Cobalt trihydroxide

Endpoint summary

Description of key information

Acute oral toxicity:
LD50(rat)> 5000 mg/kg bw
Acute toxicity, dermal:
Conduct of an acute dermal toxicity study is unjustified since dermal uptake is considered negligible (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2010-08-23 to 2010-09-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study reliable without restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 176-205 g
- Fasting period before study: Naive rats were fasted overnight.
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 1996). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Purina Rodent Chow # 5012; feed was replaced approx. 3-4 hours after dosing.
- Water (ad libitum): Filtered tap water
- Acclimation period: 8-21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 47-77; humidity was above the targeted upper limit for one day during the study. A portable dehumidifier was used to lower the humidity levels during this time.
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The test substance was administered as a 60% w/w mixture in distilled water.
- Justification for choice of vehicle: Preliminary solubility test conducted by EPSL indicated that mixtures in excess of 60% (i.e., 70% or 80%) were too viscous to be administered properly.

MAXIMUM DOSE VOLUME APPLIED:
5,000 mg/kg

DOSAGE:
Individual doses were calculated based on the initial body weights, taking into account the specific gravity (determined by EPSL) and concentration of the test mixture.

Based on a limit dose of 5,000 mg/kg, at the request of the sponsor, a Main test was conducted using a default starting dose level of 175 mg/kg administered to one healthy female rat and following the Up and Down procedure, five additional females were dosed.

Doses:

175, 550, 1,750 or 5,000 mg/kg bw

No. of animals per sex per dose:

1 animal per 175 mg/kg dose level
1 animal per 550 mg/kg dose level
1 animals per 1,750 mg/kg dose level
3 animals per 5,000 mg/kg dose level

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for mortality, signs of gross toxicity and behavioral changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing. Individual body weights were recorded prior to administration (initial) and again on Days 7 and 14 (termination) following dosing.
- Necropsy of survivors performed: yes; all rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Other examinations performed: Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observations of tremors, convulsions, salivation, diarrhea and coma.

Statistics:

The Acute Oral Toxicity (Guideline 425) Statistical Program (Westat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals of the 175, 550, 1750 and 5000 mg/kg dose levels survived the test substance administration.

Clinical signs:

other: All animals of the 175, 550, 1750 and 5000 mg/kg dose levels appeared active and healthy during the study; no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour were noted.

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-days observation period.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute oral LD50 of Cobalt Oxide Hdyroxide is estimated to be greater than 5,000 mg/kg in female rats.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Read-across for acute toxicity of cobalt trihydroxide is applied from the analogous substance cobalt oxide hydroxide:

- both substances show a similar water solubility and in vitro bioaccessibility (see section 4.8 and 7.1 of the respective cobalt IUCLID)

- both substances are oxide/hydroxides of cobalt in the trivalent oxidation

- cobalt oxide hydroxide is formed when cobalt trihydroxide is dried/heated, thus cobalt trihydroxide is the precursor of cobalt oxide hydroxide

Based on the above given arguments read-across is considered justified without restriction (in accordance with regulation (EC) 1907/2006, Annex XI, section 1.5).

Acute oral toxicity

The reference Durando (2011) is considered as the key study for acute oral toxicity of cobalt hydroxide oxide and will be used for classification. Female Sprague-Dawley rats were dosed a maximum of 5000 mg/kg orally via gavage. During the observation period of 14 days no adverse effects or mortalities were observed, thus the LD50 is > 5000 mg cobalt hydroxide oxide/kg bw.

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE is above 2000 mg/kg body-weight, hence no classification required.

Acute dermal toxicity

Conduct of an acute dermal toxicity study is unjustified since dermal uptake is considered negligible.

Justification for selection of acute toxicity – oral endpoint
Key study