Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.58 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
132.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

As no long-term study on inhalation is available, route-to-route extrapolation has been performed (oral to inhalation).

The NOAEL (oral route) observed in an Extended One-Generation Reproductive Toxicity Study, performed according to OECD 443 guideline (Barnett, 2020), was used to derive a DNEL long-term, systemic effects via the inhalation route. The NOAEL was established to be 150 mg/kg bw/day. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point is 132.2 mg/m³ = 150 mg/kg bw/day x 1/(0.38 m³/kg bw/day) x 6.7 m³/10 m³ x 0.5. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure for 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 is derived from the inhaled volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity).  In addition, the NOAEL needed to be divided by 2 as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%.

AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point, no additional assessment factor is required
AF for differences in duration of exposure:
1
Justification:
The study is a chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
covered by calculation for route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
5
Justification:
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
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
100
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A 90 -day repeated dose toxicity study with dermal application of the test substance was performed according to GLP requirements and equivalent to the OECD guideline 411 (Pharmakon Research International Inc., 1990; key study, Klimisch 2). The NOAEL in this study is established at 250 mg/kg bw/day. The DNEL for long-term, systemic effects for the dermal route of exposure was derived with the NOAEL (dermal) of 250 mg/kg bw/day as dose descriptor starting point.

AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point, no additional assessment factor is required.
AF for differences in duration of exposure:
2
Justification:
difference in study duration, subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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