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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
73 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
Value:
915 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): 0.75.  Correction for respiratory volume (worker): 6.7m3/10m3.  Therefore, the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 1820 mg/m3*(6 h/8 h)*(6.7 m3/10 m3) = 915 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:
73 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

Repeated dose toxicity is the critical systemic endpoints for workers and consumers. In both cases however, respiratory tract irritation following repeated exposures gives the lowest DNELs, so this is the overall critical endpoint for risk characterisation. D4 is not classified as mutagenic, carcinogenic or sensitising.

The DNELs used for risk characterisation for workers are therefore:

DNEL (long-term, inhalation): 73 mg/m3

DNEL (long-term, dermal): Not calculated as dermal absorption is <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:
13 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
Value:
325 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: 1820 mg/m3*(6 h/24 h)*(5/7) = 325 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:
13 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:
3.7 mg/kg bw/day
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):
100
Modified dose descriptor starting point:
NOAEL
Value:
373.75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the oral route is determined on the basis of route-to-route extrapolation from the inhalation combined chronic toxicity and carcinogenicity study conducted using a protocol comparable to OECD test guideline 453. The following correction was made to the NOAEC (inhaled): Correction for dosing frequency: 5 days/7 days. Correction for respiratory volume rat (24 hour): 1.15 m3/kg bw.  Therefore, the corrected NOAEL for repeated dose systemic effects via the oral route is: 1820 mg/m3*(1.15 m3/kg)*5/7 = 373.75 mg/kg bw/day.

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):
4
Justification:
Default (inhalation rat to oral 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

Repeated dose toxicity is the critical systemic endpoints for workers and consumers. In both cases however, respiratory tract irritation following repeated exposures gives the lowest DNELs, so this is the overall critical endpoint for risk characterisation. D4 is not classified as mutagenic, carcinogenic or sensitising.

 

The DNELs used for risk characterisation for consumers are therefore:

DNEL (long-term, oral): 3.7 mg/kg/day

DNEL (long-term, inhalation): 13 mg/m3

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