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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:
24.7 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:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
617 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 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:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

DNELs based on NOAEL of 500 mg/kg bw/d obtained in the subchronic study/one generation with rats

 

Hazard conclusions for workers

Route

Type of effect

Hazard conclusion

Most sensitive endpoint

Inhalation

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

24.7mg/m³

 

effect on fertility

(Oral)

 

Dermal

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

7mg/kg bw/day

 

effect on fertility

(Oral)

 

​Correction factors:

Correction for differences in respiratory volume (workers): 2.63

Correction for differences in bioavailability (oral -> inhalation): 0.5

Correction for light activity at work: 0.67

Correction for differences between human and experimental exposure conditions (workers): 1.4

 

Inhalation Systemic effects - Long-term

DNEL derivation method: ECHA REACH Guidance

Dose descriptor starting point:NOAEL

Overall Assessment Factor:25

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):1 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:5 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

​​

Dermal Systemic effects - Long-term

DNEL derivation method: ECHA REACH Guidance

Dose descriptor starting point:NOAEL

Overall Assessment Factor:100

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):4 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:5 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

 

 

DNELs based on NOAEL of 200 mg/kg bw/d obtained in the subchronic study with beagle dogs

 

Hazard conclusions for workers

Route

Type of effect

Hazard conclusion

Most sensitive endpoint

Inhalation

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

28.9mg/m³

 

repeated dose toxicity

(Oral)

 

Dermal

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

8mg/kg bw/day

 

repeated dose toxicity

(Oral)

 

​Correction factors:

Correction for differences in respiratory volume (workers): 7.69

Correction for differences in bioavailability (oral -> inhalation): 0.5

Correction for light activity at work: 0.67

Correction for differences between human and experimental exposure conditions (workers): 1.4

 

Inhalation Systemic effects - Long-term

DNEL derivation method:

Dose descriptor starting point:NOAEL

Modified dose descriptor starting point:NOAEC

Overall Assessment Factor:25

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):1 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:5 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

​​

Dermal Systemic effects - Long-term

DNEL derivation method:

Dose descriptor starting point:NOAEL

Modified dose descriptor starting point:NOAEL

Overall Assessment Factor:35

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):1.4 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:5 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

Similar DNELs were obtained with both starting points.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.35 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:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
218 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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:
500 mg/kg bw/day
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

DNELs based on NOAEL of 500 mg/kg bw/d obtained in the subchronic study/one generation with rats

 

Hazard conclusions for the general population

Route

Type of effect

Hazard conclusion

Most sensitive endpoint

Inhalation

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

4.35mg/m³

 

effect on fertility

(Oral)

 

Dermal

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

2.5mg/kg bw/day

 

effect on fertility

(Oral)

 

Oral

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

2.5mg/kg bw/day

 

effect on fertility

(Oral)

 

Correction factors:

Correction for differences in respiratory volume (general population): 0.78

Correction for differences in bioavailability (oral -> inhalation): 0.5

Correction for differences between human and experimental exposure conditions (general population): 1

 

Inhalation Systemic effects - Long-term

DNEL derivation method: ECHA REACH Guidance

Dose descriptor starting point:NOAEL

Overall Assessment Factor:50

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):1 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:10 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

Dermal Systemic effects - Long-term

DNEL derivation method: ECHA REACH Guidance

Dose descriptor starting point:NOAEL

Overall Assessment Factor:200

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):4 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:10 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

Oral Systemic effects - Long-term

DNEL derivation method: ECHA REACH Guidance

Dose descriptor starting point:NOAEL

Overall Assessment Factor:200

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):4 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:10 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

 

 

DNELs based on NOAEL of 200 mg/kg bw/d obtained in the subchronic study with beagle dogs

Hazard conclusions for the general population

Route

Type of effect

Hazard conclusion

Most sensitive endpoint

Inhalation

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

5mg/m³

 

repeated dose toxicity

(Oral)

 

Dermal

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

2.86mg/kg bw/day

 

repeated dose toxicity

(Oral)

 

Oral

 

Systemic effects - Long-term

 

DNEL (Derived No Effect Level)

2.86mg/kg bw/day

 

repeated dose toxicity

(Oral)

 

Correction factors:

Correction for differences in respiratory volume (general population): 2.5

Correction for differences in bioavailability (oral -> inhalation): 0.5

Correction for differences between human and experimental exposure conditions (general population): 1

 

Inhalation Systemic effects - Long-term

DNEL derivation method:

Dose descriptor starting point:NOAEL

Modified dose descriptor starting point:NOAEC

Overall Assessment Factor:50

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):1 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:10 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

​​​

Dermal Systemic effects - Long-term

DNEL derivation method:

Dose descriptor starting point:NOAEL

Modified dose descriptor starting point:NOAEL

Overall Assessment Factor:70

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):1.4 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:10 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

​​

Oral Systemic effects - Long-term

DNEL derivation method:

Dose descriptor starting point:NOAEL

Modified dose descriptor starting point:NOAEL

Overall Assessment Factor:70

AF for dose response relationship:1 (Default (DNEL calculator))

AF for difference in duration of exposure:2 (Default (DNEL calculator))

AF for interspecies differences (allometric scaling):1.4 (Default (DNEL calculator))

AF for other interspecies differences:2.5 (Default (DNEL calculator))

AF for intraspecies differences:10 (Default (DNEL calculator))

AF for the quality of the whole database:1 (Default (DNEL calculator))

Similar DNELs were obtained with both starting points.