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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
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
721 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
362.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

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 mg/m³ /10 m³ Corrected NOAEC = 362.3 mg/m³ (= 721 x 6/8 x 6.7/10)
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
Default systemic effects
AF for intraspecies differences:
5
Justification:
Default workers
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
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
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
Value:
370 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
For sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
Justification:
For local effects
AF for intraspecies differences:
5
Justification:
For workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEC
Value:
721 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
205.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

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 a reliable 90 -day inhalation study was available. 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)
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
For sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
For systemic effect
AF for intraspecies differences:
5
Justification:
For worker population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

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
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
Value:
721 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
128.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

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

NOAEC 6h/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)
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
For systemic effect
AF for intraspecies differences:
10
Justification:
For general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor:
NOAEC
Value:
370 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
For sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
Justification:
For local effects
AF for intraspecies differences:
10
Justification:
For general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
3 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
Dose descriptor starting point:
NOAEC
Value:
721 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
592 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A 90-day inhalation repeated dose toxicity study (Ulrich, 1982; Klimisch score = 2) has been performed and is used as the starting point for this DNEL. 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).

The following correction was made to the NOAEC (inhaled): Correction respiratory volume rat (24 hour) = 1.15 m³/kg bw. Correction for dosing frequency: 5 days/7 days. Therefore, the corrected NOAEL for repeat-dose systemic effects via the dermal/oral route is: 721*1.15*(5/7) = 592 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default, subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default, general population
AF for the quality of the whole database:
1
Justification:
Default, the NOAEL is from a reliable study on 2-methylpropane-2-thiol.
AF for remaining uncertainties:
1
Justification:
Default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
83.3 µg/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:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A 28-day oral repeated dose toxicity study (MHLW, 2006; Klimisch score = 1) of 2-methylpropane-2-thiol has been performed and is used in the derivation of this DNEL. The NOAEL used was 50 mg/kg bw/day. No modification of the dose descriptor starting point is required.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default, subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default, Rat to human
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default, general population
AF for the quality of the whole database:
1
Justification:
Default, the NOAEL is from a reliable study on 2-methylpropane-2-thiol.
AF for remaining uncertainties:
1
Justification:
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