Lithium nickel potassium oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study completed March 20, 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

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000 as this in line with OECD 423.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Lithium nickel potassium oxide

Cas Number:

210352-95-7

Molecular formula:

Li.K.Ni.O.H2O

IUPAC Name:

Lithium nickel potassium oxide

Test material form:

solid: particulate/powder

Details on test material:

Lithium nickel potassium oxide (KDLNO)
CAS Number:
210352-95-7
Appearance/Physical state:
Black powder
Storage: Room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats.

Sex:

female

Details on test animals or test system and environmental conditions:

Nulliparous and non-pregnant female animals were used for the test as suggested by the OECD guideline when there is no indication that male animals are likely to be more sensitive to the acute effects of the test item. They were young adult animals (female animals approx. 10 weeks and of comparable weight (± 20% of the mean weight)). There was an acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet. Rats were identified by individual identification by cage cards and tail marking.

The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 22°C ± 3°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.

Air changes per hour
Approx. 10
Day / night rhythm:
12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage:
Makrolon cage, type III
Number of animals per cage:
Single housing
Feeding:
VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
Drinking water:
Tap water ad libitum
Bedding:
H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
Enrichment:
Wooden gnawing blocks (Type NGM E-022); ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria

The feed used in the study was assayed for chemical and microbial contaminants by the manufacturer in quarterly intervals. Results are archived by Bioassay.

The drinking water was regularly assayed for contaminants by the municipal authorities of Heidelberg. The German Drinking Water Regulation of Dec. 5, 1990 served as the guideline for maximum tolerable contaminants.

The bedding and enrichment were regularly assayed for contaminants (chlorinated hydrocarbons and heavy metals).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

Chosen due to good homogeneity of the test material in corn oil

Details on oral exposure:

The test item formulation was prepared shortly before application by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer. Additionally, the homogeneity of the test item preparation during application was ensured by stirring with a magnetic stirrer. The stability of the test item in the vehicle was determined indirectly by concentration control analysis. For this purpose, the samples taken were stored at room temperature over the maximum duration of the administration period, subsequently deep-frozen and sent for analysis.

The homogeneity of the test item preparation was determined indirectly by concentration control analysis.

Route of administration:
Single oral administration by gavage.
Fasting period:
Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
Time of day of administration:
In the morning
Observation period:
14 days
Body weight determination:
Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation and on the day of death starting with study day 1.

Doses:

SELECTION OF DOSES/CONCENTRATIONS
A starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals.
As all animals died, a dose of 500 mg/kg bw was administered to 3 female rats in the second step.
Because no mortality occurred, a further dose of 500 mg/kg bw was administered to another group of 3 female animals in the third step.

No. of animals per sex per dose:

3 females per dose

Control animals:

no

Details on study design:

The objective of this study was to assess the acute oral median lethal dose following a single oral administration to female Wistar rats followed by a 14 day observation period.
The study was performed in rats, because this species has been shown to be suitable for this type of study and is recommended by the test guidelines.

Statistics:

In the single 2000 mg/kg bw test group all animals died on day 3 or 5 after administration.
No mortality occurred in both 500 mg/kg bw test groups.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 500 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

In the single 2000 mg/kg bw test group all animals died on day 3 or 5 after administration.
No mortality occurred in both 500 mg/kg bw test groups.

Clinical signs:

other: Clinical signs in the single 2000 mg/kg test group revealed in all animals an impaired general state and piloerection from hour 2 or 4 until hour 5 and again from day 2 until day 3 after administration. Black discolored faeces was seen on day 1 in all ani

Gross pathology:

The following macroscopic pathologic findings were observed in the animals that died (single 2000 mg/kg bw test group, 3 females):
o Stomach filled with blackish liquid, discoloration of the stomach contents
o Dark discolored small and large intestine
There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (6 females of both 500 mg/kg bw. groups).

Other findings:

The following test substance-related clinical observations were recorded, clinical signs occurred within the first 5 days after administration:
2000 mg/kg (single test group):
 Mortality in all animals
 Impaired general state in all animals
 Dyspnea in all animals
 Piloerection in all animals
 Black discolored faeces in all animals
 Reduced defecation in all animals
 Exsiccosis in all animals
 Macroscopic pathological findings in the animals that died:
o Filled stomach with blackish liquid, discoloration of the stomach contents
o Dark discolored small and large intestine

500 mg/kg (both test groups):
 No clinical signs were observed

The body weights of the surviving animals in both 500 mg/kg bw test groups increased within the normal range throughout the study period.
There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (6 females of both 500 mg/kg bw test groups).
The acute oral LD50 was calculated to be
LD50, oral, rat > 500 < 2000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study the median lethal dose of KDLNO after oral administration was found to be greater than 500 mg/kg bw and less than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, doses of 2000 and 500 mg/kg bw of the test item KDLNO (preparations in corn oil Ph.Eur.) were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females, 500 mg/kg bw in 6 females).

 

Under the conditions of this study the median lethal dose of KDLNO after oral administration was found to be greater than 500 mg/kg bw and less than 2000 mg/kg bw in rats. The acute oral LD50 was calculated to be LD50, oral, rat > 500 < 2000 mg/kg bw