Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000-11-22 to 2000-12-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2000-08-02
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Pyrochlore
- Synonym: Stain 23 411
- Physical state: Yellow solid powder
- Analytical purity: approx. 97 %
- Batch No.: 000/04/95
- Expiration date of the batch: After year 2010
- Storage condition of test material: At room temperature
- Water solubility: Poorly soluble, insoluble in organic solvents
-Odour: none
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation: males: 34 days; females: 43 days
- Weight at study initiation: mean weight males: 185.2 g (173 g- 192 g); mean weight females: 174.8 g (170 g - 183 g)
- Fasting period before study: Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Housing: During the observation period the animals are kept in groups of 2-3 animals in MAKROLON cages (type III); Granulated textured wood (Granulate A2, J. Brandenburg, D-49424 Goldenstedt) was used as bedding material for the cages.
- Diet (ad libitum): Altromin 1324 (ALTROMIN GmbH, D-32791 Lage / Lippe)
- Water (ad libitum): Drinking water
- Acclimation period: At least 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C +/- 3 °C (maximum range)
- Relative humidity: 55 % +/- 15 % (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.8 % hydroxypropyl-methylcellulose gel
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg b.w.
no further information on the oral exposure was stated.



Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. During the follow-up period, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep, and coma. Observations on mortality were made at least once daily with appropriate actions taken to minimise loss of animals during the study. Individual body weights were recorded before admininstration of the substance and thereafter in weekly intervals up to the end of the study, and at death.
- Necropsy of survivors performed: Yes
At the end of the experiments all surviving animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. From animals which survive 24 hours or longer a microscopic examination of all organs which showed evident lesions was performed, if necessary. Autopsy and macroscopic inspection of animals which died prematurely were carried out as soon as possible after exitus.
No further information on the study design was stated.
Statistics:
The LD50 could not be calculated because no lethality occurred in this Limit test.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
Under the present test conditions a single oral administration of 2000 mg Pyrochlore/kg b.w. to rats reveal no toxic symptoms.
Body weight:
The animals gained the expected weight through the test exposure period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the present test conditions a single oral administration of 2000 mg Pyrochlore/kg b.w. to rats revealed no toxic symptoms. The animals gained the expected weight through the test exposure period. No abnormalities were noted at necrospy.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic by the oral route.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic by the oral route.