Olivine, cobalt silicate blue

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-10-30 to 2019-11-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

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:

2001-12-17

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008-05-31

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2017-05-08

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Olivine, cobalt silicate blue

EC Number:

269-093-5

EC Name:

Olivine, cobalt silicate blue

Cas Number:

68187-40-6

Molecular formula:

Co2SiO4

IUPAC Name:

silicon(4+) bis(λ²-cobalt(2+)) tetraoxidandiide

Test material form:

solid: particulate/powder

Details on test material:

- Test item identification: Olivine, cobalt silicate blue (Pigment Blue 73)
- Substance type: inorganic pigment
- Storage condition of test material: Keep dry and container tightly closed. Keep container in an adequately ventilated storage

Test animals

Species:

rat

Strain:

other: CD/Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 54 days
- Weight at study initiation: 186 - 220 g
- Fasting period before study: Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum. After administration, food was withheld for approx. 3 hours.
- Housing: during the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. The cages were changed and cleaned twice a week.
- Diet: ad libitum, commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water: ad libitum, drinking water in bottles
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C (maximum range)
- Humidity: 55 ± 10% (maximum range)
- Air changes: 15 to 20 times per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 2019-10-30 To: 2019-11-18

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous hydroxypropyl methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg bw
- Amount of vehicle: 1.9 - 2.2 mL
- Justification for choice of vehicle: 0.8% aqueous hydroxypropylmethylcellulose was chosen as inert vehicle as it is known not to produce any toxic effects and revealed a homogenous and stable suspension of the test item for application in the organism of the animals.
- Batch no.: DTR459964
- Source: Colorcon GmbH, 65510 Idstein, Germany

MAXIMUM DOSE VOLUME APPLIED: 10 mg/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Following administration, observations were made and recorded systematically with individual records being maintained for each animal. Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration.
- Necropsy of survivors performed: yes, at the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded.

- Other examinations performed: During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Observations on prematurely deceased animals were made at least once daily to minimize loss of animals during the study. The time of death would have been recorded as precisely as possible. Individual body weights were recorded shortly before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded when survival exceeded one day. No histopathology was carried out as no macroscopical findings were noted at autopsy.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality could be observed.

Clinical signs:

other: No clinical signs were noted.

Gross pathology:

No pathological changes were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A single oral administration of Cobalt silicate olivine (Pigment blue 73)/kg b.w. did not reveal any signs of toxicity in any of the 6 animals. The LD50 value for female rats is >2000 mg Cobalt silicate olivine (Pigment blue 73)/kg bw.
According to the EC Regulation 1272/2008 and subsequent regulations, the test item does not require classification for acute oral toxicity.
According to the Globally Harmonized Classification System (GHS) the test item requires no labelling for acute oral toxicity (as LD50 > 2000 mg/kg b.w.).

Executive summary:

Cobalt silicate olivine (Pigment blue 73) was examined for acute toxicity after a single oral administration to rats (acute toxic class method). The test substance was suspended in 0.8 aqueous hydroxypropyl methylcellulose and administered via gavage to 6 female rats. Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All animals were observed for a period of 14 days. Individual body weights were recorded shortly before administration of the test item and thereafter in weekly intervals up to the end of the study. At the end of the study, all animals were necropsied. No histopathology was carried out.

Under the present test conditions, a single oral administration of 2000 mg Cobalt silicate olivine (Pigment blue 73)/kg b.w. did not reveal any signs of toxicity in any of the 6 animals. All animals gained the expected body weight. No pathological changes were observed at necropsy.

The LD₅₀value was ranked exceeding 2000 mg/kg bw.