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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.9 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:
84.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
294.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no adequate experimental data on the repeated dose toxicity by the inhalation route available. Therefore, the worker-DNEL long-term for the inhalative route - systemic is derived from the oral NOAEL of 84.1 mg/kg bw/day, obtained in the key Repeated Dose Toxicity Study (similar to OECD TG 409) in Beagle dogs. The NOAECcorr. is calculated as follows:

- respiratory volume dog (8h exposure): 0.134m³/kg/8h

- respiratory volume workers in rest compared to workers in light activity (8h): 6.7 m³/10 m³

- absorption (oral, dog) = 50 % (default)

- absorption (inhalation, human) = 100 % (default)

- experimental exposure time = 7 days/week

- exposure time worker = 5 days/week

--> modified dose descriptor (corrected NOAEC) = 84.1 mg/kg bw/day * (1/0.134 m³/kg) * (6.7 m³/10 m³) * (50 %/100 %) * (7 d/5 d) = 294.4 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The recommended AF for the extrapolation from sub-chronic to chronic exposure is applied.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is part of the route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
3
Justification:
An additional factor of 3 is applied for using a read-across approach
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:
DNEL (Derived No Effect Level)
Value:
1.1 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):
105
Dose descriptor starting point:
NOAEL
Value:
84.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
118 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no adequate experimental data on the dermal route available. The dermal route is typically covered by oral route information in the absence of data for this administration route. Since no data on penetration through skin are available, the NOAEL is not adjusted for dermal penetration properties. The DNEL is derived from the oral NOAEL of 84.1 mg/kg bw/day, obtained in the key Repeated Dose Toxicity Study (similar to OECD TG 409) in Beagle dogs. The NOAELcorr. is calculated as follows:

- absorption (oral, dog) = 50 % (default)

- absorption (dermal, human) = 50 % (default)

- experimental exposure time = 7 days/week

- exposure time worker = 5 days/week

--> modified dose descriptor (corrected dermal NOAEL) = 84.1 mg/kg bw/day * (50 %/50 %) * (7 d/5 d) = 118 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
Assessment factor of 2 is applied since the DNEL is derived from a subchronic study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
The default allometric scaling factor for the differences between dogs and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
3
Justification:
An additional factor is applied for using a read-across.
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

Identification of relevant dose descriptor

No repeated dose data is available with the test item. The 90-day toxicity study performed in Beagle dogs with a structural analogue was chosen as the most relevant study for safety assessment. In this study, groups of six male and female dogs were treated with the read-across substance continuously in feed. No treatment-related adverse effects have been observed up to the highest dose tested, thus a NOAEL of 84.1 (males) and 90.2 mg/kg body weight per day (females), was established. For derivation of DNELs, the lower value of 84.1 mg/kg was selected as calculation starting point.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.68 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:
84.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
102 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no adequate experimental data on the repeated dose toxicity by the inhalation route available. Therefore, the worker-DNEL long-term for the inhalative route - systemic is derived from the oral NOAEL of 84.1 mg/kg bw/day, obtained in the key Repeated Dose Toxicity Study (similar to OECD TG 409) in Beagle dogs. The NOAECcorr. is calculated as follows:

- respiratory volume dog (24h exposure): 0.403 m³/kg/8h

- absorption (oral, dog) = 50 % (default)

- absorption (inhalation, human) = 100 % (default)

--> modified dose descriptor (corrected NOAEC) = 84.1 mg/kg bw/day * (1/0.403 m³/kg) * (50 %/100 %) = 102 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The recommended AF for the extrapolation from sub-chronic to chronic exposure is applied.
AF for interspecies differences (allometric scaling):
1.4
Justification:
An allometric scaling factor for dogs is used to take tribute to the interspecies differences in the metabolic rate.
AF for other interspecies differences:
2.5
Justification:
A default factor for remaining uncertainties is used.
AF for intraspecies differences:
10
Justification:
The default value for the relatively heterogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
3
Justification:
An additional factor for using a read-across is applied
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:
DNEL (Derived No Effect Level)
Value:
0.4 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):
210
Dose descriptor starting point:
NOAEL
Value:
84.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
84.1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no adequate experimental data on the dermal route available. Therefore, the general population-DNEL long-term for dermal route - systemic is derived from the oral NOAEL of 84.1 mg/kg bw/day, obtained in the key Repeated Dose Toxicity Study (OECD TG 409) in Beagle dogs. The NOAELcorr. is calculated as follows:

- absorption (oral, dog) = 50 % (default)

- absorption (dermal, human) = 50 % (default)

- experimental exposure time = 7 days/week

- exposure time general population= 7 days/week

--> modified dose descriptor (corrected dermal NOAEL) = 84.1 mg/kg bw/day * (50 %/50 %) * (7 d/7 d) = 84.1 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
Assessment factor of 2 is applied since the DNEL is derived from a subchronic study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the general population is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
3
Justification:
An additional factor accounting for a read-across is applied
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:
0.4 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):
210
Dose descriptor starting point:
NOAEL
Value:
84.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
84.1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The general-population DNEL long-term for oral route - systemic is derived from the oral NOAEL of 84.1 mg/kg bw/day, obtained in the key Repeated Dose Toxicity Study (similar to OECD TG 409) in Beagle dogs. The NOAELcorr. is calculated as follows:

- absorption (oral, dog) = 50 % (default)

- absorption (oral, human) = 50 % (default)

- experimental exposure time = 7 days/week

- exposure time worker = 7 days/week

--> modified dose descriptor (corrected dermal NOAEL) = 84.1 mg/kg bw/day * (50 %/50 %) * (7 d/7 d) = 84.1 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
Assessment factor of 2 is applied since the DNEL is derived from a subchronic study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
The default allometric scaling factor for the differences between dogs and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the general population is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
3
Justification:
An additional factor for using a read-across was applied
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

Identification of relevant dose descriptor

The dose descriptor chosen is the same as for workers (see above). The NOAEL of 84 mg/kg observed in the 90-day repeated dose study in dogs with a structural analogue was used as starting point to derive the DNELs.