Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.43 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
BMDL10
Value:
4.37 mg/kg bw/day
Modified dose descriptor starting point:
BMCL10
Value:
5.39 mg/m³
Explanation for the modification of the dose descriptor starting point:

BMCL10corr = BMDL10oral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h))*(7 days/5 days) = 4.37 mg/kg bw/day*(1/0.38 m³/kg bw/day)*(0.5/1)*0.67*1.4 = 5.39 mg/m³.

As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption. ABS(oral/rat) = oral absorption rate in rats, ABS(inh./human) = inhalation absorption rate in humans.

Differences in the experimental (7 days/week) and human exposure conditions (worker: 5 days/week) were considered.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a BMDL10. The lower 95% confidence level of the BMC10 replaces the NOAEL as starting point.
AF for differences in duration of exposure:
1
Justification:
The effects on parturition are at a first instance considered to be limited to exposure during pregnancy. Therefore no AF allowing for differences in the experimental exposure duration is used.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
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 high-quality studies (OECD 422 Guideline study).
AF for remaining uncertainties:
1
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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 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):
50
Dose descriptor starting point:
BMDL10
Value:
4.37 mg/kg bw/day
Modified dose descriptor starting point:
BMDL10
Value:
6.12 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

BMDL10dermal = BMDL10oral*ABS(oral)/ABS(dermal)*(7 days/5 days) = 4.37 mg/kg bw/day *(1/1)*1.4 = 6.12 mg/kg bw/day.

It is assumed that oral and dermal absorption rates are equal.

Differences in the experimental (7 days/week) and human exposure conditions (worker: 5 days/week) were considered.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a BMDL10. The lower 95% confidence level of the BMC10 replaces the NOAEL as starting point.
AF for differences in duration of exposure:
1
Justification:
The effects on parturition are at a first instance considered to be limited to exposure during pregnancy. Therefore no AF allowing for differences in the experimental exposure duration is used.
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was rat.
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 high-quality studies (OECD 422 Guideline study).
AF for remaining uncertainties:
1
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:
0.076 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
BMDL10
Value:
4.37 mg/kg bw/day
Modified dose descriptor starting point:
BMCL10
Value:
1.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

BMCL10corr = BMDL10oral*(1/1.15 m³/kg bw/day (24h)) *(ABSoral-rat/ABSinh-human) = 4.37 mg/kg bw/day*(1/1.15 m³/kg bw/day)*(0.5/1) = 1.9 mg/m³.

As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption. ABS(oral/rat) = oral absorption rate in rats, ABS(inh./human) = inhalation absorption rate in humans.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a BMDL10. The lower 95% confidence level of the BMC10 replaces the NOAEL as starting point.
AF for differences in duration of exposure:
1
Justification:
The effects on parturition are at a first instance considered to be limited to exposure during pregnancy. Therefore no AF allowing for differences in the experimental exposure duration is used.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
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 high-quality studies (OECD 422 Guideline study).
AF for remaining uncertainties:
1
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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.044 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
BMDL10
Value:
4.37 mg/kg bw/day
Modified dose descriptor starting point:
BMDL10
Value:
4.37 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

BMDL10dermal = BMDL10oral*ABS(oral)/ABS(dermal) = 4.37 mg/kg bw/day *(1/1) = 4.37 mg/kg bw/day. It is assumed that oral and dermal absorption rates are equal.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a BMDL10. The lower 95% confidence level of the BMC10 replaces the NOAEL as starting point.
AF for differences in duration of exposure:
1
Justification:
The effects on parturition are at a first instance considered to be limited to exposure during pregnancy. Therefore no AF allowing for differences in the experimental exposure duration is used.
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was 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 high-quality studies (OECD 422 Guideline study).
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The test substance is not classified for acute dermal toxicity according to Regulation (EC) No 1272/2008 (CLP).

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:
0.044 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
BMDL10
Value:
4.37 mg/kg bw/day
Modified dose descriptor starting point:
BMDL10
Value:
4.37 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

no route to route extrapolation necessary

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a BMDL10. The lower 95% confidence level of the BMC10 replaces the NOAEL as starting point.
AF for differences in duration of exposure:
1
Justification:
The effects on parturition are at a first instance considered to be limited to exposure during pregnancy. Therefore no AF allowing for differences in the experimental exposure duration is used.
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was 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 high-quality studies (OECD 422 Guideline study).
AF for remaining uncertainties:
1
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