Molybdenum zinc tetraoxide

Endpoint summary

Description of key information

Acute oral toxicity: Key study: OECD 423. GLP study. The LD50 of the test item is greater than 2000 mg/kg body weight after single oral administration to Wistar rats. The LD50 cut off value was determined to be 2500 mg/kg body weight.

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:

06 July 2018 - 08 August 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Slovak Academy of Sciences Dobrá Voda, Slovak Republic
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 89-203g
- Fasting period before study: Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night).
- Housing: 3 animals per cage, in plastic cages suspended on stainless steel racks.
- Diet (e.g. ad libitum): Ad libitum (ssniff Spezialdiäten GmbH, Germany)
- Water (e.g. ad libitum): Ad libitum (tap water)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.96 ± 0.46 °C
- Humidity (%): 54.83 ± 2.65 %
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12-hour light /12-hour dark cycle.

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 5 mL/kg bw
- Justification for choice of vehicle: Common vehicle according to the OECD TG 423. It was chosed based on preliminary works.
- Lot/batch no. (if required): L71143

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

DOSAGE PREPARATION (if unusual): The required amount of the test item (according to the body weight and dose) was mixed with vehicle (Olive oil) shortly before administration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A limit dose of 2000 mg/kg bw was used as a starting dose (no adverse effects expected).

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females (in two steps, 3 rats per step).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs: Immediately after administration and 0.5, 1, 2, and 4 hours later. Daily for the next 14 days.
Parameters: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular attention was given to potential neurologic endpoints such as tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body weight: Immediately prior to administration and weekly thereafter.
- Necropsy of survivors performed: yes
Parameters: External appearance, the cranial, thoracic and abdominal cavities, the appearance of the tissues and organs.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Mortality:

5/6 females survived the limit dose of 2000 mg/kg body weight. Test item-related mortality was observed in one animal on the 3rd day after administration without any previous clinical symptoms.

Clinical signs:

other: During the study, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.

Gross pathology:

No macroscopic findings were observed.
Dead animal could not be necropsied because of autolysed cadaver.

Body weight:

Sex	Dose	ID	Body Weight (g)			Body Weight Difference (g)
			Initial	Week 1	Week 2	Week 1 - Initial	Week 2 - Initial	Week 2 - Week 1
♀	2000 mg/kg	1	197	184	215	-13	18	31
		2	189	195	215	6	26	20
		3	192	189	202	-3	10	13
		4	203	184	209	-19	6	25
		5	194	-	-	-	-	-
		6	203	170	203	-33	0	33

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 of the test item is greater than 2000 mg/kg body weight after single oral administration to Wistar rats. The LD50 cut off value was determined to be 2500 mg/kg body weight.

Executive summary:

An acute oral toxicity test was performed according to the OECD Guideline 423 (GLP study). The test item was administered in a single  dose of 2000 mg/kg bw by gavage. One group of 3 females was dosed. Test item-related mortality was not observed during 24 hours and therefore, in a second step, another 3 females were treated at the same dose. Animals were observed for 14 days. Individual weights of animals were measured. All test animals were subjected to gross necropsy. The test item caused death of one animal. No signs of toxicity were observed during the first 4 hours or the 14-day observation period thereafter. The body weights of all survived animals decreased during the first week after administration of the test item except one animal. No body weight losses were observed between the first and second week after administration. During necropsy, no macroscopic findings were observed. The LD50 of the test item is greater than 2000 mg/kg body weight after single oral administration to Wistar rats. The LD50 cut off value was determined to be 2500 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 500 mg/kg bw

Quality of whole database:

One study available with a Klimisch score of 1 (GLP study).

Justification for classification or non-classification

Based on the available data (LC50 > 2000 mg/kg bw), the test item is not classified for acute toxicity by oral route according to the CLP Regulation (EC) no. 1272/2008.