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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 3, 2017 - January 18, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
calcium tetrahydrate chloride [2-(trimethylazaniumyl)ethyl] phosphate
Cas Number:
72556-74-2
Molecular formula:
C5H21CaClNO8P
IUPAC Name:
calcium tetrahydrate chloride [2-(trimethylazaniumyl)ethyl] phosphate
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
SPF Caw
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: JANVIER LABS (53940 Legenest St. Isle - France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks old
- Weight at study initiation: 197.3 ± 9.4 g
- Fasting period before study: overnight
- Housing: Groups 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 (e.g. ad libitum): Foodstuff (ENVIGO -2016) ad libitum
- Water (e.g. ad libitum): Tap-water from public distribution system ad libitum. Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas- Eurofins (France)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19ºC - 25ºC. A temperature lower than 19ºC was registered on 3 and 7 of January 2017. The minimum value measured was 22%.
- Humidity (%): 30% - 70%. A relative humidity lower than 30% was registered on 3, 4, 5, 6, 7, 8, 17 and 18 of January 2017. The minimum value measured was 22%.
- Air changes (per hr): 10 changes/hour
- Photoperiod (hrs dark / hrs light): 12 h light (7 - 19 h) / 12 h darkness

IN-LIFE DATES: From: 3 January 2017 To: 18 January 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: DMSO produced the most suitable formulation at the requested concentration.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/Kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Without preliminary information. The selected starting dose is 2000 mg/kg body weight.
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
yes
Remarks:
Study No. TAO423-2016-004 (see "Other information on results").
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systemic observations at 30 min, 1h, 3h, 4h, 24h, 48h after adminitrationand daily during 14 days. Weighing: on day Day 0 (just before administering the test item) then on Day 2, Day 7, and Day 14.
- Necropsy of survivors performed: yes. At termination, macroscopic observation was observed. Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. Parameters examined: Oesophagus, Stomach, Duodenum, Jejunum, Ileon, Caecum, Colon, Rectum, Spleen, Liver, Thymus, Trachea, Lungs, Heart, Kidneys, Urinary Bladder, Ovaries, Uterus, Treatment Area, Adrenals and Pancreas.
- Other examinations performed:
Clinical signs: Spontaneous activity, Preyer's reflex (noise), Respiratory rate, Convulsions, Tremors, Body temperature, Muscle tone, Palpebral opening, Pupil appearance, Salivation, Lachrymation, Righting reflex, Back hair appearance, Mortality.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs related to the administration of the test item were observed during the study.
Body weight:
The body weight evolution of the animals remained normal during the study.
Gross pathology:
The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Any other information on results incl. tables

Table 1. Test item at 2000 mg/kg bw. Body weight and weight gain in grams.

FEMALES

D0

D2

D2-D0

D7

D7-D0

D14

D14-D0

Rf 0839

190

212

22

237

47

251

61

Rf0840

199

225

26

243

44

259

60

Rf 0841

182

202

20

222

40

244

62

Rf 0854

204

221

17

245

41

260

56

Rf 0855

206

217

11

239

33

262

56

Rf 0856

203

224

21

243

40

269

66

MEAN

197.3

216.8

19.5

238.2

40.8

257.5

60.2

Standard deviation

9.4

8.7

5.1

8.4

4.7

8.8

3.8

GENERAL APPEARANCE BEFORE AUTOPSY: Normal

Observations: Nothing to report.

Current control Study:

The study identified No. TAO423 -2016 -004 was performed to assess the comportament of the strain of rat used at the laboratory in the environment and to give additional historical data. The method was designed to meet the requirements of the following: OECD Guideline No. 423 (December 17th, 2001) and Method B1 tris of Council regulation No. 440/2008.

Test item : Distilled water

Study dates: 20 September 2016 to 04 October 2016

Results:

- Clinical examinations: Nothing to report. Animal normal (3/3)

- Bodyweight evolution: normal during the test.

- Necropsy: No treatment related changes were observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. 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.
Executive summary:

The acute oral toxicity of the test ite has been tested in accordance with OECD 423 and EU method B.1 tris, following GLP. The test item was administered to a group of 6 female Sprague-Dawley rats at the dose of 2000 mg/kg body weight by oral gavage. All animals were observed immediately after administration for the onset of any toxic signs and once daily thereafter for 14 days.No mortality occurred during the study and the body weight evolution of the animals remained normal during the study. No clinical signs related to the administration of the test item were observed during the study. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes. No other signs of systemic toxicity were noted. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. 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.