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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.6 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):
30
Modified dose descriptor starting point:
NOAEC
Value:
528 mg/m³
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
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 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):
150
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Acute/short term exposure
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

DNEL Workers

 

DNEL Long-term - inhalation, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 300 mg/kg bw/day in rats in chronic oral toxicity study

 

Correction of starting point:

Differences in respiratory volumes: respiratory volume of the rat in 8 h corresponds to 0.38 m3/kg bw, additional correction for the higher standard respiratory volumes of workers compared to resting persons: correction factor = (1 ÷ 0.38) * (6.7 ÷ 10) = 1.76

Overall correction factor: 1.76

Corrected starting point: 300 * 1.76 = 528 mg/m3

 

Assessment factors relating to the extrapolation procedure:

Interspecies: not considered, as an allometric scaling is not applied in the case of systemic effects after inhalation

Intraspecies: 5 (default assessment factor)

Time extrapolation: 1 (default assessment factor)

Route to route extrapolation: 2 (default assessment factor)

Dose-response: 1 (default assessment factor)

Quality of whole database: 3 (older study, not all standard endpoints investigated)

Overall assessment factor: 5 * 1 * 2 * 1 * 3 = 30

 

DNEL Long-term - inhalation, systemic effects: 528 mg/m3 ÷ 30 = 17.6 mg/m3

 

 

DNEL Long-term - dermal, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 300 mg/kg bw/day in rats in chronic oral toxicity study

 

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 * 2.5 (default assessment factors)

Intraspecies: 5 (default assessment factor)

Time extrapolation: 1 (default assessment factor)

Route to route extrapolation: 1 (default assessment factor)

Dose-response: 1 (default assessment factor)

Quality of whole database: 3 (older study, not all standard endpoints investigated)

Overall assessment factor: 4 * 2.5 * 5 * 1 * 1 * 1 * 3 = 150

 

DNEL Long-term - dermal, systemic effects: 300 mg/kg bw/day ÷ 150 = 2 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.4 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):
60
Modified dose descriptor starting point:
NOAEC
Value:
261 mg/m³
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
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 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
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Acute/short term exposure
DNEL related information

Local effects

Long 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:
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):
300
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

DNEL General Population

 

DNEL Long-term - inhalation, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 300 mg/kg bw/day in rats in chronic oral toxicity study

 

Correction of starting point:

Differences in respiratory volumes: respiratory volume of the rat in 24 h corresponds to 1.15 m3/kg bw, correction factor 1 ÷ 1.15 = 0.87

Overall correction factor: 0.87

Corrected starting point: 300 * 0.87 = 261 mg/m3

 

Assessment factors relating to the extrapolation procedure:

Interspecies: not considered, as an allometric scaling is not applied in the case of systemic effects after inhalation

Intraspecies: 10 (default assessment factor)

Time extrapolation: 1 (default assessment factor)

Route to route extrapolation: 2 (default assessment factor)

Dose-response: 1 (default assessment factor)

Quality of whole database: 3 (older study, not all standard endpoints investigated)

Overall assessment factor: 10 * 1 * 2 * 1 * 3 = 60

 

DNEL Long-term - inhalation, systemic effects: 261 mg/m3 ÷ 60 = 4.4 mg/m3

 

 

DNEL Long-term - dermal, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 300 mg/kg bw/day in rats in chronic oral toxicity study

 

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 * 2.5 (default assessment factors)

Intraspecies: 10 (default assessment factor)

Time extrapolation: 1 (default assessment factor)

Route to route extrapolation: 1 (default assessment factor)

Dose-response: 1 (default assessment factor)

Quality of whole database: 3 (older study, not all standard endpoints investigated)

Overall assessment factor: 4 * 2.5 * 10 * 1 * 1 * 1 * 3 = 300

 

DNEL Long-term - dermal, systemic effects: 300 mg/kg bw/day ÷ 300 = 1 mg/kg bw/day

 

 

DNEL Long-term - oral, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 300 mg/kg bw/day in rats in chronic oral toxicity study

 

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 * 2.5 (default assessment factors)

Intraspecies: 10 (default assessment factor)

Time extrapolation: 1 (default assessment factor)

Route to route extrapolation: not considered, as same route

Dose-response: 1 (default assessment factor)

Quality of whole database: 3 (older study, not all standard endpoints investigated)

Overall assessment factor: 4 * 2.5 * 10 * 1 * 1 * 3 = 300

 

DNEL Long-term - oral, systemic effects: 300 mg/kg bw/day ÷ 300 = 1 mg/kg bw/day