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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 13 April 2010 and 05 May 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tricalcium bis(orthophosphate)
EC Number:
231-840-8
EC Name:
Tricalcium bis(orthophosphate)
Cas Number:
7758-87-4
Molecular formula:
Ca.2/3H3O4P
IUPAC Name:
tricalcium diphosphate

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:
Harlan UK Limited, Bicester, Oxon, UK.

- Age at study initiation:
At the start of the study the animals were eight to twelve weeks of age.

- Weight at study initiation:
The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).

- Fasting period before study:
overnight fast immediately before dosing

- Housing:
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.

- Diet:
(2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed ad libitum throughout the study.

- Water:free access to mains drinking water

- Acclimation period:acclimatisation period of at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE

- Concentration in vehicle:
For the purpose of the study the test material was freshly prepared, as required, as a suspension in distilled water to give a dose level of 2000mg/kg bodyweight.
- Justification for choice of vehicle: Distilled water was the preferred vehicle of the test method.

MAXIMUM DOSE VOLUME APPLIED:
10ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
1 female at 2000 mg/kg
4 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes

Results and discussion

Preliminary study:
A sighting test at a dose level of 2000 mg/kg was performed.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
other: Hunched posture was noted in four animals during the day of dosing and persisted in one animal one day after dosing. No other signs of systemic toxicity were noted.
Gross pathology:
No abnormalities were noted at necropsy.

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

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

0

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

0

H

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3

Female

0

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0= No signs of systemic toxicity

H = Hunched posture


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

163

172

183

9

11

2-0 Female

157

171

190

14

19

2-1 Female

176

183

193

7

10

2-2 Female

160

170

186

10

16

2-3 Female

166

182

184

16

2

 


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:
GHS criteria not met
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 (EU CLP - Unclassified). Study is sufficient for classification and labelling purposes, in accordance with Regulation (EC) No. 1272/2008 (EU CLP).
This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). Tricalcium (orthophosphate) is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).
Executive summary:

Introduction. 

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)

Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Method. 

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 asuspensionindistilled 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.

Mortality. 

There were no deaths.

Clinical Observations. 

Hunched posture was noted in four animals. There were no other signs of systemic toxicity noted.

Bodyweight. 

All animals showed expected gains in bodyweight.

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

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 (EU CLP).