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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:
17/07/2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Remarks:
A temperature higher than 25°C was registered on 17 and 18 April 2018. The maximum value measured was 26°C. This deviation is considered as without impact on the conclusion of the study.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and batch No.of test material: Bernardy SAS, Batch No 1601762
- Production date of the batch : 29 September 2016
- Expiration date of the batch: 29 September 2019
- Purity test date: 30/09/2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in opaque plastic flask
- Stability under test conditions: stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No (Olive oil was added for the oral administration)

FORM AS APPLIED IN THE TEST
White solid powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: supplied by Elevage JANVIER LABS (53940 Le Genest St Isle – France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: At the beginning of the study, the animals were 8 or 9 weeks old.
- Weight at study initiation: Mean = 199.3grams (standard deviation 11.2 grams)
- Fasting period before study: Food was removed on day 1 and then redistributed 4 hours after the test item administration.
- Housing: Healthy female rats were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry.
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: acclimatization period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ranges of 19°C to 25°C
- Humidity (%): ranges of 30% to 70%,
- Air changes (per hr): at least ten changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (07.00 to 19.00) and twelve hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: In the first and second steps of the study, 0.3041 g and 0.3005 g of the test item were weighed and olive oil was added to two 10mL volumetric flasks. In the third and fourth steps of the study, 2.0066 g and 2.0004 g of the test item were weighed and olive oil was added to two 10 mL volumetric flasks.
- Amount of vehicle: olive oil was added and each preparation was administered under a volume of 10 mL/kg body weight
- Justification for choice of vehicle: Olive oil was chosen as it produced the most suitable formulation at the requested concentration.

MAXIMUM DOSE VOLUME APPLIED:
The first tested dose was 300 mg/kg body weight. The second dose was 2000 mg/kg body weight.

DOSAGE PREPARATION:
Olive oil was added and each preparation was administered under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula. Just before the administration, the preparations were stirred by vortex to obtain yellow thin homogeneous solutions.

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose was determined according to the toxicological information publicly available on analogue substances.
Doses:
Two doses were tested : 300 mg/kg body weight and 2000 mg/kg body weight.
No. of animals per sex per dose:
3 female per step (2 steps per dose)
Control animals:
yes
Remarks:
Three animals, received the control item olive oil. Nothing to report. Animal normal (3/3)
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on day D0 (just before administering the test item) then on day 2, day 7, and day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examinations of organs in the necropsy.

Results and discussion

Preliminary study:
No preliminary study. The starting dose was determined according to the toxicological information publicly available on analogue substances.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No effect observed.
Clinical signs:
No effect observed.
Body weight:
No effect observed.
Gross pathology:
No effect observed.

Any other information on results incl. tables

Application: 300 mg/kg body weight (oral route)

Table 1

Observations

Females

Females

T0 + 30 minutes

T0 + 1 hour

T0 + 3 hours

T0 + 4hours

Rf

2467

Rf

2468

Rf

2469

Rf

2470

Rf

2471

Rf

2472

Spontaneous activity

N

N

N

N

N

N

Preyer’s reflex (noise)

N

N

N

N

N

N

Respiratory rate

N

N

N

N

N

N

Convulsion

N

N

N

N

N

N

Tremors

N

N

N

N

N

N

Body temperature

N

N

N

N

N

N

Muscle tone

N

N

N

N

N

N

Palpebral opening

N

N

N

N

N

N

Pupil appearance

N

N

N

N

N

N

Salivation

N

N

N

N

N

N

Lachrymation

N

N

N

N

N

N

Righting reflex

N

N

N

N

N

N

Back hair appearance

N

N

N

N

N

N

MORTALITY

0

0

0

0

0

0

Remarks

None

None

 

Table 2

Observations

Females

Females

T0 + 30 minutes

T0 + 1 hour

T0 + 3 hours

T0 + 4hours

Rf

2467

Rf

2468

Rf

2469

Rf

2470

Rf

2471

Rf

2472

Spontaneous activity

N

N

N

N

N

N

Preyer’s reflex (noise)

N

N

N

N

N

N

Respiratory rate

N

N

N

N

N

N

Convulsion

N

N

N

N

N

N

Tremors

N

N

N

N

N

N

Body temperature

N

N

N

N

N

N

Muscle tone

N

N

N

N

N

N

Palpebral opening

N

N

N

N

N

N

Pupil appearance

N

N

N

N

N

N

Salivation

N

N

N

N

N

N

Lachrymation

N

N

N

N

N

N

Righting reflex

N

N

N

N

N

N

Back hair appearance

N

N

N

N

N

N

MORTALITY

0

0

0

0

0

0

Remarks

None

None

 

  

Application: 2000 mg/kg body weight (oral route)

Table 3

Observations

Females

Females

T0 + 30 minutes

T0 + 1 hour

T0 + 3 hours

T0 + 4hours

Rf

2476

Rf

2477

Rf

2478

Rf

2487

Rf

2488

Rf

2489

Spontaneous activity

N

N

N

N

N

N

Preyer’s reflex (noise)

N

N

N

N

N

N

Respiratory rate

N

N

N

N

N

N

Convulsion

N

N

N

N

N

N

Tremors

N

N

N

N

N

N

Body temperature

N

N

N

N

N

N

Muscle tone

N

N

N

N

N

N

Palpebral opening

N

N

N

N

N

N

Pupil appearance

N

N

N

N

N

N

Salivation

N

N

N

N

N

N

Lachrymation

N

N

N

N

N

N

Righting reflex

N

N

N

N

N

N

Back hair appearance

N

N

N

N

N

N

MORTALITY

0

0

0

0

0

0

Remarks

None

None

 

Table 4

Observations

Females

Females

T0 + 30 minutes

T0 + 1 hour

T0 + 3 hours

T0 + 4hours

Rf

2476

Rf

2477

Rf

2478

Rf

2487

Rf

2488

Rf

2489

Spontaneous activity

N

N

N

N

N

N

Preyer’s reflex (noise)

N

N

N

N

N

N

Respiratory rate

N

N

N

N

N

N

Convulsion

N

N

N

N

N

N

Tremors

N

N

N

N

N

N

Body temperature

N

N

N

N

N

N

Muscle tone

N

N

N

N

N

N

Palpebral opening

N

N

N

N

N

N

Pupil appearance

N

N

N

N

N

N

Salivation

N

N

N

N

N

N

Lachrymation

N

N

N

N

N

N

Righting reflex

N

N

N

N

N

N

Back hair appearance

N

N

N

N

N

N

MORTALITY

0

0

0

0

0

0

Remarks

None

None

 

Body weight and weight gain in grams

Table 5

Females

D0

D2

D2-D0

D7

D7-D0

D14

D14-D0

Rf 2467

189

208

19

226

37

245

56

Rf 2468

206

224

18

234

28

265

59

Rf 2469

185

209

24

231

46

265

80

Rf 2470

196

220

24

229

33

259

63

Rf 2471

214

231

17

252

38

274

60

Rf 2472

206

209

3

240

34

281

75

MEAN

199.3

216.8

17.5

235.3

36.0

264.8

65.5

Standard deviation

11.2

9.6

7.7

9.5

6.0

12.4

9.7

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item Magnesium oxalate is higher than 2000 mg/ kg body weight by oral route in the rat.
In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be considered to be higher than 5000 mg/ kg body weight by oral route in the rat.
The test item Magnesium oxalate does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.
No signal word or hazard statement is required.
Executive summary:

The test item Magnesium oxalate was administered to a group of 6 female Sprague Dawley rats at the dose of 300 mg/kg body weight and then to a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight. The experimental protocol was established according to the official method as defined in the O.E.C.D. Test Guideline No. 423 dated December 17th, 2001 and the test method B.1tris of the Council regulation No. 440/2008.

No mortality was noted in the animals treated at the dose of 300 mg/kg body weight. No clinical signs related to the administration of the test item were observed during the study. The body weight evolution of the animals remained normal during the study. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

No mortality was noted in the animals treated at the dose of 2000 mg/kg body weight. No clinical signs related to the administration of the test item were observed during the study. The body weight evolution of the animals remained normal during the study. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

In conclusion, the LD50 of the test item Magnesium oxalate is higher than 2000 mg/ kg body weight by oral route in the rat. In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be considered to be higher than 5000 mg/ kg body weight by oral route in the rat. The test item Magnesium oxalate does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures. No signal word or hazard statement is required.