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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Acute exposure

 

The guidance on dose/concentration response regarding human health (section R8.1.2.5 of chapter R.8 of the Guidance on Information Requirements and Chemical Safety Assessment) indicates that acute DNELs do not need to be calculated for substances that are not classified for an acute toxicity hazard. As this substance is not classified, no acute DNELs need to be calculated.

 

Long-term exposure

 

- Inhalation DNEL

For deriving the inhalation DNEL regarding long-term exposure the oral 28-day study was used as starting point. Decreased urea in both sexes and increased red blood cells and hematocrit in females were observed in the oral 28-day toxicity study. A NOAEL of 285 mg/kg bw/day was established.

 

Correction of starting point from an oral study to the inhalation route:

285 mg/kg bw/day * 6.7m3/10m3 (correction for activity driven differences of respiratory volumes in workers compared to workers in rest) / 0.38 m3/kg bw (respiratory volume of rats for 8 hours exposure) / 1 (factor for route-to-route extrapolation) = 503 mg/m3

The corrected starting point for inhalation is 503 mg/m3.

 

The following assessment factors were used:

remaining differences: 1

intraspecies: 5

exposure duration: 6

quality of whole database: 1

Thus, the overall assessment factor is 30 and the DNEL for long-term exposure inhalation for workers: 17 mg/m3.

 

- Dermal DNEL

For deriving the dermal DNEL regarding long-term exposure the same starting point as used for derivation of the inhalation DNEL was used. Decreased urea in both sexes and increased red blood cells and hematocrit in females were observed in the oral 28-day toxicity study. A NOAEL of 285 mg/kg bw/day was established.

 

Correction of starting point from an oral study to the dermal route:

285 mg/kg bw/day x 1 (factor for route-to-route extrapolation) = 285 mg/kg bw/day

The corrected starting point for the dermal route is 285 mg/kg bw/day.

 

The following assessment factors were used:

interspecies: 4

remaining differences: 1

intraspecies: 5

exposure duration: 6

quality of whole database: 1

Thus, the overall assessment factor is 120 and the DNEL for long-term exposure dermal for workers: 2.4 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Acute exposure

 

The guidance on dose/concentration response regarding human health (section R8.1.2.5 of chapter R.8 of the Guidance on Information Requirements and Chemical Safety Assessment) indicates that acute DNELs do not need to be calculated for substances that are not classified for an acute toxicity hazard. As this substance is not classified, no acute DNELs need to be calculated.

 

Long-term exposure

 

- Inhalation DNEL

For deriving the inhalation DNEL regarding long-term exposure the oral 28-day study was used as starting point. Decreased urea in both sexes and increased red blood cells and hematocrit in females were observed in the oral 28-day toxicity study. A NOAEL of 285 mg/kg bw/day was established.

 

Correction of starting point from an oral study to the inhalation route:

285 mg/kg bw/day / 1.15 m3/kg bw (respiratory volume of rats for 24 hours exposure) / 1 (factor for route-to-route extrapolation) = 248 mg/m3

The corrected starting point for inhalation is 248 mg/m3.

 

The following assessment factors were used:

remaining differences: 1

intraspecies: 10

exposure duration: 6

quality of whole database: 1

Thus, the overall assessment factor is 60 and the DNEL for long-term exposure inhalation for the general population: 4 mg/m3.

 

- Dermal DNEL

For deriving the dermal DNEL regarding long-term exposure the same starting point as used for derivation of the inhalation DNEL was used. Decreased urea in both sexes and increased red blood cells and hematocrit in females were observed in the oral 28-day toxicity study. A NOAEL of 285 mg/kg bw/day was established.

 

Correction of starting point from an oral study to the dermal route:

285 mg/kg bw/day x 1 (factor for route-to-route extrapolation) = 285 mg/kg bw/day

The corrected starting point for the dermal route is 285 mg/kg bw/day.

 

The following assessment factors were used:

interspecies: 4

remaining differences: 1

intraspecies: 10

exposure duration: 6

quality of whole database: 1

Thus, the overall assessment factor is 240 and the DNEL for long-term exposure dermal for the general population: 1.2 mg/kg bw/day.

 

- Oral DNEL

For deriving the oral DNEL regarding long-term exposure the oral NOAEL of 285 mg/kg bw/day was used as starting point. Decreased urea in both sexes and increased red blood cells and hematocrit in females were observed at the highest tested dose.

 

The following assessment factors were used:

interspecies: 4

remaining differences: 1

intraspecies: 10

exposure duration: 6

quality of whole database: 1

Thus, the overall assessment factor is 240 and the DNEL for long-term exposure dermal for the general population: 1.2 mg/kg bw/day.