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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11 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:
NOAEC
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
881 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL for inhalation exposure

The relevant NOAEL for inhalation DNELs is 1000 mg/kg bw/d for Thiamine hydrochloride based on the 28-day repeated dose toxicity study (OECD422). Route-to-route extrapolation is considered using a default factor of 2 (according to the Guidance Document on Information Requirements, Chapter R8 assuming that oral absorption was at least 50 % and that 100 % of the applied dose would be absorbed by inhalation).

Worker

The NOAEL of 1000 mg Thiamine hydrochloride/kg bw/d is converted into corrected inhalatory NOAEC using the equation provided in the Guidance Document on Information Requirement, Chapter R8.

NOAEC = oral NOAEL*(1/(0.38 m3/kg/d))*(ABSoral rat/ABSinh human)*(6.7 m3(8h)/10 m3(8h)) 

It is calculated to 881 mg/m3.

Using assessment factors of (i) 5 for intraspecies extrapolation, (ii) 1 for duration exposure, and (iii) 2.5 for the remaining species differences (AF = 12.5), this results in a DNEL of 70 mg/m3for short-term exposure for workers.

Using assessment factors of (i) 5 for intraspecies extrapolation, (ii) 6 for duration exposure, and (iii) 2.5 for the remaining species differences (AF = 75), this results in a DNEL of 11 mg/m3for long-term exposure for workers.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
NA for inhalation
AF for other interspecies differences:
1
Justification:
Addressed by modification of starting point
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Data available on the test substance appropriate for the tonnage band
AF for remaining uncertainties:
1
Justification:
Default value
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:
3.3 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL for dermal exposure

Based on the general assumption that dermal absorption will not be higher than oral absorption, the relevant NOAEL for dermal DNELs is 1000 mg/kg bw/d for Thiamine hydrochloride based on the 28-day repeated dose toxicity study (OECD422) via the oral route.

Worker

Using a dermal NOAEL of 1000 mg/kg bw/day and taking into account assessment factors for (i) interspecies variation of 4, (ii) remaining species differences of 2.5, (iii) exposure duration of 6, and (iv) intraspecies variation of 5 (AF = 300), the systemic DNEL worker for long-term exposure via the dermal route is3.3 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
A clear NOAEL was obtained
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat
AF for other interspecies differences:
1
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
appropriate for the tonnage band
AF for remaining uncertainties:
2.5
Justification:
any remaining difference
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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:
2.8 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):
150
Dose descriptor starting point:
NOAEC
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
434 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL for inhalation exposure

The relevant NOAEL for inhalation DNELs is 1000 mg/kg bw/d for Thiamine hydrochloride based on the 28-day repeated dose toxicity study (OECD422). Route-to-route extrapolation is considered using a default factor of 2 (according to the Guidance Document on Information Requirements, Chapter R8 assuming that oral absorption was at least 50 % and that 100 % of the applied dose would be absorbed by inhalation).

General Population

The NOAEL of 1000 mgThiamine hydrochloride/kg bw/d is converted into corrected inhalatory NOAEC using the equation provided in the Guidance Document on Information Requirements, Chapter R8.

NOAEC = oral NOAEL*(1/(1.15 m3/kg/d))*(ABSoral rat/ABSinh human)

It is calculated to 434 mg/m3.

Using assessment factors of (i) 10 for intraspecies extrapolation, (ii) 6 for duration exposure, and (iii) 2.5 for the remaining species differences (AF = 150), this results in a DNEL of2.8 mg/m3for long-term exposure.

 

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
NA for inhalation
AF for other interspecies differences:
1
Justification:
Addressed by modification of starting point
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Data available on the test substance appropriate for the tonnage band
AF for remaining uncertainties:
1
Justification:
Default value
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:
1.6 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL for dermal exposure

Based on the general assumption that dermal absorption will not be higher than oral absorption, the relevant NOAEL for dermal DNELs is 1000 mg/kg bw/d for Thiamine hydrochloride based on the 28-day repeated dose toxicity study (OECD422) via the oral route.

General Population

Using a dermal NOAEL of 1000 mg/kg bw/day and taking into account assessment factors for (i) interspecies variation of 4, (ii) remaining species differences of 2.5, (iii) exposure duration of 6, and (iv) intraspecies variation of 10 (AF = 600), the systemic DNEL worker for long-term exposure via the dermal route is1.6 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
A clear NOAEL was obtained
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default value
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
appropriate for the tonnage band
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL for oral exposure

For Worker a DNEL for oral exposure is not considered necessary as workers are not supposed to eat at their work environment.

The relevant NOAEL for oral DNELs is 1000 mg/kg bw/d for Thiamine hydrochloride based on the 28-day repeated dose toxicity study (OECD422) via the oral route.

General Population

Using assessment factors of (i) 10 for intraspecies extrapolation, (ii) 6 for duration exposure, (iii) 4 for extrapolation from rat to human, and (iv) 2.5 for the remaining species differences (AF = 600), this results in a DNEL of1.6 mg/kg bw/dfor long-term exposure.

AF for dose response relationship:
1
Justification:
A clear NOAEL was obtained
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default value
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
appropriate for the tonnage band
AF for remaining uncertainties:
1
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

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