Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.03 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):
300
Dose descriptor starting point:
NOAEL
Value:
1.03 mg/m³
Value:
1.03 mg/m³
Explanation for the modification of the dose descriptor starting point:

A worker long-term inhalation DNEL was developed from the reproductive NOAEL of 350 mg/kg/day from the OECD 422 study.

The dose descriptor was corrected for an inhalation exposure with the factor of 0.38 m3/kg.

350 mg/kg /0.38 m3/kg = 921.05 mg/m3

This was further corrected for 50% oral bioavailability

921.05 mg/m3 /2 = 460.53 mg/m3

This was further corrected for light work with the value of 0.67

460.53* 0.67 = 308.55 mg/m3.

Finally, an adjustment factor of 300 was used. 5 for interspecies, 4 for allometric scaling, 2.5 for interspecies and 6 for subacute to chroic.

308.55 mg/m3  / 300 = 1.03 mg/m3

AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
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

Workers - 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

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:
0.25 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):
600
Dose descriptor starting point:
NOAEL
Value:
0.25 mg/m³
Value:
0.25 mg/m³
Explanation for the modification of the dose descriptor starting point:

A general population long-term inhalation DNEL was developed from the reproductive NOAEL of 350 mg/kg/day from the OECD 422 study.

The dose descriptor was corrected for an inhalation exposure with the factor of 1.15 m3/kg.

350 mg/kg / 1.15 m3/kg = 304.35 mg/m3

This was further corrected for 50% oral bioavailability

304.35 mg/m3 /2 = 152.17 mg/m3

Finally, an adjustment factor of 600 was used. 10 for interspecies, 4 for allometric scaling, 2.5 for interspecies and 6 for subacute to chroic.

152.17 mg/m3  / 600 = 0.25 mg/m3

AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
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:
DNEL (Derived No Effect Level)
Value:
0.58 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):
600
Dose descriptor starting point:
NOAEL
Value:
0.58 mg/kg bw/day
Value:
0.58 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A general population long-term oral DNEL was developed from the reproductive NOAEL of 350 mg/kg/day from the OECD 422 study.

Finally, an adjustment factor of 600 was used. 10 for interspecies, 4 for allometric scaling, 2.5 for interspecies and 6 for subacute to chroic.

350 mg/kg  / 600 = 0.58 mg/kg

AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
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