Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.53 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:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
176.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 200 mg/kg/day from an OECD422 repeat dose oral study with rats was used. (There were no systemic findings of toxicological significance in animals of either sex).

The worst case assumption is as folows for route-to-route extrapolation:

Corrected inhal N(L)OAEC = oral N(L)OAELrat * 1/0.38 * 0.5/1 * 6.7/10

Corrected inhal N(L)OAEC = oral N(L)OAELrat * 1/sRVrat * ABSoral-rat/ABSinhhuman * 6.7/10

Assuming a ABSoral-rat/ABSinh-rat of (0.5/1) 0.5 a dose descriptor of 176.3 mg/m3 was derived as the starting point.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
4
Justification:
OECD 422 with +/- 45 days exposure and 10 animals/sex/dose = AF 4
AF for interspecies differences (allometric scaling):
1
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 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:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 200 mg/kg/day from an OECD422r epeat dose oral study with rats was used. (There were no findings of systemic toxicological significance in animals of either sex).

Oral absorption rat – oral/dermal absorption human: Assume 100% absorption.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
4
Justification:
OECD 422 with +/- 45 days exposure and 10 animals/sex/dose = AF 4
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
DNEL (Derived No Effect Level)
Value:
0.87 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:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
86.96 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 200 mg/kg/day from an OECD422 repeat dose oral study with rats was used. (There were no systemic findings of toxicological significance in animals of either sex).

The worst case assumption is as folows for route-to-route extrapolation:

Corrected inhal N(L)OAEC = oral N(L)OAELrat * 1/1.15 * 0.5/1

Corrected inhal N(L)OAEC = oral N(L)OAELrat * 1/sRVrat * ABSoral-rat/ABSinhhuman

Assuming a ABSoral-rat/ABSinh-rat of (0.5/1) 0.5 a dose descriptor of 86.96 mg/m3 was derived as the starting point.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
4
Justification:
OECD 422 with +/- 45 days exposure and 10 animals/sex/dose = AF 4
AF for interspecies differences (allometric scaling):
1
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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):
400
Dose descriptor starting point:
NOAEL
Value:
200 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 200 mg/kg/day from an OECD422 repeat dose oral study with rats was used. (There were no findings of systemic toxicological significance in animals of either sex).

Oral absorption rat – oral/dermal absorption human: Assume 100% absorption.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
4
Justification:
OECD 422 with +/- 45 days exposure and 10 animals/sex/dose = AF 4
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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):
400
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 200 mg/kg/day from an OECD422 repeat dose oral study with rats was used. (There were no findings of systemic toxicological significance in animals of either sex).

Oral absorption rat – oral/dermal absorption human: Assume 100% absorption.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
4
Justification:
OECD 422 with +/- 45 days exposure and 10 animals/sex/dose = AF 4
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population