2-propanol and 2-butanol production, distn. residues

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

228.1 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:

11 350 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

5 703 mg/m³

Explanation for the modification of the dose descriptor starting point:

A NOAEC of 11350 mg/m³, resulting from a 90d inhalation exposure repeated dose toxicity study was considered for the derivation of the DNEL. This NOAEC was corrected for DNEL derivation by considering difference in daily exposure (6 h/d in study, 8 h/d for workers) and considering differences in respiratory volume between rats as used in study and workers performing lightweight activities in line with ECHA guidance for derivation of DNELs.

NOAEC of 11350 mg/m³ * (6 h/d / 8 h/d) *(6.7 m³ (8h)/10 m³ (8h)) = 5’703 mg/m³ (corrected NOAEC)

AF for dose response relationship:

1

Justification:

dose descriptor is a NOAEC from reliable study

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic assessment factor

AF for interspecies differences (allometric scaling):

1

Justification:

rat - systemic effect (inhalation route) - not applicable for setting inhalation DNEL

AF for other interspecies differences:

2.5

Justification:

systemic effect remaining differences according to guidance

AF for intraspecies differences:

5

Justification:

workers default according to guidance

AF for the quality of the whole database:

1

Justification:

good quality, subchronic data, supported by read-across reproductive data

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:

no hazard identified

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:

31.35 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:

11 350 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

3 235 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A NOAEC of 11350 mg/m³, resulting from a 90d inhalation exposure repeated dose toxicity study was considered for the derivation of the DNELdermal for workers. This NOAEC was corrected for DNEL derivation by considering difference in daily exposure (6 h/d in study, 8 h/d for workers) and considering conversion from NOAEC to NOAEL by multiplying with 0.38 m³/kg bw in line with ECHA guidance for derivation of DNELs.

NOAEC of 11350 mg/m³ * (6 h/d / 8 h/d) *(0.38 m³/kg bw) = 3’235 mg/m³ (corrected NOAEL dermal)

AF for dose response relationship:

1

Justification:

dose descriptor is a NOAEL

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat - systemic effect (dermal route)

AF for other interspecies differences:

2.5

Justification:

systemic effect

AF for intraspecies differences:

5

Justification:

workers

AF for the quality of the whole database:

1

Justification:

good quality

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:

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:

low hazard (no threshold derived)

Additional information - workers

As “2-propanol and 2-butanol production, distn. residues” is not classified for acute toxicity, acute DNEL values do not have to be derived according to the REACH "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health". As the substance also did not show local effects (inhalation), no DNEL value had to be derived for local effects either.

As no information on dose-response for eye irritation and skin irritation is available, no DNEL was derived for these endpoints; the substance is classified for skin irritation (category 2) conservatively and for eye irritation (category 2) based on weak response in studies and thus considered of low hazard, without deriving a threshold. However, a qualitative approach to assessing and controlling the risks was followed.

For long-term effects, the toxicity to reproduction studies assessed for read-across substance are in line with the results seen in a sub-chronic inhalation toxicity study on the substance itself, supporting the NOAEC seen in this study of 11’350 mg/m³ to be chosen as basis for DNEL derivation for long term systemic toxicity. Corresponding DNELs were derived following the methodology as described in Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, November 2012.

In lack of detailed information on absorption rates and assuming similar absorption rates by inhalation, dermal and oral exposure, no correction for absorption via routes of exposure was applied.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

56.75 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:

11 350 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

2 838 mg/m³

Explanation for the modification of the dose descriptor starting point:

A NOAEC of 11350 mg/m³, resulting from a 90d inhalation exposure repeated dose toxicity study was considered for the derivation of the DNEL. This NOAEC was corrected for DNEL derivation by considering difference in daily exposure (6 h/d in study, 24 h/d for general population) in line with ECHA guidance for derivation of DNELs.

NOAEC of 11350 mg/m³ * (6 h/d / 24 h/d) = 2’838 mg/m³ (corrected NOAEC)

AF for dose response relationship:

1

Justification:

dose descriptor is a NOAEL

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

rat - systemic effect (inhalation route)

AF for other interspecies differences:

2.5

Justification:

systemic effect

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

good quality

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:

no hazard identified

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:

16.32 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:

11 350 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

3 263 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A NOAEC of 11350 mg/m³, resulting from a 90d inhalation exposure repeated dose toxicity study was considered for the derivation of the DNELdermal for workers. This NOAEC was corrected for DNEL derivation by considering difference in daily exposure (6 h/d in study, 24 h/d for general population) and considering conversion from NOAEC to NOAEL by multiplying with 1.15 m³/kg bw in line with ECHA guidance for derivation of DNELs.

NOAEC of 11350 mg/m³ * (6 h/d / 24 h/d) * (1.15 m³/kg bw) = 3’263 mg/m³ (corrected NOAEL dermal)

AF for dose response relationship:

1

Justification:

dose descriptor is a NOAEL

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat - systemic effect (dermal route)

AF for other interspecies differences:

2.5

Justification:

systemic effect

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

good quality

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:

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:

16.32 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:

13 053 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

3 263 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A NOAEC of 11350 mg/m³, resulting from a 90d inhalation exposure repeated dose toxicity study was considered for the derivation of the DNELdermal for workers. This NOAEC was corrected for DNEL derivation by considering difference in daily exposure (6 h/d in study, 24 h/d for general population) and considering conversion from NOAEC to NOAEL by multiplying with 1.15 m³/kg bw in line with ECHA guidance for derivation of DNELs.

NOAEC of 11350 mg/m³ * (1.15 m³/kg bw) = 13053 mg/kg bw/d converted NOAEL (from NOAEC)

13053 mg/kg bw * (6 h/d / 24 h/d) = 3’263 mg/m³ (corrected NOAEL oral)

AF for dose response relationship:

1

Justification:

dose descriptor is a NOAEL

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat - systemic effect (oral route)

AF for other interspecies differences:

2.5

Justification:

systemic effect

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

good quality

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

As “2-propanol and 2-butanol production, distn. residues” is not classified for acute toxicity, acute DNEL values do not have to be derived according to the REACH "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health". As the substance also did not show local effects (inhalation), no DNEL value had to be derived for local effects either.

As no information on dose-response for eye irritation and skin irritation is available, no DNEL was derived for these endpoints; the substance is classified for skin irritation (category 2) conservatively and for eye irritation (category 2) based on weak response in studies and thus considered of low hazard, without deriving a threshold. However, a qualitative approach to assessing and controlling the risks was followed.

For long-term effects, the toxicity to reproduction studies assessed for read-across substance are in line with the results seen in a sub-chronic inhalation toxicity study on the substance itself, supporting the NOAEC seen in this study of 11’350 mg/m³ to be chosen as basis for DNEL derivation for long term systemic toxicity. Corresponding DNELs were derived following the methodology as described in Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, November 2012.

In lack of detailed information on absorption rates and assuming similar absorption rates by inhalation, dermal and oral exposure, no correction for absorption via routes of exposure was applied.