Aluminium triisopropanolate

Endpoint summary

Description of key information

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

The oral acute toxicity of aluminium tri-isopropanolate reported as LD50 was found to be 11.3 g/kg bw (Smyth 1969).

The acute oral toxicity has of isopropanol has been determined being LD50 (rat) = 5.84 g/kg bw, (Smyth 1948). No data for aluminium are available.

Inhalation exposure of male and female rats to 5000 and 10000 ppm isopropanol produces transient concentration-related narcosis and/or central nervous system sedation (Gill 1991). However, as no mortality was observed at the highest tested dose of 10000 ppm the LC50 was set to > 10000 ppm. The inhalation LC50 for aluminium flakes was 888 mg/m3 (Korsak 1994, Reynolds 1986).

Isopropanol has a very low acute dermal toxicity that has been determined being LD50 (dermal, rat) = 16.4 ml/kg bw = 12880 mg/kg bw.
Aluminium species (hydroxide or oxide) that may be formed during hydrolysis are not classified for acute toxicity. These species are insoluble in water and thus absorption via the skin is expected to be low (see also Flarend (2001)).

In several inhalation studies (not reported here) isopropanol showed transient effects on the CNS (drowsiness and dizziness) and is therefore classified as STOT SE 3, 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:

key study

Study period:

1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited documentation on the study, however, basic information is given. From the available information, similar procedure to acute oral toxicity guideline followed.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Carworth-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: inhouse
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 90-120g
- Fasting period before study: not fasted
- Diet: Rockland rat diet

Route of administration:

oral: gavage

Vehicle:

other: suspended in 0.25% agar

Doses:

Logarithmic series, differing by a factor of 2

No. of animals per sex per dose:

5 animals per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Statistics:

LD50 and fiducial range estimated by the method described by Thomson (Thomson, W.R., Bacteriol. Rev., 1947, 11, 115) and Weil (Weil, C.S., Biometrics, 1952, 8, 249).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

11 300 mg/kg bw

Based on:

test mat.

95% CL:

7 000 - 18 300

Remarks on result:

other: concentration intubated 0.2 g/ml

Confidence interval reported 7 - 18.3 g/kg bw.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral acute toxicity reported as LD50 in this study was found to be 11.3 g/kg bw (i.e. 11'300 mg/kg bw)

Executive summary:

The work of this group pre-dates range finding toxicity guidelines and provided much of the basis for their development. Their results are cited by many subsequent authoritative review bodies and are often found in SIDS and SIAR documents via secondary references. Therefore, these results (LD50 (oral, rat) = 11300 mg/kg bw) are deemed reliable.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

11 300 mg/kg bw

Quality of whole database:

The study is supported by studies on the cation (Al3+) and the alcohol (isopropanol), justified by immediate hydrolysis of the organic metal salt aluminium triisopropylate

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1991

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 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

6 hr exposure period instead of 4 hr, 14-day observation period was not clearly stated

GLP compliance:

yes

Test type:

standard acute 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: Harlan Spague-Dawley, Inc. (Indianapolis, IN)
- Age at study initiation: 9 to 11 weeks
- Housing: individually in stainless stell wire mesh cages
- Diet (e.g. ad libitum): Ground Purina Certified Rodent Chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 25
- Humidity (%): 40 to 70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel chambers with glass doors and windows
- Exposure chamber volume: Four approximately 1330-liter and one approximately 900-liter
- Source and rate of air: filtered air at a flow rate of approximately 14 air changes per hour
- Temperature, humidity in air chamber: recorded approximately 12 times during each exposure

TEST ATMOSPHERE
- Brief description of analytical method used: flame ionization gas chromatographic (GC) technique
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 6 h

Concentrations:

500, 1500, 5000, 10000 ppm

No. of animals per sex per dose:

25 animals/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: twice daily, beginning on the day of after exposure and continuing until sacrifice
- Frequency of observations and weighing: body weights were recored prior to exposure and during each test session
- Necropsy of survivors performed: no

Statistics:

The data for continuous, parametric variables were intercompared for the dose and control groups by use of Levene’s test for homogeneity of variances,by analysis of variance, and by pooled variance t-tests. The t-tests were used, if the analysis of variance was significant (P
Intra-session motor activity data was analyzed using a repeated measures analysis with dose as grouping factor and session time as the within subject factor. Group comparisons at each reporting epoch were made (as described above) if significant dose effects or time by dose interactions were observed.
The epsilon-adjustment procedure (Greenhouse-Geisser correction) was used in repeated measures analysis of motor activity data.
Frequency data from FOB tests was evaluated using Fisher’s exact
probability test.

All statistical tests were performed using BMDPm Statistical Software (Dixon, 1985 or Dixon, 1988). The fiducial limit of 0.05 was used as the critical level of significance for all tests.

Sex:

male/female

Dose descriptor:

other: transient, concentration-related narcosis and/or central nervous system sedation

Effect level:

ca. 5 000 ppm

Exp. duration:

6 h

Sex:

male/female

Dose descriptor:

other: transient, concentration-related narcosis and/or central nervous system sedation

Effect level:

ca. 10 000 ppm

Exp. duration:

6 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 10 000 ppm

Exp. duration:

6 h

Mortality:

none

Clinical signs:

other: In the 10000 ppm group, prostration, severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular tone, hypothermia, and loss of reflex function was observed 1 and 6 hours after exposure. Concentration-related decreases in mean

Body weight:

Body weight was measured at the time of behavioral testing so that any possible confounding effect that body weight might have on behavior could be assessed. Mean body weights for the five exposure groups were not statistically significantly different at any time during the study. Mean body weight tended to be lower for animals in the 10000 ppm exposure group assigned to FOB testing at the 6-hour and 24-hour post-exposure evaluations. This decrease is considered to reflect decreased food consumption during the time period when prostration and narcosis were observed.

Gross pathology:

none

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP (EC 1278/2008)

Conclusions:

LC50 > 10000 ppm

Executive summary:

Due to transient concentration-related narcosis and central nervous system sedation effects, the substance should be classified under STOT single exposure category 3, H336 - may cause drowsiness or dizziness, according to CLP classification criteria

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

24 500 mg/m³ air

Quality of whole database:

Based on the available study on the most volatile hydrolysis product isopropanol

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1948

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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Lack of methodological details

GLP compliance:

no

Remarks:

study pre-dates GLP requirements

Test type:

other: Not reported

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- Fasting period before study: Not reported
- Housing:Not reported
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum):Not reported
- Acclimation period:Not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light):Not reported


IN-LIFE DATES: Not reported

Type of coverage:

other: rubber cuff

Vehicle:

other: carbitol

Details on dermal exposure:

TEST SITE
- Area of exposure: Not reported
- % coverage: Not reported
- Type of wrap if used: rubber cuff


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not reported
- Time after start of exposure:Not reported


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Not reported, the authors stated that dosages as great as 20 ml/kg can be retained by the cuff.



VEHICLE
- Amount(s) applied (volume or weight with unit): Not reported

Duration of exposure:

24 hours

Doses:

Not reported, the authors stated that dosages as great as 20 ml/kg can be retained by the cuff.

No. of animals per sex per dose:

It is reported that the number of animals used are similar to those given oral dosages. The oral LD50 section reports groups of 6 rats.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days (or other?); Not reported
- Frequency of observations and weighing: Not reported
- Necropsy of survivors performed: Not reported
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Not reported

Statistics:

Not reported

Preliminary study:

NA

Sex:

not specified

Dose descriptor:

LD50

Effect level:

16.4 mL/kg bw

Mortality:

Not reported

Clinical signs:

other: Not reported

Gross pathology:

Not reported

Other findings:

Not reported

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)

Conclusions:

LD50 (dermal, rabbit) = 16.4 ml/kg bw = 12880 mg/kg bw

Executive summary:

The work of this group pre-dates range finding toxicity guidelines and provided much of the basis for their development. Their results are cited by many subsequent authoritative review bodies and are often found in SIDS and SIAR documents via secondary references. Therefore, these results (LD50 (dermal, rabbitt) = 16.4 ml/kg bw = 12880 mg/kg bw) are deemed reliable.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

12 880 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 isopropanol

Additional information

Upon contact with water or moisture (e.g. within mucous membranes) aluminium tri-isopropanolate hydrolyses immediately to isopropanol 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 triisopropylate hydrolyses immediately to isopropanol and aluminium 3+ cations (as hydroxide and oxyhydroxide). Hence, toxicity is determined by the toxicity of these two species and both when tested do not require classification for acute toxicity via oral, dermal or inhalation exposure. However, as isopropanol showed effects of transient concentration-related narcosis and central nervous system sedation, observed during exposure, the substance should be classified STOT SE 3, H336 May cause drowsiness or dizziness according to CLP (Regulation EC 1272/2008).