Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 April 2010 to 25 May 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
yes
Remarks:
no analysis conducted on test material after formulation to determine stability
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): dineodymium tricarbonate
- Substance type: extremely pale purple powder
- Physical state: solid
- Lot/batch No.: not provided, received 15 Feb 2010
- Expiration date of the lot/batch: 15 Jan 2011
- Storage condition of test material: room temperature in the dark over silica gel

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories, UK., Ltd, Oxon, UK
- Age at study initiation: 8-12 weeks of age
- Weight at study initiation: did not exceed ± 20% of the initial bodyweight of any previously dosed animal
- Fasting period before study:
- Housing: suspended solid floor polypropylene cages furnished with wood flakes
- Diet (e.g. ad libitum): ad libitum, 2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon UK
- Water (e.g. ad libitum): ad libitum, free of contaminants as analyzed
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 deg C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2000 mg/kg in water
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: not stated
- Lot/batch no. (if required): not stated
- Purity: not stated

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

DOSAGE PREPARATION (if unusual): test material was freshly prepared as a suspension in distilled water. Test material formulated 2 h before being applied and assumed to be stable.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: limit dose for classification
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
Animals gavaged only once. Volume adminstered was calcualted based on its fasted bodyweight at time of dosing. Bodyweights recorded on day 0, 7 and 14. At end of observation, animals subjected to gross necropsy; no tissues were examined. 1 rat was chosen with the starting dose, in the absence of toxicity at 2000 mg/kg, 4 more rats were treated at the same dose.

Results and discussion

Preliminary study:
No deaths were observed in the primary animal
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no deaths
Mortality:
No deaths were observed
Clinical signs:
No signs of toxicity
Body weight:
All animals showed expected gains in bodyweight over the observation period
Gross pathology:
No abnormalities noted

Any other information on results incl. tables

Table1            Individual Clinical Observations and Mortality Data

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

  Table2            Individual Bodyweights and Bodyweight Changes

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

1-0 Female

185

192

200

7

8

2-0 Female

183

200

216

17

16

2-1 Female

181

203

225

22

22

2-2 Female

176

192

209

16

17

2-3 Female

180

197

213

17

16

Table3            Individual Necropsy Findings

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

1-0 Female

Killed Day 14

No abnormalities detected

2-0 Female

Killed Day 14

No abnormalities detected

2-1 Female

Killed Day 14

No abnormalities detected

2-2 Female

Killed Day 14

No abnormalities detected

2-3 Female

Killed Day 14

No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System Unclassified).
Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following: OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (adopted 17 December 2001) and Method B1 bis acute toxicity (oral) of commission regulation EC No. 440/2008. Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test material, as asuspension in distilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths, signs of toxicity, changes in body weight or gross abnormalities. The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System-Unclassified).