Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-10-13 to 2009-10-28
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guidelineopen allclose all
according to
OECD Guideline 401 (Acute Oral Toxicity)
according to
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
(August 1998)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:

Test material

Details on test material:
- Name of test material (as cited in study report): Aluminium hydroxide/SH-20 Muster

Test animals

Details on test animals and environmental conditions:
- Source: Charles River (EUROPE) Laboratories Inc. Toxi Coop Ltd., Budapest.
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: 194-211 g
- Fasting period before study: for 16 hours prior to treatment
- Housing: Animals were housed by groups for 3 animals per cage with deep wood sawdust bedding.
- Diet: The animals received ssniff® SM R/M-Z+H “Autoclavable complete feed for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany ad libitum. The contents of the standard diet and an analytical certificate for the quality control analysis for the batch used provided.
- Water: The animals received municipal tap water, as for human consumption, ad libitum, from 500 ml bottle ad libitum.
The water quality control analysis is performed once every three months and microbiological assessment is performed monthly by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A.u.36., Hungary).
- Acclimation period: 27 days

- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15-20 air exchange/hour.
- Photoperiod (hrs dark / hrs light): 12/12 cycle

Administration / exposure

Route of administration:
oral: gavage
polyethylene glycol
Details on oral exposure:
Al hydroxide was prepared at concentration of 200 mg/mL.
Treatment volume applied: 1 mL/100 g body weight.
Initially, three female animals were treated with a dose 2000 mg/kg administered as aluminium hydroxide. Because no mortality occurred within 24 hours after dosing, a second group of three animals received 2000 mg/kg of aluminium hydroxide. No mortality occurred in the second treatment group. According to the test guidelines, further testing was not required and the test was terminated after the 14-day observation period.
No. of animals per sex per dose:
Control animals:
Details on study design:
Duration of observation period following administration: 14 days
Frequency of observation and weighing in all animals: 30 minutes, 1,2,3,4 and 6 hours after dosing.
Observations were performed on the conditions of the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somato-motor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Frequency of weighing in all animals: day 0 (before the treatment), day 1, 7, and 14 after dosing.
At the end of study, the animals were sacrificed by exsanguinations under pentobarbital anaesthesia (Euthasol® 40 %) and gross/macroscopic examination was performed. After the examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
The mean of the body weight and body weight gain was calculated by Excel spreadsheet software.

Results and discussion

Preliminary study:
No mortality occurred in the first and second treatment group during the 14-day observation period.
Effect levels
Dose descriptor:
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Aluminium hydroxide did not cause mortality in female CRL(WI)BR rats after a single oral (gavage) administration at 2000 mg/kg.
Clinical signs:
There were no treatment-related clinical signs of intoxication following treatment or during the 14-day observation period. Soft faeces were recorded in all animals only on the day of administration.
No similar clinical signs were recorded after first day of the observation period.
Body weight:
There was no effect of treatment on body weight.
Gross pathology:
There was no effect of treatment on gross pathology.
Other findings:

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
According to CLP (1272/2008/EC classification criteria for acute oral toxicity) no classification is required.
Executive summary:

An acute oral toxicity study (limit test) was performed with aluminium hydroxide (SH-20 Muster) infemale CRL (WI)BR rats.

This study has been performed in accordance with the OECD 423 (17thDecember 2001), Commission Regulation (EC) No 440/2008, B.1 tris (L 142, 30 May 2008), OPPTS 870.1100 (EPA 712-C-98-190, August 1998) and the Principles of Good Laboratory Practice (Hungarian GLP Regulations: 9/2001. (III. 30)

Aluminium hydroxide was administered by a single oral gavage to animals after an overnight food withdrawal at a concentration of 2000 mg/mL in vehicle (PEG 400) with a treatment volume of 10 mL/kg bw.

Parameters monitored during this study included mortality, clinical signs, body weight and body weight gain.Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on days 1, 0 and 7 and before necropsy.Necroscopy was performed onall animals on day 14.

During the 14 days of the observation period, there was no mortality or clinical signs of intoxication related to aluminium hydroxide administration at 2000 mg/kg bw. Soft faeces were recorded in all treated animals at first day of administration. It was no differences in body weight gains between aluminium treated and control animals.

Macroscopic examination at the end of the observation period did not reveal any aluminium-related changes of the internal organs of the aluminium treated animals compared to the control group.

Under the conditions of this study, the acute oral median lethal dose (LD50) of the aluminium hydroxide/SH-20 Muster was above 2000 mg/kg bw in female CRL:(WI)BR rats.