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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:

2.5 (interspecies - for systemic effects); 5 (intraspecies - for workers); 2 (exposure duration - subchronic to chronic)

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
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:
2.06 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:

4 (interspecies - allometric scaling (rat)); 2.5 (interspecies - for systemic effects); 5 (intraspecies - for workers); 2 (exposure duration - subchronic to chronic)

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:
DNEL (Derived No Effect Level)
Value:
1.53 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
other: EC3
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
10
AF for intraspecies differences:
1
AF for remaining uncertainties:
1

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Acute/Short-term exposure – Systemic effects:

 

1) Dermal DN(M)EL:

 

A DNEL for short term duration (short term event, peak exposure) will not need to be derived in the case where an acute toxicity hazard (leading to C&L) has not been identified.

 

2) Inhalation DN(M)EL:

 

High peak exposure is unlikely considering that propane-1 -thiol is highly malodorous. Therefore, a DNEL is not derived.

 

Acute/Short-term exposure – Local effects:

 

1) Dermal DN(M)EL:

 

The substance is classified for skin sensitisation therefore an acute dermal DNEL is derived from the read-across EC3 value.

 

2) Inhalation DN(M)EL:

 

High peak exposure is unlikely considering that propane-1 -thiol is highly malodorous. Therefore, a DNEL is not derived.

 

 

Long-term exposure – Systemic effects:

 

1) Dermal DN(M)EL:

The dermal DNEL has been derived based on read-across of a 90-day inhalation study with 2-methylpropane-2 -thiol (TBM).

Step 1) Relevant dose-descriptor

NOAEC6h/rat: 0.721 mg/L

Step 2) Modification of starting point

Conversion for units:

0.721 mg/L x 1000 = 721 mg/m3

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

NOAELrat: 274 mg/kg bw/day

(= 721 x 0.38 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

Correction of exposure duration in study

(6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/ week)

Corrected NOAEL = 205.5 mg/kg bw/day

(=274 x 6/8)

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

2.06 mg/kg bw/day

(= 205.5 x 1/(4 x 2.5 x 5 x 2 x 1 x 1))

2) Inhalation DN(M)EL:

The inhalation DNEL has been derived based on read-across of a 90-day inhalation study with 2-methylpropane-2 -thiol (TBM).

Step 1) Relevant dose-descriptor

NOAEC6h/rat: 0.721 mg/L
Step 2) Modification of starting point  Conversion for units:0.721 mg/L x 1000 = 721 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 = 362.3 mg/m3(= 721 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

14.5 mg/m3

(= 362.3 x 1/(2.5 x 5 x 2 x 1 x 1))

Long-term exposure – Local effects:

 

1) Dermal DN(M)EL:

No-threshold effect and/or no dose-response information available.

2) Inhalation DN(M)EL:

The inhalation DNEL has been derived based on read-across of a 90-day inhalation study with 2-methylpropane-2 -thiol (TBM).

Step 1) Relevant dose-descriptor

NOAEC6h/rat: 0.37 mg/L
Step 2) Modification of starting point  Conversion for units:0.37 mg/L x 1000 = 370 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 m3 
Step 3) Assessment factors ECHA assessment factors used 
 Interspecies 1 (for local effects) 
 Intraspecies 5 (for workers) 
 Exposure duration 2 (for sub-chronic to chronic) 
 Dose response
 Quality of database  1
 Total Assessment Factors 10 
Worker DNELlong-term for inhalation route -Local

18.6 mg/m3

(= 370 x 6/8 x 6.7/10 x 1/(1 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:
2.57 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Dose descriptor:
NOAEC
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:
0.74 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
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

Acute/Short-term exposure – Systemic effects:

 

1) Dermal DN(M)EL:

 

A DNEL for short term duration (short term event, peak exposure) will not need to be derived in the case where an acute toxicity hazard (leading to C&L) has not been identified.

 

2) Inhalation DN(M)EL:

 

Exposure is unlikely due to the highly malodorous nature of 2 -methylpropane-2-thiol. Therefore, a DNEL is not derived.

 

Acute/Short-term exposure – Local effects:

 

1) Dermal DN(M)EL:

 

There is no potential for dermal exposure of consumers therefore a DNEL is not derived.

 

2) Inhalation DN(M)EL:

 

Exposure is unlikely due to the highly malodorous nature of 2 -methylpropane-2-thiol. Therefore, a DNEL is not derived.

Long-term exposure – Systemic effects:

 

1) Dermal DN(M)EL:

No-threshold effect and/or no dose-response information available.

2) Inhalation DN(M)EL:

The inhalation DNEL has been derived based on read-across of a 90-day inhalation study with 2-methylpropane-2 -thiol (TBM).

Step 1) Relevant dose-descriptor

NOAEC6h/rat: 0.721 mg/L
Step 2) Modification of starting point  Conversion for units:0.721 mg/L x 1000 = 721 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 = 128.7 mg/m3(= 721 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

2.57 mg/m3

(= 128.7 x 1/(2.5 x 10 x 2 x 1 x 1))

3) Oral DN(M)EL:

 

The oral DNEL has been derived based on read-across of a 90-day inhalation study with 2-methylpropane-2 -thiol (TBM).

Step 1) Relevant dose-descriptor

 NOAEC6h/rat: 0.721 mg/L
Step 2) Modification of starting point  Conversion for units:0.721 mg/L x 1000 = 721 mg/m3
Correction of rat inhalation NOAEC to rat oral NOAEL – correction for respiratory volume and for difference in absorption rates 

NOAELrat: 829.15 mg/kg bw/day

(= 721 x 1.15 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
Correction of exposure duration in study (6 hrs/day, 5 days/week) to default general population exposure (24 hrs/day, 7 days/ week)Corrected NOAEL = 148.04 mg/kg bw/day(= 829.15 x 6/24 x 5/7)
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

0.74 mg/kg bw/day

(= 148.04 x 1/(4 x 2.5 x 10 x 2 x 1 x 1))

Long-term exposure – Local effects:

 

1) Dermal DN(M)EL:

No-threshold effect and/or no dose-response information available.

2) Inhalation DN(M)EL:

The inhalation DNEL has been derived based on read-across of a 90-day inhalation study with 2-methylpropane-2 -thiol (TBM).

Step 1) Relevant dose-descriptor

NOAEC6h/rat: 0.37 mg/L
Step 2) Modification of starting point  Conversion for units:0.37 mg/L x 1000 = 370 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)
Step 3) Assessment factors ECHA assessment factors used 
 Interspecies 1 (for local effects) 
 Intraspecies 10 (for general population) 
 Exposure duration 2 (for sub-chronic to chronic) 
 Dose response
 Quality of database 1
 Total Assessment Factors 20 
General PopulationDNELlong-term for inhalation route -Local

3.30 mg/m3

(= 370 x 6/24 x 5/7 x 1/(1 x 10 x 2 x 1 x 1))