Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.74 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
218.48 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term repeated dose toxicity study via the inhalation route of administration is available for the test substance. Data available from an oral prenatal developmental study in rabbits (Barnett, 2020) shows a NOAEL of 75 mg/kg bw/day. This NOAEL was selected as a dose descriptor starting point. For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 75 mg/kg bw/day x 1/(0.23 m³/kg bw/d) x 6.7 m³/10 m³ x 1 = 218.48 mg/m³. The oral dose for rabbits was converted to the corresponding air concentration using a standard breathing volume for the rabbit (0.23 m3/kg for 8 hours exposure of workers). For workers, the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). No correction for bioavailability via the inhalation route is made as for both the oral and the inhalatory route, 100% absorption is assumed.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for difference in duration from a subacute to chronic toxicity would be 6. A deviating assessment factor of 2 is considered for the following reasons: the selected dose descriptor starting point NOAEL of 75 mg/kg bw/day was determined based on maternal toxicity effects in a prenatal development study in rabbits. This maternal toxicity was observed at dose levels lower than observed in other repeated dose toxicity studies. The differences in experimental exposure duration and duration of exposure of the pregnant population could be considered minor. It is generally assumed that pregnant animals are more sensitive than non-pregnant animals. Exposure to the test substance during pregnancy is to be avoided for the worker population.
AF for interspecies differences (allometric scaling):
1
Justification:
included in the route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default assessment factor for rats
AF for intraspecies differences:
5
Justification:
default assessment factor for worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
1.25 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term dermal repeated dose toxicity study is available for the test substance. Data available from an oral prenatal developmental study in rabbits shows a NOAEL of 75 mg/kg bw/day. This NOAEL was selected as dose descriptor starting point. For the route-to-route extrapolation from oral to dermal, on the assumption that dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be applied as part of the overall assessment factor.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for difference in duration from a subacute to chronic toxicity would be 6. A deviating assessment factor of 2 is considered for the following reasons: the selected dose descriptor starting point NOAEL of 75 mg/kg bw/day was determined based on maternal toxicity effects in a prenatal development study in rabbits. This maternal toxicity was observed at dose levels lower than observed in other repeated dose toxicity studies. The differences in experimental exposure duration and duration of exposure of the pregnant population could be considered minor. It is generally assumed that pregnant animals are more sensitive than non-pregnant animals. Exposure to the test substance during pregnancy is to be avoided for the worker population.
AF for interspecies differences (allometric scaling):
2.4
Justification:
default assessment factor, rabbit to human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
default assessment factor for worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

No consumer use is expected, therefore no hazard assessment for the general population is performed.