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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:
key study
Study period:
The study was performed between 14 October 2009 and 04 November 2009.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of GLP inspection:19/08/2009 Date of Signature on GLP certificate:26/11/2009
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: granular solid
Details on test material:
Sponsor's identification: Trisodium orthophosphate
Description: white granular solid
Batch number: 446/09
Date received: 18 September 2009
Storage conditions: 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 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 (e.g. ad libitum):
(2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed ad libitum throughout the study.

- Water (e.g. ad libitum):free access to mains drinking water

- Acclimation period:acclimatisation period of at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
19 to 25°C

- Humidity (%):
30 to 70%

- Air changes (per hr):
The rate of air exchange was at least fifteen changes per hour.

- 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.


IN-LIFE DATES: From: Day 1 To: Day 14

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.

- Amount of vehicle (if gavage):
Not stated

- Justification for choice of vehicle:
Distilled water was the preferred vehicle of the test method.

- Lot/batch no. (if required):
Not stated

- Purity:
Not stated


MAXIMUM DOSE VOLUME APPLIED:
10ml/kg


DOSAGE PREPARATION (if unusual):
Not applicable

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:
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 a suspension 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.
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


- Other examinations performed:
Clinical signs, body weight.

Results and discussion

Preliminary study:
A sighting test at a dose level of 2000 mg/kg was performed.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: 95% confidence limits not given in study report.
Mortality:
There were no deaths.
Clinical signs:
Signs of systemic toxicity noted in four animals were hunched posture and noisy respiration. There were no signs of systemic toxicity noted in one animal.
Body weight:
Animals showed expected gains in bodyweight except for two animals which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
- Organ weights:
Not recorded

- Histopathology:
Not recorded

- Potential target organs:
Not recorded

- Other observations:
None

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

Rn

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

Rn

HRn

HRn

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

Rn

HRn

HRn

HRn

HRn

HRn

H

0

0

0

0

0

0

0

0

0

0

0

2-3

Female

Rn

H

H

H

H

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

186

191

194

5

3

2-0 Female

178

181

196

3

15

2-1 Female

187

178

188

-9

10

2-2 Female

158

156

168

-2

12

2-3 Female

174

184

193

10

9

 


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


0= No signs of systemic toxicity

H = Hunched posture

Rn = Noisy respiration

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 Classification - not classified).

This study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement for this endpoint in addition the study is deemed acceptable for classification and labelling according to Regulation (EC) No 1272/2008 (EU CLP). This study supports the conclusion that sodium and potassium orthophosphates exhibit low systemic toxicity.
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 B1bisAcute 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. 

Signs of systemic toxicity noted in four animals were hunched posture and noisy respiration. There were no signs of systemic toxicity noted in one animal.

Bodyweight. 

Animals showed expected gains in bodyweight except for two animals which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.

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 - not classifed )