Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 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):
75
Modified dose descriptor starting point:
NOAEC
DNEL value:
6 mg/m³
Explanation for the modification of the dose descriptor starting point:

(12 x 6.5/10 x 6h/8h)

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
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:
5.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
180
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
2.4
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
2.4
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5

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

The substance is not acutely toxic by any route of exposure, with oral and dermal LD50 values greater than 2000 mg/kg and acute inhalation LC50 greater than 250 mg/m3 (the highest attainable concentration). In addition, the substance is not irritating to the rabbit skin and eye, and does not possess skin sensitisation potential. On this basis no acute DNELs, either for systemic or local effects would be required however, as the substance has a European harmonised classification for acute dermal toxicity (although this is considered to be an error), an acute dermal DNEL for systemic effects has been calculated, using the NOEL of 1000 mg/kg/day obtained in a 28-day dermal toxicity study in rabbits as the starting point.

Repeated-dose studies are available for each route of exposure, and the NOELs for the appropriate route of exposure have been used for calculating long-term dermal and inhalation DNELs for systemic effects.

The substance is not genotoxic, not carcinogenic, and does not pose any risk for reproductive and developmental toxicity as the NOELs obtained in reproductive/developmental studies were always higher than those obtained in repeated dose oral toxicity studies.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 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):
150
Modified dose descriptor starting point:
NOAEC
DNEL value:
3 mg/m³
Explanation for the modification of the dose descriptor starting point:

(12 x 6h/24h)

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
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:
DNEL (Derived No Effect Level)
Value:
2.8 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
360
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
2.4
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
2.4
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5

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:
0.03 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):
35
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
1.4
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
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 addition to the endpoints used for calculating the DNELs for workers, the lowest NOAEL of 1 mg/kg/day obtained in dogs in a chronic 1 year toxicity study (consistently obtained in this species, the most sensitive, notwithstanding the prolongation of exposure from 28-days to 1 year) has been used for calculating the long-term oral systemic DNEL for the general population.