2-methylbutan-2-ol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

17.2 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):

75

Modified dose descriptor starting point:

NOAEC

Value:

1 287 mg/m³

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

267.8 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

Dose descriptor:

NOAEC

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

1

Justification:

Since the respiratory irritation is dependent only on concentration no assessment factor for time extrapolation is used.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required.

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.5 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):

300

Modified dose descriptor starting point:

other: NOAELcorr

Value:

743 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A dermal toxicity study (Rowe and McCollister, 1982) with repeated exposure was conducted with rabbits. However, the documentation is unsufficient for assessment and the study is classified to be not assignable (class 4 according to Klimisch et al., 1996). Since no reliable data on repeated dermal exposure are available data on repeated inhalation exposure were taken into acount.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Worker - Hazard via dermal route

Long-term exposure - systemic effects

A dermal toxicity study (Rowe and McCollister, 1982) with repeated dermal exposure (28 days) was conducted with rabbits. In this study only two dose levels with the large spacing factor of 10 were used. Systemic toxicity was seen at the high, but not at the low dose level. Due to the large dose spacing a reliable NOAEL can not be derived. Moreover, there is only a brief abstract of the study available (yielding in the Klimisch score 4). In the absence of a reliable dermal toxicity study with repeated exposure, the worker-DNEL long-term for dermal route - systemic was derived from the NOAEC obtained in the key subacute inhalation repeated dose study in Wistar rats. A corrected dermal NOAEL (NOAELcorr) was calculated using the default respiratory volume reflecting the daily exposure period of the rats during the study (6 hours). The same absorption rate was assumed for the inhalation (rat) and dermal route (human) following a conservatve approach.

 

Calculation of the NOAELcorr

- Standard dose descriptor (NOAEC): 2561 mg/m³

- Standard respiratory volume of the rat (sRVrat) for 6 hours: 0.29 m³/kg bw/d

- Inhalation absorption of the rat/dermal absorption of humans (ABSinhal-rat)/ABSdermal-human): 1/1

Corrected dermal NOAEL for workers:

= NOAEC * (sRVrat) * (ABSinhal-rat/ABSdermal-human)

= 2561 mg/m³ * (0.29 m³/kg bw/d)* (1/1)

= 743 mg/kg bw/d

 

References

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.Version: 2.1, ECHA-2012 -G-19 -EN.

ECHA (2012). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation.Version: 2.0, ECHA-2012 -G-16 -EN.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.3 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):

150

Modified dose descriptor starting point:

NOAEC

Value:

640 mg/m³

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

10

Justification:

The default value for the group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

66.6 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor:

NOAEC

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

1

Justification:

Since the respiratory irritation is dependent only on concentration no assessment factor for time extrapolation is used.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

10

Justification:

The default value for the group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required.

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.24 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):

600

Modified dose descriptor starting point:

other: NOAELcorr

Value:

743 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A dermal toxicity study (DOW Chemical Company, 1982) with repeated exposure was conducted with rabbits. However, the documentation is unsufficient for assessment and the study is classified to be not assignable (class 4 according to Klimisch et al., 1996). Since no reliable data on repeated dermal exposure are available data on repeated inhalation exposure were taken into acount.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

10

Justification:

The default value for the group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.24 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):

600

Modified dose descriptor starting point:

other: NOAELcorr

Value:

743 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data available on repeated exposure by the oral route.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

10

Justification:

The default value for the group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

General Population - Hazard via dermal route

Long-term exposure - systemic effects

A dermal toxicity study (Rowe and McCollister, 1982) with repeated dermal exposure (28 days) was conducted with rabbits. In this study only two dose levels with the large spacing factor of 10 were used. Systemic toxicity was seen at the high, but not at the low dose level. Due to the large dose spacing a reliable NOAEL can not be derived. Moreover, there is only a brief abstract of the study available (yielding in the Klimisch score 4). In the absence of a reliable dermal toxicity study with repeated exposure, the general population-DNEL long-term for dermal route - systemic was derived from the NOAEC obtained in the key subacute inhalation repeated dose study in Wistar rats. A corrected dermal NOAEL (NOAELcorr) was calculated using the default respiratory volume reflecting the daily exposure period of the rats during the study (6 hours).The same absorption rate was assumed for the inhalation (rat) and dermal route (human) following a conservative approach.

 

Calculation of the NOAELcorr

- Standard dose descriptor (NOAEC): 2561 mg/m³

- Standard respiratory volume of the rat (sRVrat) for 6 hours: 0.29 m³/kg bw/d

- Inhalation absorption of the rat/dermal absorption of humans (ABSinhal-rat)/ABSdermal-human): 1/1

Corrected dermal NOAEL for general population:

= NOAEC * (sRVrat) * (ABSinhal-rat/ABSdermal-human)

= 2561 mg/m³ * (0.29 m³/kg bw/d)* (1/1)

= 743 mg/kg bw/d

 

 

General population - Hazard via oral route

Since for the oral route the similar situation as for the dermal route applies, the corrected oral NOAEL is identical with the corrected dermal NOAEL.

References

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.Version: 2.1, ECHA-2012 -G-19 -EN.

ECHA (2012). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation.Version: 2.0, ECHA-2012 -G-16 -EN.