Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
58.7 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):
30
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:

Guidance

AF for dose response relationship:
1
Justification:
No observed adverse effects
AF for differences in duration of exposure:
6
Justification:
Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Factored into breathing rates
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
Guidance
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
DNEL value:
800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Same route

AF for dose response relationship:
1
Justification:
No adverse effects up to maximum dose
AF for differences in duration of exposure:
6
Justification:
Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
Guidance
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
Guidance, worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Report attached to show how these figures were derived, although default figures from guidance were used.

The low dermal local results reflect possible sensitisation results as allometric scaling has been retained for inter-species difference.

The inhalation DNELs are above the normal expected exposure levels and risk management is considered adequate in the workplace.

The 28 day oral study showed minimal effects with a NOAEL considered to be 1000 mg/kg/day.

Toxicologically relevant changes were evident in the kidneys beginning at 300 mg/kg in males and at 1000 mg/kg in females, where the alpha-globulin nephropathy and tubular basophilia are not supposed to be relevant for humans. Necropsy, organ weight measurements and histopathology revealed no toxicologically relevant alterations in the remaining organs investigated.

Although the Chinese dermal test report suggests a NOEAL of 40 mg/kg/day, there is no evidence for this in the test report and minor blood parameter changes are conisdered adaptive. A NOEAL of 400 mg/kg/day is suggested by the reviewer, but it is likely that there were no adverse effects at the highest treated group of 800 mg/kg/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Report attached to show how these figures were derived, although default figures from guidance were used.

There is no exposure of the substance as such to the general public.