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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:
17.3 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):
50
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
216.29 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the evaluation of the long-term, systemic, inhalation of workers, the most sensitive endpoint was repeated dose toxicity via the inhalation route. A chronic NOAEC value of 0.13 mg/m3 to rats was obtained in the sub-chronic study conducted on SC07. Considering the vapour pressure of the SC07 and the target substance, it is observed that the SC07 is more available as a vapour and therefore a conservative approach would be followed in case the study on SC07 is used. For this reason, a study on a structural analogue (SC01) with a more similar vapour pressure is used for the calculation of the DNEL via inhalation. More specifically, a chronic study via the oral route (103 weeks) on rats is used. The NOAEL was found to be 50 mg/kg bw/day for female rats. Considering that the study was performed on a structural analogue, the NOAEL is readjusted to the substance dose, resulting as 88.28 mg/kg bw/day.

Route-to-route extrapolation is therefore needed from the oral to the inhalation route.

The NOAEL rat is converted to NOAEL human by dividing with the allometric scalling factor 4 for interspecies differences. By multiplying the NOAEL human with the default human body weight (70 kg) and dividing the default human breathing volume referring to workers (10 m3in 8h and light activity), this dose is then translated into an air concentration. The absorption rate for human via inhalation is not known for the substance. It is assumed that absorption rate via inhalation route is similar to absorption rate via oral route.

NOAELoral= 88.28 mg/kg b.w

Standard human body weight = 70 kg

Default human breathing volume for workers in 8 hours = 10 m3

A worker is considered to be exposed to 10 m3 for 8 hours per day for 5 days out of 7, therefore, the NOAEC value is multiplied by 10 m3and a factor of 1.4 to account for the length of a work day and for weekends.

Therefore, NOAECinh= (88.28/4)* (70/10)*1.4 = 216.29 mg/m3

AF for dose response relationship:
1
Justification:
Dose response relationship observed
AF for differences in duration of exposure:
1
Justification:
An adequate chronic toxicity study is available
AF for interspecies differences (allometric scaling):
1
Justification:
The allometric scaling is already considered
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)
AF for intraspecies differences:
5
Justification:
AF for intraspecies differences is considered 5 to allow for potential differences in the population of workers
AF for the quality of the whole database:
1
Justification:
Good standard of quality of database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
low 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:
2.29 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:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
229.27 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long-term exposure data is available for the dermal route, however, due to the limitations of the available study the NOAEL is not considered for the calculation of the DNEL. Instead, the NOAEL value used resulted from an animal study whereby the substance was administered orally to rats for 90 days (sub-chronic study) conducted according to a guideline equivalent to the OECD 408. Route-to-route extrapolation is therefore needed from the oral to the dermal route. The most sensitive value was identified in the Repeated Dose Toxicity endpoint: the NOAEL for oral, sub-chronic toxicity was set at 125 mg/kg bw/day. The following calculation was performed:

- A worker is considered to be exposed to a substance for 5 days out of 7, whereas the test animals are exposed to the substance for 7 days, therefore, the NOAEL value is multiplied by a factor of 1.4.

- The skin absorption value is automatically allocated as 100 % as it satisfies both of the requirements: partition coefficient value from -1 to 4 (log POW = 1.81); and/or molecular weight below 500 Da (molecular weight = 194.2 Da).

Considering that the study was performed on a structural analogue, the NOAEL is readjusted to the substance dose, resulting as 163.76 mg/kg bw/day.

Based on these considerations, the following formula is applied:

NOAELhuman, dermal = NOAELrat, oral × 1.4 / 100 %

Considering the sub-chronic NOAEL value to rats via the oral route was set at 163.76 mg/kg bw/day, the sub-chronic NOAEL for humans via the dermal route is 229.27 mg/kg bw/day.

Subsequent assessment factors (AF) are then applied as detailed below. The overall assessment factor was found to be 100.

AF for dose response relationship:
1
Justification:
Dose response relationship observed
AF for differences in duration of exposure:
2
Justification:
An assessment factor of 2 is applied to allow for differences between a sub-chronic and chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
An assessment factor of 4 allows for differences between rats and humans
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)
AF for intraspecies differences:
5
Justification:
AF for intraspecies differences is considered 5 to allow for potential differences in the population of workers
AF for the quality of the whole database:
1
Justification:
Good standard of quality of database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.65 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:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
66.21 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the evaluation of the long-term, systemic, inhalation of workers, the most sensitive endpoint was repeated dose toxicity via the inhalation route. A chronic NOAEC value of 0.13 mg/m3to rats was obtained in the sub-chronic study conducted on SC07. Considering the vapour pressure of the SC07 and the target substance, it is observed that the SC07 is more available as a vapour and therefore a conservative approach would be followed in case the study on SC07 is used. For this reason, a study on a structural analogue (SC01) with a more similar vapour pressure is used for the calculation of the DNEL via inhalation. More specifically, a chronic study via the oral route (103 weeks) on rats is used. The NOAEL was found to be 50 mg/kg bw/day for female rats.

Considering that the study was performed on a structural analogue, the NOAEL is readjusted to the substance dose, resulting as 88.28 mg/kg bw/day.

Route-to-route extrapolation is therefore needed from the oral to the inhalation route.

The NOAEL rat is converted to NOAEL human by dividing with the allometric scalling factor 4 for interspecies differences. By multiplying the NOAEL human with the default human body weight (60 kg) and dividing the default human breathing volume referring to general population (20 m3 for 20 h and light activity), this dose is then translated into an air concentration. The absorption rate for human via inhalation is not known for the substance. It is assumed that absorption rate via inhalation route is similar to absorption rate via oral route.

NOAELoral= 88.28 mg/kg b.w

Standard human body weight = 60 kg

Default human breathing volume for workers in 8 hours = 10 m3

Therefore, NOAECinh= (88.28/4)* (60/20) = 66.21 mg/m3

AF for dose response relationship:
1
Justification:
Dose response relationship observed
AF for differences in duration of exposure:
1
Justification:
An adequate chronic toxicity study is available
AF for interspecies differences (allometric scaling):
1
Justification:
The allometric scaling is already considered
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)
AF for intraspecies differences:
10
Justification:
AF for intraspecies differences is considered 10 to allow for potential differences in the general population such as age, health, race
AF for the quality of the whole database:
1
Justification:
Good standard of quality of database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.819 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):
200
Dose descriptor starting point:
NOAEL
Value:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
163.76 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long-term exposure data is available for the dermal route, however, due to the limitations of the available study the NOAEL is not considered for the calculation of the DNEL. Instead, the NOAEL value used resulted from an animal study whereby the substance was administered orally to rats for 90 days (sub-chronic study) conducted according to a guideline equivalent to the OECD 408. Route-to-route extrapolation is therefore needed from the oral to the dermal route. The most sensitive value was identified in the Repeated Dose Toxicity endpoint: the NOAEL for oral, sub-chronic toxicity was set at 125 mg/kg bw/day. The following calculation was performed:

- The skin absorption value is automatically allocated as 100 % as it satisfies both of the requirements: partition coefficient value from -1 to 4 (log POW= 1.81); and/or molecular weight below 500 Da (molecular weight = 194.2 Da).

Considering that the study was performed on a structural analogue, the NOAEL is readjusted to the substance dose, resulting as 163.76 mg/kg bw/day.

Based on these considerations, the following formula is applied:

NOAELhuman, dermal = NOAELrat, oral / 100 %

Considering the sub-chronic NOAEL value to rats via the oral route was set at 163.76 mg/kg bw/day, the sub-chronic NOAEL for humans via the dermal route is unchanged.

Subsequent assessment factors (AF) are then applied as detailed below. The overall assessment factor was found to be 200.

AF for dose response relationship:
1
Justification:
Dose response relationship observed
AF for differences in duration of exposure:
2
Justification:
An assessment factor of 2 is applied to allow for differences between a sub-chronic and chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
An assessment factor of 4 allows for differences between rats and humans
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)
AF for intraspecies differences:
10
Justification:
AF for intraspecies differences is considered 10 to allow for potential differences in the general population such as age, health, race
AF for the quality of the whole database:
1
Justification:
Good standard of quality of database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
0.819 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):
200
Dose descriptor starting point:
NOAEL
Value:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
163.76 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL value used resulted from an animal study whereby the substance was administered orally to rats for 90 days (sub-chronic study); the most sensitive value was identified in the Repeated Dose Toxicity endpoint: the NOAEL for oral, sub-acute toxicity was set at 125 mg/kg bw/day. Readjusting the NOAEL to the substance dose, the NOAEL results as 163.76 mg/kg bw/day.

No route-to-route extrapolation is required.

Subsequent assessment factors (AF) are then applied as detailed below. The overall assessment factor was found to be 200.

AF for dose response relationship:
1
Justification:
Dose response relationship observed
AF for differences in duration of exposure:
2
Justification:
An assessment factor of 2 is applied to allow for differences between a sub-chronic and chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
An assessment factor of 4 allows for differences between rats and humans
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)
AF for intraspecies differences:
10
Justification:
AF for intraspecies differences is considered 10 to allow for potential differences in the general population such as age, health, race
AF for the quality of the whole database:
1
Justification:
Good standard quality of database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
medium hazard (no threshold derived)

Additional information - General Population