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

Endpoint summary

Description of key information

Oral:

LD50 > 2000 mg/kg bw (rat, OECD 423 (limit), GLP, K1)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 Dec 2001

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

Dec 2002

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

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

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- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.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

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)

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

Acute oral toxicity:

In an acute oral toxicity study according to OECD TG 423 and GLP, a total of 6 female fasted rats (2 groups with 3 animals each; 9-10 weeks of age; Wistar) were given a single oral dose of a suspension of test substance in corn oil as gavage at a dose level of 2000 mg/kg body weight followed by a 14 days observation period. No mortalities occurred. Impaired general state and piloerection was observed in two animals each. All animals gained weight in a normal range throughout the study period. In gross necropsy, there were no macroscopic pathological finding. Overall, under the chosen test conditions, the test substance was not toxic after single oral administration: oral LD50 > 2000 mg/kg bw

 

Since the registered substance Alkaline co-precipitation products of soluble cobalt, manganese and nickel salts and the different constituents of the UVCB release the same toxicological relevant unit under physiological relevant conditions, the overall toxicity of dissolved nickel, cobalt and manganese ions can be used to assess the toxicity of the registered substance for endpoints where substance specific data is not required for a registration as transported isolated intermediate >1000 t/a according to Annex VII of REACH regulation.

In the absence of substance specific information data from Nickel dihydroxide, Cobalt dihydroxide, Tricobalt tetraoxide, Trimanganese tetraoxide and Manganese dioxide are used for hazard assessment based on a worst-case mixture approach.

Nickel dihydroxide is classified for acute oral toxicity as Acute Tox. 4 (H302) and for acute inhalation toxicity as Acute Tox. 4 (H332) under the 1st ATP to the CLP. Nickel dihydroxide is not classified for acute dermal toxicity according to the 1st ATP to the CLP Regulation.

Cobalt dihydroxide is classified as Acute Tox. 4 (H302) and Acute Tox. 1 (H330) according to the classification criteria in Regulation (EC) No. 1272/2008. No data on acute dermal toxicity for Cobalt dihydroxide is available.

Based on the available data, Tricobalt tetraoxide and Trimanganese tetraoxide are not classified for acute oral and inhalation toxicity under Regulation (EC) No. 1272/2008, no data on acute dermal toxicity is available.

Manganese dioxide is classified for acute oral toxicity as Acute Tox. 4 (H302) and for acute inhalation toxicity as Acute Tox. 4 (H332) under the 1st ATP to the CLP. No data on acute dermal toxicity for Manganese dioxide is available.

The classification criteria according to Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met for Nickel dihydroxide, Cobalt dihydroxide, Tricobalt tetraoxide, Trimanganese tetraoxide and Manganese dioxide.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No. 1272/2008. Based on substance specific data, the registered substance is not classified for acute oral toxicity.

In the absence of substance specific information data from Nickel dihydroxide, Cobalt dihydroxide, Tricobalt tetraoxide, Trimanganese tetraoxide and Manganese dioxide are used for hazard assessment based on a worst-case mixture approach.

Based on the mixture approach, the registered substance is not classified for acute inhalation toxicity under Regulation (EC) No. 1272/2008. No data on acute dermal toxicity is available.