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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.58 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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
264.47 mg/m³
Explanation for the modification of the dose descriptor starting point:

As no long-term study on inhalation is available, route-to-route extrapolation has been performed (oral to inhalation).


The NOAEL (oral route) observed in an Extended One-Generation Reproductive Toxicity Study, performed according to OECD 443 guideline (Barraclough, 2021), was used to derive a DNEL long-term, systemic effects via the inhalation route. The NOAEL was established to be 150 mg/kg bw/day.


The oral NOAEL dose in rats is converted to the corresponding air concentrations using a standard breathing volume for the rat (0.38 m³/kg bw for 8 hours, as this is the expected duration of worker exposure). The resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity for workers. This correction factor is derived from the inhaled volumes during an 8-hour period under the respective conditions (6.70 m³ for base level, 10 m³ for light activity). No correction factor for bioavailability is required as bioavailability after oral and inhalatory administration is assumed to be 100%. The corrected inhalation NOAEC is calculated as follows: 150 mg/kg bw/day x (1/(0.38 m³/kg bw/day)) x (6.70 m³/10 m³) = 264.47 mg/m³.


 


 

AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
difference in study duration, subchronic (121 days) to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Covered by calculation for route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Default assessment factor for worker population
AF for the quality of the whole database:
1
Justification:
Default assessment factor
AF for remaining uncertainties:
1
Justification:
Default assessment factor
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:
15 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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As no long-term study via dermal application is available, route-to-route extrapolation has been performed (oral to dermal).


The NOAEL (oral route) observed in an Extended One-Generation Reproductive Toxicity Study, performed according to OECD 443 guideline (Barraclough, 2021), was used to derive a DNEL long-term, systemic effects via the dermal route. The NOAEL was established to be 150 mg/kg bw/day. After route-to-route extrapolation from oral to dermal, the dose descriptor starting point is 150 mg/kg bw/day x 100%/10% = 1500 mg/kg bw/day. A correction factor of 10 is considered as bioavailability after oral administration is established to be 100%, and after dermal administration 10%. 

AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
difference in study duration, subchronic (121 days) to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

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:
DNEL (Derived No Effect Level)
Value:
2.61 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:
150 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
130.43 mg/m³
Explanation for the modification of the dose descriptor starting point:

This route is considered of minor concern due to the low vapour pressure of the substance. In addition, the substance is marketed as a water solution.


As no long-term study on inhalation is available, route-to-route extrapolation has been performed (oral to inhalation). 


The NOAEL (oral route) observed in an Extended One-Generation Reproductive Toxicity Study, performed according to OECD 443 guideline (Barraclough, 2021), was used to derive a DNEL long-term, systemic effects via the inhalation route. The NOAEL was established to be 150 mg/kg bw/day.


The oral NOAEL dose in rats is converted to the corresponding air concentrations using a standard breathing volume for the rat (1.15 m³/kg for 24 hours as this is the expected duration exposure for consumers). No correction factor for bioavailability is required as bioavailability after oral and inhalatory administration is assumed to be 100%. The corrected inhalation NOAEC is calculated as follows: 150 mg/kg bw/day x 1/(1.15 m³/kg bw/day) = 130.43 mg/m³.

AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point, no additional assessment factor is required.
AF for differences in duration of exposure:
2
Justification:
difference in study duration, subchronic (121 days) to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Covered by calculation for route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
Default assessment factor
AF for remaining uncertainties:
1
Justification:
Default assessment factor
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:
7.5 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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As no long-term study via dermal application is available, route-to-route extrapolation has been performed (oral to dermal).


The NOAEL (oral route) observed in an Extended One-Generation Reproductive Toxicity Study, performed according to OECD 443 guideline (Barraclough, 2021), was used to derive a DNEL long-term, systemic effects via the dermal route. The NOAEL was established to be 150 mg/kg bw/day. After route-to-route extrapolation from oral to dermal, the dose descriptor starting point is 150 mg/kg bw/day x 100%/10% = 1500 mg/kg bw/day. A correction factor of 10 is considered as bioavailability after oral administration is established to be 100%, and after dermal administration 10%.

AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
difference in study duration, subchronic (121 days) to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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:
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:
0.75 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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No correction is needed for route-to-route extrapolation in this case. The NOAEL (oral route) observed in an Extended One-Generation Reproductive Toxicity Study, performed according to OECD 443 guideline (Barraclough, 2021), was used to derive a DNEL long-term, systemic effects via the oral route. The NOAEL was established to be 150 mg/kg bw/day. 

AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
difference in study duration, subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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

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