Cobalt molybdate

Endpoint summary

Description of key information

Oral (OECD 423), rat: LD50: 2500 mg/kg bw (cut-off value)
Read-across from molybdenum substances: 
Inhalation (OECD 403), rat: LD50 > the maximum attainable test concentration or > 5 mg/L air (RA from soluble molybdenum substances; limit tests)
Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (RA from soluble molybdenum substances; limit tests)

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 Mar - 27 Apr 2011

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)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

Secrétariat général du Groupe Interministeriel Des Produits Chimiques - DGCIS-SI - 12, rue Villiot, 75572 Paris cedex 12, France

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle - France)
- Age at study initiation: 8 weeks
- Weight at study initiation: 180 - 201 g
- Fasting period before study: Food was removed at D-1 and then redistributed 4 h after test item administration
- Housing: by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid; each cage contains sawdust bedding which was changed at least 2 times a week; each cage was installed in conventional air conditioned animal husbandry.
- Diet: ad libitum; M20-rat/mouse maintenance (made from the formulation EXTRALABO from PIETREMENT)
- Water: ad libitum; tap water from public distribution system (microbiological and chemical analyses carried out every six months by the IPL, Santé, Environnement Durables - Atlantique)
- 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 (19:00 to 7:00)/(7:00-19:00)

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw

DOSAGE PREPARATION:
In the first and second steps of the study, 300 mg of the test item was weighed and distilled water was added to a 10 mL volumetric flask. The preparation was magnetically stirred to obtain a battle-grey solution, just before the administration.
In the third and fourth steps of the study, 2000 mg of the test item was weighed and distilled water was added to 10 mL volumetric flask. The preparation was magnetically stirred to obtain a battle-grey solution, just before the administration.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

6 (3 animals each in two steps)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were carried out daily; body weights were determined on D0 (just before administering the test substance), D2, D7 and D14
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

300 mg/kg bw dose group: no mortality (0/6)
2000 mg/kg bw dose group: death of one rat during the second step of the study on Day 6 (1/6)

2000 mg/kg bw
2 of 6 animals found dead during the study: one animal from step 1 died at 28 hours 55 minutes post-dose and one animal from step 2 died at 21 hours post-dose.

Clinical signs:

other: 300 mg/kg bw dose group: no clinical signs related to the administration of the test item were observed. 2000 mg/kg bw dose group: animal found dead (1/6): a decrease in spontaneous activity and piloerection on Day 5 surviving animals (5/6): a decrease i

Gross pathology:

300 mg/kg bw dose group: The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.
2000 mg/kg bw dose group:
animal found dead (1/6): The macroscopical examination of the dead animal revealed a thinning of forestomach and corpus; a red thickening of the distal part of the forestomach and red/greenish coloration of corpus, black liquid in the caecum and bright red coloration of the lungs.
surviving animals (5/6): The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Table 1 

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Females
300	0/0/6	---	---	0
2000	1/2/6	Day 5 – Day 6	Day 6	16.7
LD50 = 2500 mg/kg bw (LD50 cut off-according to OECD 423)

* first number = number of dead animals                                   

 second number = number of animals with clinical signs           

 third number = number of animals used                                 

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Additional information

The acute oral toxicity study has been performed according to OECD 423 (Colas, 2011). 6 female rats each received a single oral dose of 2000 mg/kg bw or 300 mg/kg bw cobalt molybdenum oxide. 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. One rat treated with 2000 mg/kg bw died on day 6. The day before, a decrease in spontaneous activity, piloerection and body weight was observed. The macroscopical examination of the dead animal revealed a thinning of forestomach and corpus; a red thickening of the distal part of the forestomach and red/greenish coloration of corpus, black liquid in the caecum and bright red coloration of the lungs. 1/5 of the surviving animals showed a decrease in spontaneous activity and piloerection, which appeared on days 5 and 6. The animal recovered a normal behaviour on day 7. The macroscopical examination of the surviving animals did not reveal treatment-related changes at the end of the study. The LD50 cut-off was determined as 2500 mg/kg bw cobalt molybdenum oxide.

 

There are no data available on acute toxicity via the inhalation or dermal route for cobalt molybdenum oxide. However, there are reliable data for soluble cobalt and molybdenum substances considered suitable for read-across using the analogue approach. For identifying hazardous properties of cobalt molybdenum oxide, the existing forms of cobalt molybdenum oxide at very acidic and physiological pH conditions are relevant for risk assessment of human health effects. Cobalt molybdenum oxide is a metal-organic salt, which is highly water soluble (~ 508 mg/L) and nearly completely dissociates in aqueous solutions. As it is expected that cobalt molybdenum oxide is capable of forming ions at very acidic and physiological pH conditions, cobalt cations and molybdate anions will be present and completely bioavailable, same as for other soluble cobalt and molybdenum compounds. Due to the existing cobalt and molybdate ions, data from other soluble cobalt and molybdenum substances are used in the derivation of toxicological endpoints for cobalt molybdenum oxide. For further details refer to the analogue justification.

 

Acute inhalation toxicity

Cobalt substances

There are no available data on acute inhalation toxicity of soluble cobalt substances.

Based on long-term inhalation studies (NTP, 1998; Bucher, 1991) conducted with the surrogate substance cobalt sulfate heptahydrate, there is clear evidence of adverse effects on the respiratory tract (see repeated dose toxicity and carcinogenicity). As cobalt molybdenum oxide contains approx. 67% particles with a particle size below 114 µM and 15% particles with a particle size below 10 µm, there is a potential risk for inhalation exposure.

However, since cobalt molybdenum oxide is classified as carcinogenic via the inhalation route (DSD: Carcinogenicity category 2; R49; CLP: Carcinogenicity category 1B; H350), the test substance is only manufactured and/or used in closed systems under strictly controlled conditions having no risk potential for exposure. In addition, general risk management measures (RMMs) and operational conditions (OCs) including personal protection equipment (PPE) are implemented to avoid the occurrence of human health effects based on the classification as carcinogenic via the inhalation exposure route.

No acute inhalation test was performed due to animal welfare considerations. This is in accordance with Regulation (EC) 1907/2006, which specifies that unnecessary tests should be avoided in terms of animal welfare.

Molybdenum substances

In acute inhalation toxicity studies covering the soluble molybdenum substances disodium molybdate and diammonium dimolybdate and the moderately molybdenum substance molybdenum trioxide, there was a complete absence of mortalities in all studies carried out according to OECD 403 (Leuschner, 2010; Jackson et al., 1991). Correspondingly, the LC50 (4h) for all tested substances was either above the maximum attainable test concentration or above the limit test concentration (> 5 mg/L air).

Acute dermal toxicity

Cobalt substances

There are no available data on acute dermal toxicity of soluble cobalt substances. Data on dermal absorption of soluble cobalt substances indicate that the in-vivo dermal absorption rate in guinea pigs is in the same range as the in-vitro dermal absorption rate reported for humans (Wahlberg, 1965). Based on these data, it was concluded that dermal exposure to cobalt(II)chloride may result in significant systemic uptake of cobalt. However, since cobalt molybdenum oxide is classified as skin sensitizer (DSD: R43; CLP: Category 1; H317), personal protectionmeasures must be applied to avoid skin contact.

No acute dermal test was performed due to animal welfare considerations. This is in accordance with Regulation (EC) 1907/2006, which specifies that unnecessary tests should be avoided in terms of animal welfare.

Molybdenum substances

For the soluble molybdenum substances molybdenum trioxide, disodium molybdate and diammonium dimolybdate, the dermal LD50 was determined to be larger than the limit test dose of 2000 mg/kg bw (Baldrick and Healing, 1990). Soluble molybdate species have a poor rate of dermal absorption (ca. 0.2%).

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.