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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2007-03-22 to 2007-04-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The test substance of the study is Calcium magnesium oxide, however the results are supporting also information on CaCO3MgO GLP guideline study Minor deviations without an effect on the study results: - A rationale for choosing the limit dose was not given.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
, adopted 2006-03-23
Deviations:
yes
Remarks:
see "rationale for reliability"
GLP compliance:
yes (incl. QA statement)
Remarks:
signed November 2005
Test type:
up-and-down procedure
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Calcium magnesium oxide
EC Number:
253-425-0
EC Name:
Calcium magnesium oxide
Cas Number:
37247-91-9
IUPAC Name:
37247-91-9
Details on test material:
- Name of test material (as cited in study report): Neutralac®QM3 (Calcium magnesium oxide (Burnt dolomitic lime))
- Physical state: White or off-white (beige) to grey refractory material of varying sizes: lump, granular or fine powder
- Analytical purity: Main compounds: CaO 59.5 %; MgO 37.5 %
- Batch No.: BE1107.5.2
- Expiration date of batch: January 2009
- Stability of test item: Stable under storage conditions
- Storage condition of test material: At room temperature (range of 22 +7- 5°C), moisture protected
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf/Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 181.1 to 196.7 g
- Fasting period before study: Approximately 16 to 19 hours; Food was provided again approximately 3 hours after dosing
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz) during treatment and observations
- Diet (ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 80/06 or 89/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland)
- Water (ad libitum): Community tap water from Füllinsdorf
- Acclimation period: Seven days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3°C
- Humidity: 30 - 70 %
- Air changes: 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE: Polyethylene glycol 300 (PEG 300)
- Description: Colourless viscous liquid
- Source: FLUKA Chemie GmbH, CH-9471 Buchs
- Stability of vehicle: Stable under storage conditions
- Expiration date: October 2007
- Storage conditions: At room temperature (range of 20 +/- 5°C), light protected
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. Polyethylene glycol 300 was the most suitable vehicle selected for the test item.
- Lot no.: 1300225
- Concentration in vehicle: 0.2 g/mL

MAXIMUM DOSE VOLUME APPLIED: The application volume was 10 mL/kg body weight.

DOSAGE PREPARATION:
The dose formulations were made shortly (i.e. less than 30 minutes) before each dosing occasion using a magnetic stirrer, a spatula and an Ultra-Turrax (Janke & Kunkel, D-79219 Staufen) as homogenizers. The test item was weighed into tared glass beakers on a suitable precision balance and the vehicle added (weight:volume). The pH of the freshly prepared dose formulations was mesaured at each occasion following preparation and was found to be between pH 7-8 for the test item. Temperature of the freshly prepared dose formulations was generally between 20-23 °C. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer. The stability of the test item in the vehicle was not determined in this test. This is not considerd to be required because of the short period between dose preparation and administration to the animals.
No further information on oral exposure was stated.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation of mortality/viability was made daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on the day of dosing (test day 1; with the clinical signs) and twice daily during days 2-15. Observations of body weight were made on the day prior to the administration of the test item, on the the day of administration of the test item (prior to administration of the test item), and on days 8 and 15. Observations of clinical signs were made daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.
- Necropsy of survivors performed: Yes
All animals were killed by carbon dioxide asphyxiation and discarded after macroscopic examinations have been performed.
- Other examinations performed: For clinical signs all abnormalities were recorded.
No further information on the study design was stated.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred during the study.
Clinical signs:
Slightly ruffled fur was noted in all animals at the reading performed within 30 minutes or 1 hour after administration up to 2, 3, 4 or 6 days after treatment. Hunched posture was observed at the 30-minutes or 1-hour reading up to the 2-, 3- or 5-hour reading in four of these animals and up to day 3 in the remaining animal. Slight sedation was noted at the 30-minutes reading in one animal, from the 30-minutes reading up to the 3- or 5-hour reading in two animals and up to day 3 in one animal.
Clinical signs were shown to be reversible until scheduled sacrifice on day 15.
Body weight:
The body weight of the female animals used was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose for the test item Neutralac®QM3 (Calcium magnesium oxide (Burnt dolomitic lime)) after single oral administration to female rats, observed over a period of 14 days is: LD50 (rat): greater than 2000 mg/kg body weight.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified.

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