Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26.45 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):
20
Modified dose descriptor starting point:
NOAEC
Value:
529 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 (dermal) / absorption (inhal.)) = 300mg/kg b.w. / 0.38m³/kg b.w. x 0.67 x 1 = 529mg/m³
AF for dose response relationship:
1
Justification:
NOAEL was used as starting point
AF for differences in duration of exposure:
4
Justification:
The animals were treated for up to 51 days, no gender differences were observed. A factor of 2 was chosen to extrapolate to subchronic exposure, and an additional factor of 2 for extrapolation to chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Already considered during route to route extrapolation.
AF for other interspecies differences:
1
Justification:
Besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used. In the oral repeated dose study, no specific systemic effects were observed. Already following the precautionary principle, the NOAEL was set at the mid dose, although effects observed in high dose animals are most likely only secondary to local irritation. No additional interspecies differences are expected for this effect. In addition rodents like the rat are in general more sensitive compared to human. Anatomical differences as well as air flow patterns between rodents and humans have to be taken into account. Within the ERASM project, studies in rats and mice were being examined. The results suggest that a factor of 2.5 for 'remaining‘ interspecies differences may be questionable as a default value (Escher and Mangelsdorf, 2009; Batke et al, 2011; Bitsch et al, 2006).
AF for intraspecies differences:
5
Justification:
default factor for workers
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:
3.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The same uptake fraction is assumed after oral and dermal exposure.
AF for dose response relationship:
1
Justification:
NOAEL was used as starting point
AF for differences in duration of exposure:
4
Justification:
The animals were treated for up to 51 days, no gender differences were observed. A factor of 2 was chosen to extrapolate to subchronic exposure, and an additional factor of 2 for extrapolation to chronic exposure.
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:
Within the ERASM project, studies in rats and mice were being examined to substantiate whether the factors for allometry and 'remaining‘ differences would be appropriate for these species. The results suggest that a factor of 2.5 for 'remaining‘ interspecies differences may be questionable as a default factor (Escher and Mangelsdorf, 2009; Batke et al, 2011; Bitsch et al, 2006). In the oral repeated dose study, no specific systemic effects were observed. Already following the precautionary principle, the NOAEL was set at the mid dose, although effects observed in high dose animals are most likely secondary to severe local irritation. No additional interspecies differences are expected for this effect.
AF for intraspecies differences:
5
Justification:
Default factor for workers
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:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
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

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:
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

General Population - Hazard via oral 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

As there are no consumer uses, no consumer DNELs were derived.