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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2021-09-22 to 2021-12-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2021
Report date:
2021

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
dated December 17th, 2001
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Salt reaction of cobalt(2+) and C2/C8/C20 carboxylates
EC Number:
942-548-1
Molecular formula:
(CnH2n-102/Cn’H2n’-1O2) Co with n, n’ = 2 or 8 or 20
IUPAC Name:
Salt reaction of cobalt(2+) and C2/C8/C20 carboxylates
Test material form:
solid: pellets

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Saint-Germain-Nuelles, France
- Age at study initiation:8 weeks old at the beginning of the study
- Weight at study initiation: 183 - 208 g
- 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 - 2014
- 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:
olive oil
Details on oral exposure:
Olive oil (vehicle) was chosen as it produced the most suitable formulation at the requested dose of 300 mg/Kg body weight.
For steps 1 & 2 (300 mg/Kg body weight), the preparations were stirred using a vortex for 3 minutes, by Ultraturrax for 3 minutes and manually to obtain black suspensions just before the administration.
For Step 3 (2000 mg/Kg body weight), the preparation was stirred using a vortex for 2 minutes and by Ultraturrax for 3 minutes at 10 000 rpm to obtain a black homogeneous suspension just before the administration.
For Step 4 (2000 mg/Kg body weight), the preparation was stirred using a vortex to obtain a black homogeneous suspension just beofre the administration.
Each preparation was administered by gavage, in a single dose, under a volume of 10 mL/ kg body waight (accounting to the calculated density) using a suitable syringe graduated fitted with an oesophageal metal canula.
Doses:
300 and 2000 mg/Kg body weight
No. of animals per sex per dose:
300 mg/Kg body weight: 6 females
2000 mg/Kg body weight: 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 30 minutes, 1 hour +/- 6 minutes; 3 hours +/- 30 minutes, 4 hours +/- 30 minutes, 24 and 48 hours +/- 2 hours after administration of the test item and continued daily for 14 days. This examination focuses particularily on a list of symptoms recoreded as 'present' or 'absent'. 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. The body weight evolution of animals treated with the test item is compared with the body weight evolution of the control group.
- Examination at the end of the test: On D14, the animals were anesthetised with sodium pentoarbital. 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:
> 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 2500 mg/kg body weight by oral route in the rat.
Mortality:
No mortality occured during the study at the dose of 300 mg/Kg body weight.
One mortality (1/6) was noted on day 6 at the dose of 2000 mg/Kg body weight.
Clinical signs:
other: 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. At the dose of 2000 mg/kg body weight, the mortality was preceeded by a decrease of spontaneous activity at 1-hour post-
Gross pathology:
At the dose of 300 mg/Kg body weight, the macroscopic examination of the animals at the end of the study did not reveal treatment related changes.
At the dose of 2000 mg/Kg body weight, the macroscopic examination of the dead animal revealed thin stomach membrances and advanced lysis of the digestive system, the urinary system and the reproductive system. The macroscopic examination at the end of the study revealed a thin proventricular (5/5) and fundic (2/5) wall, disintegrated when touched (1/5) with red spot (1/5) and transparent mass (1/5) on the fundic wall.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The LD50 of the test item is higher 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 2 500 mg/kg body weight by oral route in the rat..
In accordance with the Regulation EC n°1272/2008 on classification, labelling and packaging of substances and mixture, the test item does not have to be classified. No signal word or hazard statement is required.