Alkaline co-precipitation products of soluble cobalt, manganese and nickel salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29-Nov-2021 to 21-Dec-2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

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:

17 Dec 2001

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

Dec 2002

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147,

Version / remarks:

24 Nov 2000
as this in line with OECD 423

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Alkaline co-precipitation products of soluble cobalt, manganese and nickel salts

Molecular formula:

Co(OH)2(0.005-0.1)Co2O3(0.03-0.3)Mn3O4(0.01-0.1)MnO2(0.02-0.25)Ni(OH)2(0.35-0.91) The stoichiometry of (OH)x+Oy per metal component in the substance cannot be determined unambiguously from solely analytical data, since the composition of the present UVCB substance is highly variable (i.e. complexly mixed and poorly ordered at the atomic level). The composition of the UVCB substance can be estimated based on analytical examination in combination with a calculation that is based on the average oxidation number (NOx) in the sum of the elements Ni, Co, Mn. As a result, the following constituents in concentration ranges as described below can be identified in the UVCB: The sum of all constituents equals 1 and ranges are: • Co(OH)2: 0.005-0.1 • Co2O3: 0.03-0.3 • Mn3O4: 0.01-0.1 • MnO2: 0.02-0.25 • Ni(OH)2: 0.35-0.91

IUPAC Name:

Alkaline co-precipitation products of soluble cobalt, manganese and nickel salts

Test material form:

solid

Specific details on test material used for the study:

Purity: 100 % (UVCB) (for details see analytical report No.: 21L00179)
Homogeneity: The test item was homogeneous by visual inspection.
Storage stability: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
Expiry date: April 26, 2023
Storage conditions: Room temperature
Physical state/ color: Solid / black

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han) SPF

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Supplier: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adult animals (approx. 9 – 10 weeks)
- Weight at study initiation: animals of comparable weight (± 20% of the mean weight, 169-175 g)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Makrolon cage, type III; single housing
- Historical data: not applicable
- Diet (e.g. ad libitum): LASQCdiet® Rod16, HiHyg, LASvendi (Altromin, 32791 Lage, Germany)
- Water (e.g. ad libitum): Tap water
- Acclimation period: at least 5 days before administration
- Microbiological status when known: SPF
- Method of randomisation in assigning animals to test and control groups: not applicable, since acute toxicity testing as limit test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30-70 %
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

IN-LIFE DATES: From: 29-Nov-2021 To: 21-Dec-2021

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40 g test substance / 100 ml corn oil
- Justification for choice of vehicle: Good homogeneity in corn oil Ph. Eur.
- Purity: Ph.Eur.

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw

DOSAGE PREPARATION: The test item was prepared for each test group shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer.

CLASS METHOD:
- Rationale for the selection of the starting dose: By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals.
Because no mortality occurred, a further dose of 2000 mg/kg bw was administered to another group of 3 female animals in the second step. The sponsor requested a starting dose of 2000 mg/kg bw since no acute oral toxicity was to be expected.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A check for any dead or moribund animals was made at least once each workday; individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation
- Necropsy of survivors performed: yes; necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation. No histological examinations were performed.
- Clinical signs including body weight: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter; individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation
- Other examinations performed: no

Statistics:

not applicable (means, standard deviations, etc. were calculated with Microsoft Excel and a calculator)

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: impaired general state and piloerection

Body weight:

other body weight observations

Remarks:

All animals gained weight in a normal range throughout the study period

Gross pathology:

There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period.

Other findings:

No other findings

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after oral administration was assessed to be greater than 2000 mg/kg bw in female Wistar rats.