Aluminium tri-sec-butanolate

Endpoint summary

Description of key information

Upon contact with water or moisture (e.g. within mucous membranes) aluminium tri-sec-butanolate hydrolyses immediately to butan-2-ol and aluminium 3+ cations (as hydroxide and oxyhydroxide). Hence, toxicity is determined by the toxicity of these two species.

The acute oral toxicity of butan-2-ol in rat as expressed as LD50 is 2193 mg/kg bw (Price 1986). For aluminium nitrate and aluminium tri-isopropanolate oral LD50 values of 4280 mg/kg and 11300 mg/kg bw are reported (Smyth 1969).

For acute inhalation toxicity no LC50 could be derived for butan-2-ol and a LC50 of 888 mg/m3 for aluminium flakes were derived (Reynolds 1986).

The dermal LD50 for butan-2-ol in rats is >2000 mg/kg bw (Price 1986).

Butan-2-ol showed local irritant effects on the respiratory system and transient effects on the CNS (drowsiness and dizziness) and is therefore classified as STOT SE 3, H335/H336 (according to Annex VI of Regulation EC 1272/2008).

Aluminium species (hydroxide or oxide) that may be formed during hydrolysis are not classified for acute toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

-reliability scoring was based on 2001 guideline

Deviations:

yes

Remarks:

-insignificant deviation, guideline suggests using animals of all the same sex; no necropsy conducted

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Ltd.
- Age at study initiation: 9 to 11 weeks old
- Weight at study initiation: Weight on Day 1 = 189 to 219 g (males) and 125 to 149 g (females)
- Fasting period before study: Fasted overnight (18 h) prior to dosing.
- Housing: Two days before dosing, the rats to be used were housed in groups of 2 or 3 animals of the same sex per cage.
- Diet (e.g. ad libitum): Food (PRD, Labsure Animal Foods, Dorset), ad libitum
- Water (e.g. ad libitum): Filtered but untreated water from the public supply, ad libitum
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): air temperature was 19 to 25 °C
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: not reported

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Range finding studies were performed.

Doses:

950, 1200, 1500, 2000, and 2400 mg/kg bw

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed for clinical signs over 14 days. Body weight measurements were recorded on Days 1, 7, and 14.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Statistics:

Acute oral LD50 values were calculated using probit analysis (Finney, 1977).

Sex:

male

Dose descriptor:

LD50

Effect level:

2 054 mg/kg bw

Remarks on result:

other: 95% fiducial limits were 1283 - 4018 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

2 328 mg/kg bw

Remarks on result:

other: 95% fiducial limits were 1470 - 5428 mg/kg bw

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 193 mg/kg bw

Remarks on result:

other: 95% fiducial limits were 1608 - 4146 mg/kg bw

Mortality:

Over the 14-day observation period, 0, 1, 2, 1, and 8 animals died in the 950, 1200, 1500, 2000, and 2400 mg/kg bw dose groups, respectively. For more details, refer to Table 1 (attached).

Clinical signs:

other: All rats at all dose levels had gait and/or posture abnormalities. In the higher dose groups some rats were comatose or prostrate within a few hours of dosing, with some animals being unconscious for 24 hours or more. Some rats in the top dose group (2400

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (male/female rat) was determined being 2193 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 193 mg/kg bw

Quality of whole database:

Based on the available study on the hydrolysis product butan-2-ol

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

In the available study on the most volatile hydrolysis product butan-2-ol no value for LC50 could be derived.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guidelines.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

-reliability scoring based on 1987 guideline

Deviations:

yes

Remarks:

-insignificant deviation, guideline suggests using animals of all the same sex

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Ltd.
- Age at study initiation: 9 to 11 weeks old
- Weight at study initiation: Weight on Day 1 = 227 to 265 g (males) and 153 to 170 g (females)
- Fasting period before study: Fasted overnight (18 h) prior to dosing.
- Housing: Two days before dosing, the rats to be used were housed in groups of 2 or 3 animals of the same sex per cage.
- Diet (e.g. ad libitum): Food (PRD, Labsure Animal Foods, Dorset), ad libitum; however, food was withheld 24 hours after administration
- Water (e.g. ad libitum): Filtered but untreated water from the public supply, ad libitum
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): air temperature was 19 to 25 °C
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal
- % coverage: not reported
- Type of wrap if used: The test material was covered with a piece of aluminum foil which was held in place by a double over-wrap of waterproof adhesive tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the tape and foil were carefully removed and the skin was washed with warm dilute detergent solution and then dried.
- Time after start of exposure: 24 hrs


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not reported
- Concentration (if solution): undiluted
- Constant volume or concentration used: not applicable
- For solids, paste formed: not applicable

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals/sex

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for signs of toxicity for 14 days after dosing. Body weights were recorded on Days 1, 7, and 14.
- Necropsy of survivors performed: No
- Other examinations performed: clinical signs and body weight

Statistics:

Statistical analysis was not performed, but is not required.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: The LD50 value was not determined since none of the rats died at a dose level of 2000 mg/kg bw. The LD50 value was predicted to be greater than 2000 mg/kg bw.

Mortality:

None of the rats died over a period of 14 days.

Clinical signs:

other: There were no clinical signs seen.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (dermal, rat) >2000 mg/kg bw

Executive summary:

The acute (24 h) percutaneous LD50 of the undiluted test material in rats was greater than 2000 mg/kg bw. None of the rats died during the 14 day observation period following dermal exposure to 2000 mg/kg bw 2 -butanol.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Aluminium hydroxide, aluminium oxide, aluminium oxyhydroxide are insoluble in water. Due to their insolubility it can be assumed that the absorption of these aluminium compounds via the skin will be limited. Therefore the LD50 is based on the other hydrolysis product butan-2-ol

Additional information

Upon contact with water or moisture (e.g. within mucous membranes) aluminium tri-sec-butanolate hydrolyses immediately to butan-2-ol and aluminium 3+ cations (as hydroxide and oxyhydroxide). Hence, toxicity is determined by the toxicity of these two species.

Justification for classification or non-classification

Upon contact with water or moisture (e.g. within mucous membranes) aluminium tri-sec-butanolate hydrolyses immediately to butan-2-ol and aluminium 3+ cations (as hydroxide and oxyhydroxide). Hence, toxicity is determined by the toxicity of these two species. Aluminium species are not classified for acute toxicity, but butan-2-ol is classified as STOT SE 3, H335/H336 (according to Annex VI of Regulation EC 1272/2008). Therefore aluminium tri-sec-butanolate will be classified as H335 and H336 in a worst case approach.