Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
97.3 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):
12.5
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 216 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEC (inhalation): Correction for experimental exposure duration: 6 h/d to 8 h/d.  Correction for respiratory volume (worker): 6.7m3/10m3.  Therefore, the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 2420 mg/m3*(6 h/8 h)*(6.7 m3/10 m3) = 1216 mg/m3.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
Default (chronic study)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation rat to inhalation 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:
Default
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
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:
24.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
Default (chronic study)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation rat to inhalation 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:
Default
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
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:
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

In the absence of any adverse findings relating to repeated dose toxicity in relevant studies, or reproductive and developmental endpoints in a two-generation reproductive toxicity study, the critical health effect is considered to be local respiratory irritation following repeated exposures. D5 is not classified as mutagenic, carcinogenic or sensitising.

The DNELs used for risk characterisation for workers are:

DNEL (long-term, inhalation): 24.2 mg/m3

DNEL (long-term, dermal): Not calculated as dermal absorption is significantly less than 1% and no hazard has been identified in dermal studies.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.3 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
432 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEC (inhalation): Correction for experimental exposure duration: 6 h/d to 24 h/d. Correction for dosing frequency: 5 days / 7 days. Therefore, the corrected NOAEC for repeated-dose systemic effects via the inhalation route is:  2420 mg/m3 * 6 h/24 h*5 days/7 days ≥ 432 mg/m3.   

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
Default (chronic study)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation rat to inhalation 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:
Default
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
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:
4.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
Default (chronic study)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation rat to inhalation 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:
Default
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
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:
5 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):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic study)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral in rat to oral in 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:
Default
AF for remaining uncertainties:
1
Justification:
Default (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

In the absence of any findings relating to repeated dose toxicity in relevant studies, or reproductive and developmental endpoints in a two-generation reproductive toxicity study, the critical health effect for inhalation exposure is considered to be local respiratory tract irritation following repeated exposures. D5 is not classified as mutagenic, carcinogenic or sensitising.

 

The DNELs used for risk characterisation for consumers are therefore:

DNEL (long-term, inhalation): 4.3 mg/m3

DNEL (long-term, dermal): Not calculated as dermal absorption is significantly less than 1% and no hazard has been identified in dermal studies.

DNEL (long-term, oral): 5 mg/kg bw/day