2-methylpropane-2-thiol

Toxicological Summary

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

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