Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 April - 27 May 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Modern guideline conform study performed in GLP certified laboratory

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Test material form:
solid: particulate/powder
Details on test material:
Neodymium fluoride oxide, magnesium doped
Batch No.: 2016JAN-15kg
Description: white to bluish white powder
Expiration date: January 1, 2020
Storage: At room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Species and strain: Crl:WI BR rats
Source: TOXI COOP ZRT. Cserkesz u. 90. 1103 Budapest, Hungary
Hygienic level at arrival: SPF
Hygienic level during the study: Good conventional
Justification of strain: The Wistar rats as a rodent is one of the standard species of acute toxicity studies
Number of animals: 3 animals/group
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 8 weeks old in first and second step
Body weight range at starting (first step): 204 - 206 g
Body weight range at starting (second step): 199 - 209 g
Acclimatization time: 5 days in first step and 6 days in second step
Animal health: Only healthy animals were used for the study. Health status was certified by the study director.
Room: 13/1
Housing: Group caging (3 animals/cage)
Cage type: Type II polypropylene/polycarbonate.
Bedding: Laboratory bedding.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: above 10 air exchanges/hour by central air-condition system.

The temperature and relative humidity were recorded daily during the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Aqua purificata Ph.Hg. VIII. Batch number: 1511-5526 Date of expiration: 26.05.2016 Produced by: Pharma Produkt Kft
Details on oral exposure:
A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.
Doses:
2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats.
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix VII) was met.

Statistics:
The method used is not intended to allow the calculation of a precise LD50 value. The test item was ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423
The frequency of the clinical symptoms was summarized in tabular form. The mean of the body weight and body weight gain were calculated by Excel spreadsheet software. Necropsy findings were described and summarised in tabular form.

Results and discussion

Preliminary study:
Starting dose was selected on the basis of the available information about the test item.
The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats.
Effect levels
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred at 2000 mg/kg bw single oral dose of Neodymium fluoride oxide, magnesium doped. All female rats in step 1 and step 2 survived until the end of the 14-day observation period.
Clinical signs:
No treatment related symptoms were observed throughout the 14-day post-treatment period in groups 1 and 2 treated with 2000 mg/kg bw dose.
Body weight:
The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study.
Gross pathology:
No pathological changes were found related to the effect of the test item during the macroscopic examination of animals treated with 2000 mg/kg bw dose.
Other findings:
Severe hydrometra was observed in female No.: 1593 of the group 1 and in female No.: 1597 of the group 2. Slight hydrometra was found in animal No.: 1600 of group 2. Hydrometra is physiological finding and connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals treated with 2000 mg/kg bw dose.

Any other information on results incl. tables

Dose
(mg/kg bw)

Mortality
(dead/treated)

LD50
(mg/kg bw)

GHS
category

2000

0/6

above 2000

5 or unclassified

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
No lethality was noted at single oral dose of 2000 mg/kg bw.
The method used is not intended to allow the calculation of a precise LD50 value.
LD50 (mg/kg bw) is above 2000; GHS category 5 or unclassified
Executive summary:

An acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, therefore treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix VII) was met. No clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal. The body weight development was undisturbed in all animals. All organs of the animals treated with 2000 mg/kg bw dose proved to be free of treatment related gross pathological changes. The method used is not intended to allow the calculation of a precise LD50value. The LD50 of Neodymium fluoride oxide is above 2000 (mg/kg bw), GHS category 5 or unclassified