Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 11 March 2010 and 06 April 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:
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)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Remarks:
HsdRccHan®™:WIST®™
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: mean 177 g
- Fasting period before study: overnight
- Housing: n groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes
- Diet: ad libitium - 2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK
- Water: ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Using available information on the toxicity of the test material, 2009 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight) was chosen as
the starting dose.

Dose Level(mg/kg) Concentration(mg/ml) Dose Volume(ml/kg) Number of Rats
Female
2009* 200.9 10 1

In the absence of toxicity at a dose level of 2009 mg/kg, an additional group of animals was treated as follows:

Dose Level(mg/kg) Concentration(mg/ml) Dose Volume(ml/kg) Number of Rats
Female
2009* 200.9 10 4

A total of five animals were therefore treated at a dose level of 2009 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight) in the study.
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was
calculated according to its fasted bodyweight at the time of dosing.


Doses:
2009 mg/kg (equivalent to 2000 mg active ingredient /kg bodyweight)
No. of animals per sex per dose:
5
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 weigh

Results and discussion

Preliminary study:
A sighting test at a dose level of 2009 mg/kg (equivalent to 2000 mg active ingredient /kg bodyweight) was performed.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Individual bodyweights and bodyweight changes are given in Table 2.
Gross pathology:
No abnormalities were noted at necropsy.
Individual necropsy findings are given in Table 3.

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

2009*

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

*= Equivalent to 2000 mg active ingredient/kg bodyweight

0= No signs of systemic toxicity


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

2009*

1-0 Female

169

176

188

7

12

2-0 Female

165

178

189

13

11

2-1 Female

169

182

190

13

8

2-2 Female

187

198

207

11

9

2-3 Female

195

210

216

15

6

*= Equivalent to 2000 mg active ingredient/kg bodyweight

 

Table3              Individual Necropsy Findings

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2009*

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

*= Equivalent to 2000 mg active ingredient/kg bodyweight

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 (Not classified - EU CLP).
Magnesium hydrogenorthophosphate is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP). Study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement for this endpoint. Study is sufficient for classification and labelling purposes, in accordance with 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 17th 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 2009 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight), an additional four fasted female animals were given a single oral dose of test material, as asuspensionindistilled water, at a dose level of 2009 mg/kg bodyweight (equivalent to 2000 mg active ingredient/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. 

There were no signs of systemic toxicity.

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 2009 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight) (Not classified - EU CLP)