Alkanoic acid and polyoxomolybdate borate alkanoate clusters

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-11-04 to 2017-01-06

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

dated December 17th, 2001

Deviations:

yes

Remarks:

Environmental parameters : relative humidity lower than 30% (minimum = 21%) and tempearature lower than 19°C (minimum = 18°C) reported - these deviations are considered without impact on the conclusion of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Remarks:

dated October 23rd, 2015

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS, Le Genest St Isle, France
- Age at study initiation:8 or 9 weeks old at the beginning of the study
- Weight at study initiation: 196 - 226 g (fasted body weight)
- Fasting period before study: The rats were fasted approx. 1 day prior to dosing, with food being returned to the rats 4 hours after dosing.
- Housing: Animals were housed by group of three in solid-bottomed clear plycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust and was installed in conventional air conditioned animal husbandry
- Diet (ad libitum): Envigo - 2016
- Water: ad libitum
- Acclimatization period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25 °C
- Relative humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12
- Rate of air exchange : at least 10 changes per hour

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: none for the first step of the study and olive oil for second and third steps

Details on oral exposure:

In the first step of the study, the test item was administered by gavage under a volume of 1.95 mg/kg body weight (corresponding to 2g/kg, according to the calculated density) using a suitabe graduated syringue fitted with an oesophageal canula.
In the second and third steps of the study, for each step, 0.29 mL of the test item (corresponding to 300 mg) were added to 1.66 mL of olive oil. The preparations were stirred by vortex to obtain blue solutions just before the administration.
Each preparation was administered under a volume of 1.95 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 and 300 mg/kg

No. of animals per sex per dose:

2000 mg/kg: three females
300 mg/kg: 6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Daily examination: Systematic examination were carried out to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item. These observations were compared to historical control data. Observations and a mortality report were then carried out every day for 14 days.
- Periodical examinations: The animals were weighed on D0 (just before administering the test item) then on D2, D7 and D14. Weight changes were calculated and recorded.
- Examination at the end of the test: On D14, the animals were anesthetised with sodium pentoarbital and administration continued to fatal levels. Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. No organ was removed and preserved in view to microscopic examinations.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: In accordance with the O.E.C.D. test guideline n° 423, the LD50 cut-off of the test item may be considered as 500 mg/kg body weight.

Mortality:

Three mortalities were noted in animals treated at the dose of 2000 mg/kg body weight, at 24 hours post-dose.
No mortality occured during the study at the dose of 300 mg/kg body weight.

Clinical signs:

other: other: At the dose of 2000 mg/kg body weight, the mortalities were preceeded by an absence or decrease of spontaneous activity (3/3), muscle tone (3/3), righting reflex (3/3), Peeyer's reflex (3/3), associatd with bradypnea (3/3), hypothermia (3/3), eyes

Gross pathology:

At the dose of 2000 mg/Kg body weight, the macroscopic examination of the animals revealed remains important test item in the stomach (3/3), blue coloration of a forestomach and corpus (3/3) and cellular lysis of main organs in the abdomen (1/3).
At the dose of 300 mg/Kg body weight, the macrosscopic examination of the animals at the end of the study did not reveal treatment related changes.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test item is higher than 300 mg/kg body weight and lower than 2000 mg/kg body weight by oral route in the rat.
In accordance with the O.E.C.D. test guideline n° 423, the LD50 cut-off of the test item may be considered as 500 mg/kg body weight.
According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the Regulation EC n°1272/2008, the test item has to be classified in category 4. The signal word 'Warning' and hazard statement H302 'Harmful if swallowed' are required.