Tricobalt bis(orthophosphate)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from October 22, 1998 to February 11, 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

version February 24, 1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

version August 1998

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tricobalt bis(orthophosphate)

EC Number:

236-655-6

EC Name:

Tricobalt bis(orthophosphate)

Cas Number:

13455-36-2

Molecular formula:

Co3(PO4)2

IUPAC Name:

tricobalt bis(orthophosphate)

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Young adult albino rats of the CrL:CD(SB)BR strain
- Source: Charle River Laboratories,Inc., Protage, Michigan on October 19 and 26 and November 9, 1998
- Acclimatisation period: At least 7 days
- Housing: group caging by sex
- Cage type: Suspended, stainless steel cages
- Diet: Continuous access to Rodent Diet #8604 (Harlan Teklad) and water except for 17 to 20 hours before test material administration when the diet, not water, was withheld. The diet is routinely analized by the manufacturer for nutritional components and environmental contaminants. Samples of water are periodically analyzed. There were no known contaminants in the diet or water at levels that would be expected to interfere with or affect the results of the study.
- Sex: Male and female healthy
- Age of animals at dosing: Approximately 8 to 12 weeks of age
- Body weight range at dosing: 201-269 g
- Identificaiton: by animal number and corresponding ear tag throughout the study

ENVIRONMENTAL CONDITIONS
- Lighting period: 12 hours light/12-hour dark cycle
- Temperature: 18 - 26°C
- Relative humidity: 30 - 70 %

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled water

Details on oral exposure:

The test material was mixed with distilled water to a specific concentration for each dose level. Each prepared test material mixture appeared to be a suspension. An individual dose of each respective test materail mixutre was calculated for each animal based on its fasted body weight and administered as a single gavage dose at a volume of 5mL/kg of body weight. The test material mixtures were stored at room temperature until adminsitered.

Doses:

1000, 1500 and 2000 mg/kg

No. of animals per sex per dose:

5 females and 5 males per dose

Control animals:

no

Details on study design:

Initially, a single dose of 1000 mg/lg was administered to five males and five females. Based on the results of this initial dose level, additonal dose levels were added at the direction of the study director in oder to meet the objectives of the study: 1500 mg/kg, then 2000 mg/kg.

Clinical observations were conducted at 1, 2.5 and 4 hours after test material administration and daily thereafter for 14 days. Mortality checks were conducted twice a day (morning and afternoon) for 133 days after test material administration and again the morning of Day 14.

Body weights were determined before test material adminsitration (Day 0). Additional body weights ware determined Day 7, at termination of the respective in-life phase (Day 14), or at death when survival exceeded the day of treatment.

At termination of the respective in-life phase for each dose level, surviving animals were euthanized. All animals, whether found dead during the study or euthanized, were subjected to a macroscopic necropsy examinaiton and any abnormalities were recorded. After necropsy, the animals were discarded and no tissues saved.

Statistics:

Usinf the mortalities values observed during the study, the estimated LD50 values for females and the sexes combined were determined by a computer program using modified Behrens-Reed-Muench cumulant method. No other statistical evaluations were required by the protocol.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 851 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 538 - <= 2 228

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 651 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 210 - <= 2 252

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One female animal treated at 1000 mg/kg ws found dead within 3 days of test material administration. Two female animals treated at 1500 mg/kg were found dead within 4 days of test material administration. Two males and three females treated at 2000 mg/kg were found dead within 4 days of test material administration.

Clinical signs:

other: other: red stained face, black or liquid faces, drak stained urogenital area, thin appearance, hunched posture, death.

Gross pathology:

At necropsy, most changes observed were in the animals that died and the more prominent observations pertained to the content of the gastrointestinal tract. In most of these animals given 1500 or 2000 mg/kg, the stomach and intestines were observed to contain dark fluid or semisolid material described variably being black or tan and purple. This content possibly represented test material mixed with ingesta. Some of these animals also had black material (staining) in the haircoat of the perianal or perineal regions, or the haircoat of the entire ventral surface. All remaining observations were considered incidental findings and unrelated to the test material.

Any other information on results incl. tables

CLINICAL SIGNS DESCRIPTION:

Clinical signs of toxicity were observed in one male and three femals treated at 1000 mg/kg and included red stained face, black or liquid feces, dark stained urogenital area, thin appearance and death. The surviving animals treated at this dose level returned to a normal appearance by Day 7 after treatment.

All animal treated at 1500 mg/kg appeared normal troughout the study with the exception of two females which were found dead on Day 4.

Clinical signs of toxicity observed at the 2000 mg/kg dose level included red stained face, liquid black feces, thin appearance, hunched posture and death. The surviving animals treated at this dose level returned to a normal appearance by Day 6 after treatment.

BODY WEIGHTS:

Animals surviving till the end of the observation period exhibited body weight gain during the study with the exception of one female at 1000 mg/kg which exhibited an insignificant wieght loss of 9g during the second week.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the mortality observed in the study conducted in accordance with O.E.C.D. test guideline n° 401, the estimated oral LD50 values of the test item in rats were determined to be:
- greater than 2000 mg/kg for males,
- 1651 mg/kg for females, and
- 1851 mg/kg for the sexes combined.
According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the Regulation EC n°1272/2008, the test item has to be classified in category 4. The signal word 'Warning' and hazard statement H302 'Harmful if swallowed' are required.