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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:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
276.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeat dose toxicity data were available for ethanethiol. However, a key read across study (Ulrich, 1982) was available for butane-1-thiol. Both butane-1-thol and ethanethiol are members of the C2-C4 aliphatic thiols category. In this 90-day inhalation study, the repeated dose toxicity of butane-1-thiol was investigated in Sprague-Dawley rats. The NOAEC was identified to be 550 mg/m3 based on the absence of systemic toxicity effects at the highest concentration tested.
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default (remaining differences)
AF for intraspecies differences:
5
Justification:
ECHA default (workers)
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECHA default
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:
1.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
159.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No dermal repeat dose toxicity data were available for ethanethiol. One oral read across study (MHLW, 2006; Klimisch score = 2) of 2 -methylpropane-2-thiol has been performed but not used in the derivation of this DNEL because the exposure period was subacute. Therefore, read across inhalation data (Ulrich, 1982) from butane-1-thiol was used by performing a route-to-route extrapolation. The NOAEC used was 550 mg/m3 based on the absence of systemic toxicity effects at the highest concentration tested..
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default (rat to human)
AF for other interspecies differences:
2.5
Justification:
ECHA default (remaining differences)
AF for intraspecies differences:
5
Justification:
ECHA default (workers)
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECHA default
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:
no hazard identified

Additional information - workers

Long-term exposure – Systemic effects:

 

1) Dermal DN(M)EL:

Step 1) Relevant dose-descriptor

NOAEC6h/rat: 0.55 mg/L

Step 2) Modification of starting point

Conversion for units:

0.55 mg/L x 1000 = 550 mg/m3

Correction of rat inhalation NOAEC to rat dermal NOAEL – correction for respiratory volume and for difference in absorption rates

NOAELrat: 159.5 mg/kg bw/day

(= 550 x 0.29* x 1)

Assumption: Based on ECHA guidance (Chapter R.8) no default factor was applied for differences in absorption in rats and humans and therefore absorption was assumed to be 100% via the dermal and inhalation route

*Respiration rate in rats for 6 hour exposure

Step 3) Assessment factors

ECHA assessment factors used

Interspecies (allometric scaling)

4 (rat)

Interspecies

2.5 (for systemic effects)

Intraspecies

5 (for worker population)

Exposure duration

2 (for sub-chronic to chronic)

Dose response

1

Quality of database

1

Total Assessment Factors

100

Worker DNELlong-term for dermal route -Systemic

1.6(= 159.5 x 1/(4 x 2.5 x 5 x 2 x 1 x 1))

2) Inhalation DN(M)EL:

Step 1) Relevant dose-descriptor

NOAEC6h/rat: 0.55 mg/L
Step 2) Modification of starting point  Conversion for units:0.55mg/L x 1000 = 550 mg/m3
Correction of exposure duration in study  (6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/ week)
Correction for activity driven differences of respiratory volumes in workers compared to workers in rest 6.7 m3/10 m3Corrected NOAEC = 276.4 mg/m3(= 550 x 6/8 x 6.7/10)
Step 3) Assessment factors ECHA assessment factors used 
 Interspecies 2.5 (for systemic effects) 
 Intraspecies 5 (for workers) 
 Exposure duration 2 (for sub-chronic to chronic) 
 Dose response
 Quality of database  1
 Total Assessment Factors 25 
 Worker DNELlong-term for inhalation route -Systemic

11 mg/m3

(= 276.4 x 1/(2.5 x 5 x 2 x 1 x 1))

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.96 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
98.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeat dose toxicity data were available for ethanethiol. However, a key read across study (Ulrich, 1982) was available for butane-1-thiol, a structural analogue of ethanethiol. In this 90-day inhalation study, the repeated dose toxicity of butane-1-thiol was investigated in Sprague-Dawley rats. The NOAEC was identified to be 550 mg/m3 based on the absence of systemic toxicity effects at the highest concentration tested..
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default (remaining differences)
AF for intraspecies differences:
10
Justification:
ECHA default (general population)
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECHA default
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:
no hazard identified
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:
0.8 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
159.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No oral repeat dose toxicity data was available for ethanethiol. One key read across study (MHLW, 2006; Klimisch score = 1) of 2-methylpropane-2-thiol has been performed but not used in the derivation of this DNEL because it was a subacute study that only tested up to a maximum dose of 200 mg/kg bw/day and no adverse effects were recorded. Therefore in the absence of suitable oral data, key read across inhalation data (Ulrich, 1992) from butane-1-thiol (structural analogue) was used by performing a route-to-route extrapolation. The NOAEC used was 550 mg/m3 based on the absence of systemic toxicity effects at the highest concentration tested..
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default (rat to human)
AF for other interspecies differences:
2.5
Justification:
ECHA default (remaining differences)
AF for intraspecies differences:
10
Justification:
ECHA default (general population)
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECHA default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Long-term exposure – Systemic effects:

 

2) Inhalation DN(M)EL:

Step 1) Relevant dose-descriptor

NOAEC6h/rat: 0.55 mg/L
Step 2) Modification of starting point  Conversion for units: 0.55 mg/L x 1000 = 550 mg/m3
Correction of exposure duration in study  (6 hrs/day, 5 days/week) to default general population exposure (24 hrs/day, 7 days/ week) Corrected NOAEC = 98.2 mg/m3(= 550 x 6/24 x 5/7)
Step 3) Assessment factors ECHA assessment factors used 
 Interspecies 2.5 (for systemic effects) 
 Intraspecies 10 (for general population) 
 Exposure duration 2 (for sub-chronic to chronic) 
 Dose response
 Quality of database 1
 Total Assessment Factors 50 
General Population DNELlong-term for inhalation route -Systemic

1.96 mg/m3

(= 98.2 x 1/(2.5 x 10 x 2 x 1 x 1))

3) Oral DN(M)EL:

 

Step 1) Relevant dose-descriptor

 NOAEC6h/rat: 0.55 mg/L
Step 2) Modification of starting point  Conversion for units: 0.55 mg/L x 1000 = 550 mg/m3
Correction of rat inhalation NOAEC to rat oral NOAEL – correction for respiratory volume and for difference in absorption rates 

NOAELrat:159.5 mg/kg bw/day

(= 550 x 0.29 x 1)

Assumption: Based on ECHA guidance (Chapter R.8) no default factor was applied for differences in absorption in rats and humans and therefore absorption was assumed to be 100% via the oral and inhalation route
Step 3) Assessment factors  ECHA assessment factors used
Interspecies (allometric scaling) 4 (rat) 
Interspecies 2.5 (for systemic effects) 
Intraspecies 10 (for general population) 
Exposure duration 2 (for sub-chronic to chronic) 
Dose response
Quality of database
 Total Assessment Factors 200 
 General Population DNELlong-term for oral route -Systemic

0.8 mg/kg bw/day

(= 159.5 x 1/(4 x 2.5 x 10 x 2 x 1 x 1))