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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.93 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):
75
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
370 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects through long-term exposure via inhalation is derived from a sub-acute repeated dose toxicity study. The NOAEL of this rat study with oral treatment was 300 mg/kg bw for fertility effects. This value was modified to a worker 8h-NOAEC of (according to 'Example R.8-2 Workers' of the 'Guidance on information requirements and chemical safety assessment: Chapter 8'.) using an allometric scaling factor of 4 for rats. The oral dose for the rat was converted to the corresponding air concentration using a standard breathing volume for the rat (0.2l/min/kg bw * 4 * 60 * 8 = 0.38 m3/kg bw for 8 hour exposure) by 300mg/kg bw/0.38 m3/kg bw = 789 mg/m3. It was then adjusted for the difference between basic caloric demand and caloric demand under light activity, as relevant for workers: 789 mg/m3 * 6.7m3/10m3 = 529 mg/m3.

Further, the difference between daily exposure in the study and 5 days/week of worker exposure was accounted for by the factor of 7/5=1.4 and it was conservatively assumed that the absorption is 50% when ingested, but 100% when inhaled, resulting in a factor of 0.5.

Applying these additional factors, the modified starting point was obtained as 529 mg/m3 * 1.4 * 0.5 = 370 mg/m3.

AF for dose response relationship:
1
Justification:
As no extrapolation of effects was needed, no assessment factor was applied for the dose-response relationship.
AF for differences in duration of exposure:
6
Justification:
Standard factor for extrapolation from sub-acute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
No factor required.
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Standard factor for intraspecies differences for workers.
AF for the quality of the whole database:
1
Justification:
The only available relevant study is of high quality.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.93 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects through long-term inhalation exposure was considered sufficiently protective for acute exposure.

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
10 mg/m³
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:
1.4 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
420 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic dermal effects through long-term exposure was derived from a sub-acute repeated dose toxicity study. The NOAEL of this rat study with oral treatment was 300 mg/kg bw.

This value was modified to a dermal NOAEL by conservatively assuming that human dermal absorption is equal to oral absorption in rats.

Further, the difference between daily exposure in the study and 5 days/week of worker exposure was accounted for by the factor of 7/5=1.4, resulting in a modified starting point of 420 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
As no extrapolation of effects was needed, no assessment factor was applied for the dose-response relationship.
AF for differences in duration of exposure:
6
Justification:
Standard factor for extrapolation from sub-acute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor from rats to humans.
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining differences.
AF for intraspecies differences:
5
Justification:
Standard factor for intraspecies differences for workers.
AF for the quality of the whole database:
1
Justification:
The only available relevant study is of high quality.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.4 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic dermal effects was considered sufficiently protective for acute dermal exposure.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population