Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.94 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):
150
Modified dose descriptor starting point:
NOAEC
DNEL value:
440.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL from the repeated dose study was converted to an inhalatory NOAEC according to the following formula. NOAEC = NOAEL / resp. volume (rat) x (resp. volume (human) / resp. volume (human, light activity)) x (absorption (oral) / absorption (inhal.)) = 250mg/kg b.w. / 0.38m³/kg b.w. x 0.67 x 0.5 = 440.8mg/m³
AF for dose response relationship:
1
Justification:
NOAEL was used as starting point
AF for differences in duration of exposure:
6
Justification:
subacute to chronic - factor of 6 used despite significantly longer treatment time of 50 days to account for additional uncertainties due to read across
AF for interspecies differences (allometric scaling):
1
Justification:
Already considered during route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
5
Justification:
Default factor
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
Default factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.7 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):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
66.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not required
AF for dose response relationship:
1
Justification:
NOAEL used as starting point
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
This factor describes the differences in metabolic rate between rats and humans based on body weight and is generally applicable to renally excreted substances.
AF for other interspecies differences:
1
Justification:
The NOAEL is based on the unspecific finding of reduced body weight gain in males only. No further parameters were affected. There was no specific specific organ toxicity / receptor involvement and males were only affected part of the time, while there was no change in females. Since the relevance of this change is questionable, the NOAEL is considered to be sufficiently conservative that no additional safety factor is required. Additionally, no influence of toxicodynamic differences is expected on this parameter.
AF for intraspecies differences:
5
Justification:
Default factor
AF for the quality of the whole database:
1
Justification:
Well documented study comparable to OECD guideline
AF for remaining uncertainties:
1
Justification:
Default factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

No DNELs were derived for the general population, since all consumer are advised against due to the sensitisation potential of the unreacted substance.