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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:
14.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
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:
exposure based waiving
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
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

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 2 -methylpropane-2-thiol is highly malodorous. Therefore, a DNEL is not derived.

 

Acute/Short-term exposure – Local 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 2 -methylpropane-2-thiol is highly malodorous. Therefore, a DNEL is not derived.

 

 

Long-term exposure – Systemic effects:

 

1) Dermal DN(M)EL:

No key dermal repeat dose toxicity data was available for 2 -methylpropane-2-thiol. One key oral 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 data could not be verified without the study report. Therefore, in the absence of oral data, key inhalation data (Ulrich, 1982; Klimisch score = 2) was used by performing a route-to-route extrapolation. The NOAEC used was 0.721 mg/L (196 ppm or 721 mg/m3).

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:

One key study (Ulrich, 1982; Klimisch score = 2) was available for 2 -methylpropane-2-thiol. In this 90 -day inhalation study, the repeated dose toxicity of 2 -methylpropane-2-thiol was investigated in Sprague-Dawley rats.The NOAEC was identified to be 0.721 mg/L (196 ppm or 721 mg/m3) based on the absence of systemic toxicity effects at the highest concentration tested (0.721 mg/L or 196 ppm).

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:

One key read across study (Kim et al., 2009; Klimisch score = 1) was available for butane-2-thiol, a structural analog of 2 -methylpropane-2-thiol. In this 13 week inhalation study, the repeated dose toxicity of butane-2-thiol was investigated in Sprague-Dawley rats.The NOAEC was identified to be 0.37 mg/L (100 ppm) based on effects occurring at the next highest concentration of 1.48 mg/L (400 ppm). 

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:
exposure based waiving
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:
exposure based waiving
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving

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:
exposure based waiving
DNEL related information

General Population - Hazard for the eyes

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:

 

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.

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:

One key study (Ulrich, 1982; Klimisch score = 2) was available for 2 -methylpropane-2-thiol. In this 90-day inhalation study, the repeated dose toxicity of 2 -methylpropane-2-thiol was investigated in Sprague-Dawley rats.The NOAEC was identified to be 0.721 mg/L (196 ppm or 721 mg/m3) based on the absence of systemic toxicity effects at the highest concentration tested (0.721 mg/L or 196 ppm).

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:

 

One key study (MHLW, 2006; Klimisch score = 1) of 2-methylpropane-2-thiol has been performed but not used in the derivation of this DNEL because the data could not be verified without a study report. Therefore in the absence of oral data, inhalation data (Ulrich, 1982; Klimisch score = 2) from 2 -methylpropane-2-thiol was used by performing a route-to-route extrapolation. The NOAEC used was 0.721 mg/L.

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:

One key read across study (Kim et al., 2009; Klimisch score = 1) was available for butane-2-thiol, a structural analog of 2 -methylpropane-2 -thiol. In this 13 week inhalation study, the repeated dose toxicity of butane-2-thiol was investigated in Sprague-Dawley rats.The NOAEC was identified to be 0.37 mg/L (100 ppm) based on effects occurring at the next highest concentration of 1.48 mg/L (400 ppm).

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))