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.

Butan-2-ol was tested for skin and eye irritation in the rabbit (Price 1986). The substance was not irritating to the skin, but irritating to the eyes (cat 2).

Results from Lansdown (1973), a non-guideline study, indicate that repeated exposure (5 daily administrations) of a 10% aluminium hydroxide suspension did not lead to dermal irritation under the experimental conditions in mice, rabbits and pigs. Macroscopic (erythema, thickening and scaling), microscopic pathological (stained thin-sections) and histochemical examinations were carried out. No accumulation of aluminium was observed in the epidermis after application of aluminium hydroxide.

Application of 0.5 mg Aluminium nitrate to the rabbit skin during 24 hours under occlusion showed some slight irritation, not sufficient for classification as irritant (Guillot 1982). Aluminium nitrate was, however shown to be a severe eye irritant in rabbits (Guillot 1982).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

under occlusion

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rouché SA, Couhé, France
- Weight at study initiation: 2.5 kg
- Housing: no data
- Diet/ water: no data

ENVIRONMENTAL CONDITIONS: no data

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

not specified

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hour (test includes a protocol with 24 hour exposure, but this is not taken into consideration)

Observation period:

upto 14 days (on day 1, 2, 3, 4, 7 and 14)

Number of animals:

6 males/treatment

Details on study design:

TEST SITE
- Area of exposure: 4-6 cm2 (gauge pad moistened with water was applied to the test site)
- Type of wrap if used: occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : after 1, 24, 48 and 72 hours and on day 7 and 14

SCORING SYSTEM:
- Method of calculation: PCI (not further specified)
- Protocols were based on OECD, AFNOR and Cosmetic regulations, which all have slightly different scoring systems

Irritation parameter:

overall irritation score

Basis:

mean

Remarks on result:

no indication of irritation

Remarks:

based on OECD and AFNOR protocols

Irritant / corrosive response data:

The PCI was 0.36 and 0.35 for AFNOR and OECD protocols. No details provided.
For the cosmetic protocol with an exposure time of 24 hours under occlusion the substance was found slightly irritating (PCI 0.54)

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not irritating to the skin

Reference 2

Endpoint:

skin irritation: in vivo

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:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

-reliability scoring based on 2002 guideline

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sittingbourne Research Centre breeding colony
- Age at study initiation: 4 to 9 months old
- Weight at study initiation: 4440 to 4940 g (males) and 4100 to 4982 g (females)
- Housing: Housed individually
- Diet (e.g. ad libitum): Food (standard rabbit diet, S.Q.C., Special Diet Services Ltd., Essex), ad libitum
- Water (e.g. ad libitum): Filtered but untreated water from the public supply (whether or not water was administered ad libitum was not reported).
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 19 °C
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

other: dorsal hair between the shoulders and hindquarters was closely shorn

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3 animals/sex

Details on study design:

TEST SITE
- Area of exposure: dorsal hair between the shoulders and hindquarters
- % coverage: 2 cm x 2 cm
- Type of wrap if used: The patch and surrounding skin was covered by a single layer of gauze and held in place by means of an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treated skin was not washed.
- Time after start of exposure: After 4 hours, the wrapping and patch were removed.

SCORING SYSTEM: The test site was examined and scored for erythema and oedema on a graded scale of 0 to 4 using the criteria given below. Observations were made at 30 minutes after the removal of the patch (i.e. approximately 4 hours after application) and at 24, 48, and 72 hours, and 7 days after application. The mean score of each rabbit at each observation time and the group mean 24, 48, and 72 hours were calculated.

Erythema scale:
No erythema 0
Very slight erythema (perceptible, area not defined) 1
Well defined erythema (pale red, area well defined) 2
Moderate to severe erythema (bright red, area well defined) 3
Severe erythema (beet or crimson red) 4

Oedema scale:
No oedema 0
Very slight oedema (perceptible, edges of area not defined) 1
Slight oedema (edges of area defined by raising) 2
Moderate oedema (area well defined, raised I mm) 3
Severe oedema (area raised more than 1 mm, extends beyond exposure area) 4

Injury in depth:
Escharosis, necrosis 8
A score of 8 is equivalent to scoring 4 for erythema and 4 for oedema.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 4 h, 24h, 48h, 72 h, and 7 days

Score:

0

Max. score:

4

Remarks on result:

other: All individual scores were 0 at all time-points indicated.

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 4 h, 24h, 48h, 72 h, and 7 days

Score:

0

Max. score:

4

Remarks on result:

other: All individual scores were 0 at all time-points indicated.

Irritant / corrosive response data:

There were no skin reactions following the application of undiluted secondary butyl alcohol to rabbit skin for 4 hours. The test material is therefore not a skin irritant in rabbits.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this test sec-butanol was found being non-irritant to rabbit skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

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:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

-reliability scoring based on 2002 guideline

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Sittingbourne Research Centre breeding colony
- Age at study initiation: 4 to 9 months old
- Weight at study initiation: 3850 to 4292 g (males) and 4775 to 4920 g (females)
- Housing: Housed individually
- Diet (e.g. ad libitum): Food (standard rabbit diet, S.Q.C., Special Diet Services Ltd., Essex), ad libitum
- Water (e.g. ad libitum): Filtered but untreated water from the public supply (whether or not water was administered ad libitum was not reported).
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 19 °C
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3 animals/sex

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were not washed.
- Time after start of exposure: Not applicable.


SCORING SYSTEM: Same scale as the one provided in the OECD guideline, with the exception of 1 criteria (changes related to discharge were included in addition to the other parameters evaluated).

Discharge:
No discharge = 0
Any amount different from normal = 1
Discharge with moistening of lids and hairs adjacent to lids = 2
Discharge with moistening of llds and hairs and considerable area around eye = 3

The degree of irritation was classified using the following scheme which is based on the OECD Data Interpretation Guides (1984).

- No irritation - Exposure of the eye to the material under the specified conditions causes no significant ocular changes. No tissue staining with fluorescein is observed. Any changes that occur, clear within twenty-four hours.

- Irritation - Exposure of the eye to the material under the specified conditions causes minor, superficial, and transient changes of the cornea, iris, or conjunctiva as determined by external or silt-lamp examination with fluorescein staining. The appearance at any grading interval of any of the following changes is sufficient to characterize a response as irritation: opacity of the cornea (other than a slight dulling of the normal luster), hyperemia of the iris, or swelling of the conjunctivae. Any changes that are seen clear within seven days.

- Substantial irritation - Exposure of the eye to the material under the specified conditions causes significant injury to the eye, such as loss of the corneal epithelium, corneal opacity, iris (other than a slight injection), conjunctivitis, pannus, or bullae. The effects heal or clear within twenty-one days.

- Corrosion - Exposure of the eye to the material under the specified conditions results in significant tissue destruction (necrosis). Injuries persist or are expected to persist for twenty-one days or more.

The above classification is based on the most severe responses which are seen in any one animal of a treated group receiving the same test substance and treatment.

TOOL USED TO ASSESS SCORE: One drop of 2% fluorescein solution

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, and 72 hours

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: See attached table for individual results

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, and 72 hrs

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Remarks on result:

other: See attached table for individual results

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, and 72 hrs

Score:

0.2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: See attached table for individual results

Irritation parameter:

other: redness

Basis:

mean

Time point:

other: 24, 48, and 72 hrs

Score:

1.5

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: See attached table for individual results

Irritant / corrosive response data:

The instillation of undiluted secondary butyl alcohol into the conJunctival sac of one eye of each of six rabbits resulted in moderate initial pain. All rabbits had moderate conjunctival inflammation with some discharge, within 1 h of dosing. The swelling and discharge had largely cleared by 4 hours but the redness persisted in three rabbits at 7 days. These animals and one other animal had impaired iritic response and/or slight corneal opacity between 24 and 72 hours post-dosing. The effects had cleared by 7 days in all rabbits except for 1 animal. As this animal’s eye was intensely opaque over the entire cornea and there was no iritic response it was killed for humane reasons; recovery was not considered possible. The remaining rabbits were retained, and by 14 days, all ocular effects had cleared. Considering the fact that in 5/6 animals only mild, reversible, irritation (insufficient to classify) was observed, it seems to be an idiosyncratic animal. It is unclear from this study whether the lack of reversibility is directly related to the test material.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

2-Butanol was found to be irritating to eyes in this test.

Executive summary:

Under the conditions of this test 2 -butanol was found to be irritating to eyes, mainly due to formation of redness. All effects were fully reversible, with the excetion of one animal and the substance is considered irritating to eyes, Category 2 according to CLP (Regulation EC No 1272/2008).

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Rouché SA, Couhé, France
- Weight at study initiation: 2.5 kg
- Housing: no data
- Diet/ water: no data

ENVIRONMENTAL CONDITIONS: no data

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

100 mg

Observation period (in vivo):

at 1, 24, 48, 72, 96 h and 7 days after instillation

Number of animals or in vitro replicates:

6 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): additional test with washing after 4 and 30 seconds

SCORING SYSTEM: occular irritation index (Kay & Calandra)

TOOL USED TO ASSESS SCORE: no data

Irritation parameter:

overall irritation score

Basis:

mean

Score:

58.7 - 60.5

Remarks on result:

positive indication of irritation

Remarks:

extreme irritant

Irritation parameter:

overall irritation score

Basis:

mean

Score:

16.8

Remarks on result:

positive indication of irritation

Remarks:

severely irritant (rinse after 30 sec)

Irritation parameter:

overall irritation score

Basis:

mean

Score:

1.8

Remarks on result:

positive indication of irritation

Remarks:

irritatnt (rinse after 4 sec)

Irritant / corrosive response data:

The pH of a saturated solution of the substance was 0.8

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The substance is a severe eye irritant

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

It cannot be excluded that the results for the irritant properties as derived from the studies on aluminium nitrate are not representative for the aluminium species formed due to hydrolysis of aluminium tri-sec-butanolate. As the studies with the other hydrolysis product butan-2-ol lead to classification as an eye irritant (H319) and the harmonised classification for butan-2-ol includes classification as eye irritant (H319), these outcomes confirm the classification of aluminium tri-sec-butanolate as an eye irritant in a worst case approach.

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.

Butan-2-ol and Aluminium 3+ species are considered not irritant to the skin, but butan-1-ol is an eye irritant. Therefore aluminium tri-sec-butanolate needs to be classified as eye irritant according to Regulation EC 1272/2008 (H319).