Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.34 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):
50
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
617.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 500 mg/kg bw/d taken from the combined repeated oral dose toxicity study with the reproduction/developmental toxicity screening in rats (oral administration).

Calculation of the modified dose descriptor:

NOAECcorr = NOAELoral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h))*

(7 days exposure/ 5 days exposure) = 500 mg/kg bw/day*(1/0.38 m³/kg bw/day)*(0.5/1)*0.67*1.4 = 617.1 mg/m³.

In the absence of information on oral absorption the assessment factor of 2, default value for oral-to-inhalation extrapolation is considered.

AF for dose response relationship:
1
Justification:
No assessment factor required because the dose descriptor starting point is based on a NOAEL
AF for differences in duration of exposure:
4
Justification:
As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
AF for interspecies differences (allometric scaling):
1
Justification:
Not used for inhalation results
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties identified
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:
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:
3.5 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):
200
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The ratio of the oral to the dermal absorption is considered as 1:1.
Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal)*(7 days exposure/ 5 days exposure) = 500 mg/kg bw/day *(1/1)*1.4= 700 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
4
Justification:
As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH standard AF for rat to human extrapolation.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.17 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):
100
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
217.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 500 mg/kg bw/d is taken from the combined repeated oral dose toxicity study with the reproduction/developmental toxicity screening in rats (oral administration).

Calculation of the modified dose descriptor:

NOAECcorr = NOAELoral*(1/1.15 m³/kg bw/day (24h)) *(ABSoral-rat/ABSinh-human) = 500 mg/kg bw/day*(1/1.15 m³/kg bw/day)*(0.5/1) = 217.4 mg/m³.

In the absence of information on oral absorption the assessment factor of 2, default value for oral-to-inhalation extrapolation is considered.

AF for dose response relationship:
1
Justification:
No assessment factor required.
AF for differences in duration of exposure:
4
Justification:
As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
AF for interspecies differences (allometric scaling):
1
Justification:
Not used for oral results
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties 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:
DNEL (Derived No Effect Level)
Value:
1.25 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):
400
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The ratio of the oral to the dermal absorption is considered as 1:1.

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) = 500 mg/kg bw/day *(1/1) = 500 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
No assessment factor required
AF for differences in duration of exposure:
4
Justification:
As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was the rat.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties 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:
DNEL (Derived No Effect Level)
Value:
1.25 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):
400
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification ot the dose descriptor required.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
4
Justification:
As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was the rat.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties 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