Aluminium tri-sec-butanolate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

161 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

65.625

Dose descriptor starting point:

NOAEC

Value:

10 600 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

10 600 mg/m³

Explanation for the modification of the dose descriptor starting point:

Based on NOAEC from inhalation teratology study (Nelson 1989).

Exposure duration in this study is 7 hours/day. Therefore an additional factor of 7/8 is included to reflect the difference of exposure duration between the study and workers.

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

NOAEC from subactute study

AF for interspecies differences (allometric scaling):

1

Justification:

not required

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

for worker, a default AF of 5 is to be used

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

0.875

Justification:

accounts for the difference in exposure duration

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)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

300 mg/kg bw/day

Most sensitive endpoint:

effect on fertility

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEL

Value:

1 500 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

15 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Based on NOAEL from oral 2-Gen.Reproductive Toxicity Study 1500 mg/kg bw/d * 100/10 (correction for 10% dermal absorption versus 100 % oral) = 15000 mg/kg bw/d

AF for dose response relationship:

1

Justification:

DNEL based on corrected NOAEL

AF for differences in duration of exposure:

1

Justification:

NOAEL from chronic study

AF for interspecies differences (allometric scaling):

4

Justification:

rats were used in the study

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

for worker, a default AF of 5 is to be used.

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not 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:

low hazard (no threshold derived)

Additional information - workers

As aluminium tri-sec-butylate hydrolyses immediately upon contact with water or moisture to aluminium hydroxide and sec-butanol, the toxicokinetic behaviour is determined by these decomposition products and their absorption, distribution metabolism and excretion. Thus, in the TK-assessment, the focus lies on sec-butanol and aluminium 3+ compounds. As bioavailability (absorption) of aluminium compounds is limited (typically less than 1%) but sec-butanol is well absorbed the effects of sec-butanol do determine DNEL and PNEC derivation.

Acute DNELs:

Worker: Production of aluminium tri-sec-butylate is in excess of 10 t/y. According to the REACH "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishment of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on repeated dose toxicity is normally sufficient to ensure that adverse effects do not occur. Thus, as long term DNELs are available for sec-butanol and sec-butanol is not classified for acute toxicity via any route of exposure, separate acute DNELs were not derived. Since there are only few and partially only conditionally convincing results concerning the irritant effect of 2-butanol in man and animal, any irritant effect is considered unlikely at this concentration.

Long-term DNELs:

There is no OEL value for sec-butanol or aluminium tri-sec-butylate at community level.. 

Hence, the systemic DNELs for long term inhalation and dermal exposure were based on the inhalation teratogenicity study and the 2-generation oral (drinking water application) reproductive toxicity study with sec-butanol. Considering the bioavailability of 2-butanol compared with aluminium compounds, both resulting from hyrolysis of aluminium tri-sec-butylate, this is considered a conservative approach.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

242 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

43.75

Dose descriptor starting point:

NOAEC

Value:

10 600 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

10 600 mg/m³

Explanation for the modification of the dose descriptor starting point:

Based on NOAEC from inhalation teratology study (Nelson 1989).

Exposure duration in this study is 7 hours/day. Therefore an additional factor of 7/24 is included to reflect the difference of exposure duration between the study and workers.

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

subacute study

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable for inhalation route

AF for other interspecies differences:

2.5

Justification:

default factor

AF for intraspecies differences:

10

Justification:

consumer exposure

AF for the quality of the whole database:

1

AF for remaining uncertainties:

0.29

Justification:

7/24

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)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

150 mg/kg bw/day

Most sensitive endpoint:

effect on fertility

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEL

Value:

1 500 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

15 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Based on NOAEL from oral 2-Gen.Reproductive Toxicity Study 1500 mg/kg bw/d * 100/10 (correction for 10% dermal absorption versus 100 % oral) = 15000 mg/kg bw/d

AF for dose response relationship:

1

Justification:

based on modified NOAEL

AF for differences in duration of exposure:

1

Justification:

based on chronic study

AF for interspecies differences (allometric scaling):

4

Justification:

study in rat

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

10

Justification:

consumer exposure

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not 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:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)