Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.76 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):
75
Dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Value:
432 mg/m³
Explanation for the modification of the dose descriptor starting point:

NAEC is the modified starting point; 350 mg/kg bw/day is the NOAEL for repeated dose toxicity; 0.38 m³/kg bw is the default respiratory volume for the rat corresponding to the daily duration of human exposure. 0.67 is correction for the difference between respiratory rates under standard conditions and under conditions of light activity, considering the inhalation volumes for workers in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity); 1.4 is correction for the differences between animal and workers exposure conditions (i.e. 7 days/5 days); 0.5 is correction for differences in bioavailability

AF for dose response relationship:
1
Justification:
Default: data well supported
AF for differences in duration of exposure:
6
Justification:
Default: subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default: scaling issues considered in modified starting point
AF for other interspecies differences:
2.5
Justification:
Default: remaining differences
AF for intraspecies differences:
5
Justification:
Default: worker population
AF for the quality of the whole database:
1
Justification:
Default: good quality and reliability
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:
1.63 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):
300
Dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Value:
490 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NAEC is the modified starting point; 350 mg/kg bw is the NOAEL for repeated dose toxicity; 1.4 is correction for the differences between animal and workers exposure conditions (i.e. 7 days/5 days). Based on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor for bioavailability should be introduced when performing oral-to-dermal extrapolation

AF for dose response relationship:
1
Justification:
Default data well supported
AF for differences in duration of exposure:
6
Justification:
Default subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric factor rat to man
AF for other interspecies differences:
2.5
Justification:
Default remaining differences
AF for intraspecies differences:
5
Justification:
Default worker population
AF for the quality of the whole database:
1
Justification:
Default good quality and reliability
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The Derived No Effect Levels for both inhalation and dermal long-term exposure, systemic effects, are estimated on the basis of the No Observed Effect Level obtained in the subacute combined repeated with the reproduction/developmental toxicity screening test in Rats (Pasics Szakonyiné, 2018).

The NOAEL was established as equal/higher than 350 mg/kg body weight/day for systemic toxicity, as well as for reproductive and developmental toxicity.

The calculation of DNELs is based on the NOAEL identified, which should be corrected for the differences between effect assessment data and the real human exposure situation, taking into account variability and uncertainty within and between species. In order to correct the interspecies difference between rat and human the No Observed Adverse Effect Level has to be corrected, using the default values for DNEL calculation.

No DNEL is derived for inhalation acute exposure, systemic effects, based on the physical state of the substance, inhalation is not an appropriate route of exposure. In addition, no DNEL is derived is derived for both long-term/acute local effects because significant exposure is unlikely to occur due to RMM and OCs.

No DNEL is derived for dermal acute exposure, systemic effects, because no acute toxicity potential was observed up to 2000 mg/kg bw; details in the acute toxicity endpoint summary.

Since no substance-related local effects were observed, only the DNEL for long-term dermal systemic effects were derived.

 

Regarding the hazard for eyes, the substance can be considered as low hazardous, based on the indication given in the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Part E: Risk Characterisation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.02 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):
150
Dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Value:
152 mg/m³
Explanation for the modification of the dose descriptor starting point:

NAEC m3/kg is the modified starting point; 350 mg/kg bw/day is the NOAEL for repeated dose toxicity; 1.15 m3/kg is correction for 24 hours exposure of general public; 0.5 is correction for differences in bioavailability

AF for dose response relationship:
1
Justification:
Default data well supported
AF for differences in duration of exposure:
6
Justification:
Default subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default scaling issues considered in modified starting point
AF for other interspecies differences:
2.5
Justification:
Default remaining differences
AF for intraspecies differences:
10
Justification:
Default general population
AF for the quality of the whole database:
1
Justification:
Default good quality and reliability
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:
0.583 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):
600
Dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Value:
350 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor for bioavailability should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:
1
Justification:
Default data well supported
AF for differences in duration of exposure:
6
Justification:
Default subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric factor rat to man
AF for other interspecies differences:
2.5
Justification:
Default remaining differences
AF for intraspecies differences:
10
Justification:
Default general population
AF for the quality of the whole database:
1
Justification:
Default good quality and reliability
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.583 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):
600
Dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Value:
350 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The modification of dose description is not necessary.

AF for dose response relationship:
1
Justification:
Default data well supported
AF for differences in duration of exposure:
6
Justification:
Default subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric factor rat to man
AF for other interspecies differences:
2.5
Justification:
Default remaining differences
AF for intraspecies differences:
10
Justification:
Default general population)
AF for the quality of the whole database:
1
Justification:
Default good quality and reliability
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

The Derived No Effect Levels for inhalation, dermal and oral long-term exposure, systemic effects, are estimated on the basis of the No Observed Effect Level obtained in the subacute combined repeated with the reproduction/developmental toxicity screening test in Rats (Pasics Szakonyiné, 2018).

The NOAEL was established as equal/higher than 350 mg/kg body weight/day for systemic toxicity, as well as for reproductive and developmental toxicity.

The calculation of DNELs is based on the NOAEL identified, which should be corrected for the differences between effect assessment data and the real human exposure situation, taking into account variability and uncertainty within and between species. In order to correct the interspecies difference between rat and human the No Observed Adverse Effect Level has to be corrected, using the default values for DNEL calculation.

 

For general population, no DNEL is derived for inhalation acute exposure, systemic effects, as well as no DNEL is derived for long-term/acute local effects because, based on the physical state of the substance, inhalation is not an appropriate route of exposure.

No DNEL is derived for either oral or dermal acute exposure, systemic effects, because no acute toxicity potential was observed up to 2000 mg/kg bw of both oral/dermal exposure; details in the acute toxicity endpoint summary.

Since no substance-related local effects were observed, only the DNEL for dermal long-term systemic effects was derived.

 

Regarding the hazard for eyes, the substance can be considered as low hazardous, based on the indication given in the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Part E: Risk Characterisation.