Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.56 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):
25
Dose descriptor starting point:
NOAEL
Value:
66 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
114 mg/m³
Explanation for the modification of the dose descriptor starting point:

The oral NOAEL of 66 mg/kg bw/day was modified into a corrected inhalatory NOAEC as follows:

corr. NOAEC = NOAEL * ((1/0.38 m³/kg/d) * (70%/100%) * 6.7m³(8h)/10m³(8h)) * (7days/5 days) = 66 * 2.63 * 0.7 * 0.67 *1.4 = 114 mg/m³

The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m3/kg for 8 hours exposure of workers). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m3 for base level, 10 m3 for light activity). In addition, the different absorption rates (70 % via oral route and 100 % via inhalation) are taken into account. For workers, additional correction regarding exposure conditions need to be considered, inhalation exposure of workers is 5 days, whereas the NOAEL obtained in the repeated dose toxicity study has been derived from 7 days of exposure. Therefore, the NOAEL of 66 mg/kg bw has to be modified to correct these exposure condition differences as well by applying a factor of 1.4.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for extrapolation from a sub-chronic to a chronic duration
AF for interspecies differences (allometric scaling):
1
Justification:
Default; in case of route-to-route extrapolation from an oral NOAEL to an corrected inhalation NOAEC no factor for allometric scaling needs to be applied
AF for other interspecies differences:
2.5
Justification:
Default; If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part).
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
The database is considered reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.285 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.47 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):
100
Dose descriptor starting point:
NOAEL
Value:
66 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
647 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL obtained in an oral repeated dose toxicity study has been modified into a corrected dermal NOAEL as follows

corr. NOAEL = NOAEL * (70 %/10 %) * (7days/5days) = NOAEL * 7 * 1.4 = 66 mg/kg bw/day * 10 * 1.4 = 647 mg/kg bw/day

The NOAEL of 66 mg/kg bw was modified to correct differences in absorption rates between dermal and oral absorption (10 % dermal absorption and 70 % oral absorption). For workers, additional correction regarding exposure conditions need to be considered, inhalation exposure of workers is 5 days, whereas the NOAEL obtained in the repeated dose toxicity study has been derived from 7 days of exposure. Therefore, the NOAEL of 66 mg/kg bw has to be modified to correct these exposure condition differences as well by applying a factor of 1.4.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for extrapolation from a sub-chronic to a chronic duration
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for allometric scaling (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default; If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part).
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.47 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic dermal effects was considered sufficiently protective for acute dermal exposure.

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The registered uses do not lead to any exposure of the general population, so that no DNELs for the general population were derived.

Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The registered uses do not lead to any exposure of the general population, so that no DNELs for the general population were derived.

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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The registered uses do not lead to any exposure of the general population, so that no DNELs for the general population were derived.

Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The registered uses do not lead to any exposure of the general population, so that no DNELs for the general population were derived.

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The registered uses do not lead to any exposure of the general population, so that no DNELs for the general population were derived.

Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The registered uses do not lead to any exposure of the general population, so that no DNELs for the general population were derived.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population