Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.1 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):
10
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
141.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

A NOAEL of 160 mg/kg/day established in the 90 days dermal repeated dose toxicity study was used to derive a DNEL long-term, systemic effects via the inhalation route (dermal route, OECD 411; Pharmakon Research International, 1990). A justification for DNEL derivation strategy is included as an attachment in this section.

After route-to-route extrapolation from dermal to inhalation, the dose descriptor starting point NOAEC is 141.1 mg/m³ = 160 mg/kg/day x 1/0.38 m³/kg/day x 0.67 x 0.5. The dermal 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 respective conditions (6.7 m³ for base level, 10 m³ for light activity). A correction factor of 0.5 is applied as bioavailability after dermal exposure is assumed to be 50% and the bioavailability after inhalation exposure is assumed to be 100%.

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:
difference in duration, subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
included in the route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
default value for effects on skin, eye and GI tract via simple destruction of membranes
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
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:
1.6 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:
160 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A long-term dermal toxicity study is available for the test substance. No route-to-route extrapolation is required.

The NOAEL (dermal route) observed in the 90d repeated dose toxicity study was used to derive a DNEL, long-term systemic effects via the dermal route. The study was performed according to OECD guideline 411 and in compliance with GLP (Pharmakon Research International, 1990). The NOAEL was considered to be 160 mg/kg bw/day.

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:
difference in duration, subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default assessment value
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
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:
no hazard identified
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:
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
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