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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Somewhere during 1978
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other:
Remarks:
Rel. 3 because information on substance identity and composition is lacking. Batch No. is given and method is comparable to guideline 401. If substance identity and composition is known reliability can turn into 2 (limited reported study, pre-GLP).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Principles other than guideline:
- no necropsy of survivors
- very high concentrations tested
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Test material form:
solid - liquid: aqueous solution
Details on test material:
- Name of test material (as cited in study report): Chlorosulfate basique d'aluminium
- Physical state: brown-grey liquid
- Other: received 125 ml

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: IFFA CREDO
- Age at study initiation: no info
- Weight at study initiation: 145 - 165 g
- Fasting period before study: approximately 19 hours
- Housing: 5 per cage
- Diet (e.g. ad libitum): IFFARAT
- Water (e.g. ad libitum): water
- Acclimation period: no info


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 50 ± 10
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): no info


IN-LIFE DATES: No info

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: not applicable


MAXIMUM DOSE VOLUME APPLIED: 14 ml/kg


DOSAGE PREPARATION (if unusual): not applicable


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not applicable
Doses:
Main study: 7.2 g/kg, 9.6 g/kg, 12 g/kg, 14.4 g/kg, 16.8 g/kg
Preliminary study: 6 g/kg, 12 g/kg, 24 g/kg
No. of animals per sex per dose:
Main study: 5
Preliminary study: 2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations after 15 minutes, 1, 2 and 6 hours and every day during 14 days and autopsy of the animals which died. Weighing on Day 0, 1, 2, 4, 7 and 14.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight
Statistics:
Calculation of the LD50 by 3 methods:
- Probit method (Bliss - 1935)
- The method of Litchfield and Wilcoxon (1949)
- The method of arcsinus
1. Bliss, C.I. The comparison of dosage-mortality data - Ann. Appl. Biol. 22, 307-333, 1935
Bliss, C.I. The calculation of the dosage-mortality curve - Ann. Appl. Biol. - 22, 134-167, 1935
Bliss, C.I. The determination of the dosage-mortality curve from small numbers - Quart. J; Pham. and Pharmacol., 11 192-216,1935
2. Litchfield J.T., Wilcoxon J.R. and F.: A simplified method of evaluating dose-effect experiments. The Journal of Pharmacology and Experimental Therapeutics, 96, 2, 99-113, 1949

Results and discussion

Preliminary study:
Mortality:
- Dose group 6 g/kg: no mortality
- Dose group 12 g/kg: 2 female animals died
- Dose group 24 g/kg: 2 male and 2 female animals died
Clinical signs:
- Dose group 24 g/kg: at 1 hour observation zero spontaneous activity, absence of reflex overturning, piloerection.
- Dose group 12 g/kg: at 1 hour observation apathy, piloerection, motor difficulties and rapid breathing. After 1 day: Prostration and piloerection among the survivors.
- Dose group 6 g/kg: Apathy and piloerection.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
11 800 mg/kg bw
95% CL:
> 10 460 - < 13 360
Remarks on result:
other: Based on Litchfield and Wilcoxon
Mortality:
- Dose group 7.2 g/kg: no mortality
- Dose group 9.6 g/kg: no mortality
- Dose group 12 g/kg: 2 males and 4 females died
- Dose group 14.4 g/kg: 5 males and 4 females died
- Dose group 16.8 g/kg: 5 males and 5 females died
Clinical signs:
- Dose group 7.2 g/kg: Slowdown in spontaneous activity (2 h); at 6 h also piloerection; after 1 day normal behaviour.
- Dose group 9.6 g/kg: Same symptoms as the previous dose.
- Dose group 12 g/kg: low spontaneous activity (2 h); low activity, depression and piloerection (6 h); low activity, depression among all the females and one male, piloerection, one female had blood in her urine, one male had bladder haemorrhagic fever (Day 1); persistence of a slight piloerection among the survivors on Day 3; the surviving animals showed normal behaviour on Day 4.
- Dose groups 14.4 g/kg and 16.8 g/kg: slowdown in spontaneous activity (1 h); also depression, piloerection and staggering gait after 6 hours; on Day 1 the remaining animal died.
Body weight:
Bodyweight gains per dose group were recorded for all surviving rats.
Gross pathology:
- Dose group 12 g/kg: the autopsy by two males and one female showed bleeding of their stomachs and a contracted jejunum.
- Dose groups 14.4 and 16.8 g/kg: no info
Other findings:
No.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute oral median lethal dose to rats of Chlorosulfate basique d’aluminium (WAC®) was found to be 11800 mg/kg bodyweight. Based on the assumption that approximately 20% of this test material consists of salts the acute oral median lethal dose to rats of the salts is 2360 mg/kg bodyweight. According to OECD-GHS the salts of chlorosulfate basique d’aluminium is classified as category 5.
Executive summary:

An acute oral toxicity was performed. The method of the study shows similarities to OECD Guideline 401 (Acute Oral Toxicity), and is however not performed according to GLP standards. The test material, Chlorosulfate basique d’aluminium (WAC®) was evaluated for its acute oral toxicity potential in rats when administered as gavage doses at levels of 7200, 9600, 12000, 14400, 16800 mg/kg bw to 5 males and 5 females per dose group.

At 12000 mg/kg 6 animals died, at 14400 mg/kg 9 animals died and at 16800 mg/kg 10 animals died.

Clinical signs of toxicity included pilo-erection and depression; recovery in surviving animals was complete not later than Day 4.

Gross pathologic examination for the deceased animals revealed bleeding of the stomachs.

 

Acute oral LD50(test material) = 11800 mg/kg bw.

Based on the assumption that approximately 20% of this test material consists of salts, acute oral LD50(salts) = 2360 mg/kg bw

 

Under the test conditions, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and classified in category 5 according to the GHS.

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