction was made to the NOAEL (oral): Correction respiratory volume rat (24 hour) 1/1.15 m³/kg bw.  Therefore, the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 200*(1/1.15) = 173.91 mg/m³.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral rat to inhaled human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
no hazard identified
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:
0.3 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Not required, oral study available.

AF for dose response relationship:
1
Justification:
A clear NOAEL was established
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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

There are no consumer uses of HL3 therefore DNELs for the dermal route is not required for the general population. A DNEL for the oral and inhalation route is calculated for the purposes of assessment of humans exposed via the environment.