Cobalt(2+) hydrogen citrate

Endpoint summary

Description of key information

Cobalt citrate
Oral: LD50 (rat) = 500 mg/kg bw 

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:

21 Feb 2012 - 07 Mar 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted in 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Secrétariat général du GIPC - DGCIS, Services de l'industrie, bureau de la chimie, Paris, France

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Additional information on strain: SPF Caw
- Source: Elevage Janvier (53940 Le Genest St Isle, France)
- Age at study initiation: 8 weeks
- Fasting period before study: yes (food was removed on day 0 and then redistributed 4 hours post-application)
- Weight at study initiation: 196 - 212 g
- Housing: 3/cage in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid
- Diet: pelleted M20 rat/mouse maintenance diet (Extralabo from Pietrement); ad libitum
- Water: tap water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: step 1 and 2: 200 mg/mL; step 3 and 4: 30 mg/mL
- Amount of vehicle (if gavage): 10 mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw (step 1 and 2)
300 mg/kg bw (step 3 and 4)

No. of animals per sex per dose:

3 per step (females)

Control animals:

other: no concurrent control; vehicle control tested approx. 2 months before

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: day 0, 2, 7, and 14
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The LD 50 cut-off value is considered to be 500 mg/kg bw according to the OECD guideline No. 423.

Mortality:

- 2000 mg/kg bw: 6/6 animals died
(step 1: 1/3 on day 3, 2/3 on day 5; step 2: 2/3 on day 3, 1/3 on day 4)
- 300 mg/kg bw: 0/6 animals died

Clinical signs:

other: - 2000 mg/kg bw: decrease in spontaneous activity (6/6), decrease in muscle tone (1/6), decrease in righting reflex (1/6), and piloerection (4/6) (all signs from 48 hours post-treatment) - 300 mg/kg bw: No clinical signs related to the administeration of

Gross pathology:

- 2000 mg/kg bw: Due to marked signs of autolysis, the macroscopical examinations were not possible in 5/6 animals. Examination of one dead animal revealed an important thinning of the forestomach and a thinning of the corpus with black spots.
- 300 mg/kg bw: No treatment-related findings were observed.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Acute Oral 4, H302
DSD: Xn, R22

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The acute oral toxicity study has been performed according to OECD 423 (Colas, 2012). 6 female rats each received a single oral dose of 2000 mg/kg bw or 300 mg/kg bw cobalt citrate. In the lower dosed group, all animals survived and no test substance-related clinical signs were observed. Macroscopical examination of the animals did not reveal treatment-related changes.

All 6 females treated with 2000 mg/kg bw died: 3 during the first step of the study on day 3 (1/3) and on day 5 (2/3), and 3 during the second step of the study on day 3 (2/3) and on day 4 (1/3). No clinical sign was noted during the first 24 h after the treatment. From 48 h post-dose, the mortatilites were preceded by decrease in spontaneous activity (6/6), in muscle tone (1/6), and in righting reflex (1/6), and piloerection (4/6). Rigor mortis and diarrhoea were noted before the necropsy (1/6). Due to the marked signs of autolysis, the macrosopical examinations were not possible in 5 animals (5/6). The The LD50 cut-off was determined to be 500 mg/kg bw cobalt citrate.

No experimental data are available for acute toxicity following inhalation and dermal contact.

Justification for selection of acute toxicity – oral endpoint
There is only one study available.

Justification for classification or non-classification

The available data on acute oral toxicity meet the criteria for classification as Category 4, H302 according to Regulation (EC) 1272/2008 and as Xn, R22 according to Directive 67/548/EEC.

No experimental data are available for acute toxicity via the inhalation and dermal route.