Dimolybdenum carbide

Endpoint summary

Description of key information

In an acute oral toxicity study (OECD 401) young adult Crl:CD (SD) rats (5 animals per sex and dose) were orally exposed to Sodium molybdate in corn oil at concentrations of 3200, 5000 and 6400 mg/kg bw.  Mortality occured within the different dose groups. The oral LD50 for both sexes was considered to be 4233 mg/kg body weight. In an acute inhalation toxicity study equivalent to OECD 403, groups of young male and female Sprague-Dawley rats (5 per sex) were exposed via the inhalation route to Sodium Molybdate (99.7% a.i.) for 4 hours to the whole body at a mean concentration of 1.93 mg/L. No mortality or distinct clinical signs were observed after exposure to Sodium Molybdate. The LC50 for both sexes was considered to be greater than 1.93 mg/L. In an acute dermal toxicity study (OECD 402, limit test), a group of young adult Crl:CD (SD) rats (5 animals per sex) was dermally exposed to Sodium molybdate in water for 24 hours to approximately 10% of body surface area at 2000 mg/kg bw. Animals were observed for 14 days. No mortality occurred and the LD50 was considered to exceed 2000 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:

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

Adequacy of study:

key study

Study period:

1990-06-25 to 1990-11-02

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Sodium molybdate is used as read-across partner to Dimolybdenum carbide.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Crl:CD (SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Kent, England
- Age at study initiation: four to six weeks
- Weight at study initiation: 108 to 140 g
- Housing: up to five rats of the same sex in metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24-29 °C
- Humidity (%): 67%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

preliminary study: 250 and 1000 mg/kg bw
main study: 3200, 5000 and 6400 mg/kg bw

No. of animals per sex per dose:

preliminary study: 2
main study: 5

Control animals:

no

Details on study design:

- Duration of observation period following administration:
14 days
- Frequency of observations
on the day of treatment at frequent intervals for a period of 5 hours. On the subsequent days two times per day. Clinical signs were recorded at each observation.
- Frequency of weighing:
on day the day of treatment, on day 8 and day 15
- Necropsy of survivors performed: yes

Statistics:

The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney (1971, Probit Analysis).
Where the slope was not significantly different from zero, approximate confidence limits were calculated by taking the LD50 estimate given and multiplying and dividing twice by the standard error obtained after adjustment for heterogeneity.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 233 mg/kg bw

Based on:

test mat.

Mortality:

After a single oral dose of Sodium molybdate at a concentration of 3200 mg/kg bw three male and one female died within 5 hours after treatment. At 5000 mg/kg bw one male died and two female animals died within 2 days after treatment. After treatment with 6400 mg/kg bw all animals died within 2 hours after treatment.

Clinical signs:

other: Piloerection was observed in all rats within five minutes after treatment. This sign was accompanied on Day 1 and/or later intervals by: - hunched posture, waddling and pallor of the extremities in all rats dosed at 3200 and 5000 mg/kg bw , less commonly

Gross pathology:

No macroscopic abnormalities were observed

Preliminary study:

the results indicated that the acute median lethal oral dose (LD50) to male and female rats of Sodium molybdate was greater than 1000 mg/kg body weight.

Interpretation of results:

practically nontoxic

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In conclusion, the oral LD50 value in rats after treatment with Sodium molybdate was 4233 mg/kg body weight.

Executive summary:

In an acute oral toxicity study (OECD 401) young adult Crl:CD (SD) rats (5 animals per sex and dose) were orally exposed to Sodium molybdate in corn oil at concentrations of 3200, 5000 and 6400 mg/kg bw. Animals were observed for 14 days. All animals died in the high dose group. At 5000 mg/kg bw one male died and two female animals died and at 3200 mg/kg bw three male and one female died. There were treatment related clinical signs and slight changes in body weight. No treatment-related gross pathology abnormalities were observed after 14 days. Based on the mortality occured after treatment with Sodium molybdate, the oral LD50 value both in female and male Crl:CD (SD) rats was considered to be 4233 mg/kg body weight. 4233 mg sodium molybdate/kg body weight equals 2095 mg/kg body weight of the target substance Dimolydenum carbide.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 095 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

1990-04-17 to 1991-04-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study conducted equivalent to OECD guideline 403. Sodium molybdate is used as read-across partner to Dimolybdenum carbide.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, UK
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: ca. 200g
- Housing: 5 per sex per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24 °C
- Humidity (%): 35 - 65%

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
Wright dust generator
- Exposure chamber volume:
120 L
- Method of holding animals in test chamber:
cages of stainless mesh partitioned to provide 10 individual animal compartments
- Source and rate of air:
clean dried compressed air was connected to the dust generator and fow rate was 25 L/min
- Method of particle size determination:
Two samples were taken using a Marple model 296 cascade impactor.
- Temperature, humidity, pressure in air chamber:
the air temperature was measured and recorded at the start of the exposure and then at 30 min intervals during the 4-hour exposure, relative humidity was calculated from the recorded data for the water vapour content and temperature of the chamber air

TEST ATMOSPHERE
- Brief description of analytical method used:
five air samples were taken from the chamber during the exposure. Each air sample was withdrawn through a weighed glass fibre filter (Whatman GF/A) held in an open face filter holder, at a rate of 4 L/min. The volume of the air sample was measured with a wet-type gas meter. The filters were reweighed to determine the concentration of the test substance in the chamber air.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

The mean concentration of Sodium Molybdate was 1.93 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: at least two times per day for clinical signs
- Frequency of weighing: every day
- Necropsy of survivors performed: yes
- Food and water consumption: the daily mean intakes of food and water for each rat were calculated from the recorded data
- Other examinations performed:
at the end of the 14 day observation period, the rats were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear of surrounding tissue and weighed in to order to calculate the lung to body weight ratio. Lungs, Liver and Kidneys were preserved buffered 10% formalin. Fixed lungs were embedded in paraffin wax and four-micron sections were prepared, stained with haematoxylin and eosin and examined under the light microscope.

Statistics:

N.A.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.93 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no deaths during the study.

Clinical signs:

other: During exposure: Partial closing of the eyes was seen in rats exposed to Sodium Molybdate. This sign is considered to be consistent with a non-specific response to exposure to high concentration of dust. During the observation period: No signs of toxicity

Body weight:

Small losses in body weight or a reduced rate of body weight gain were observed in rats exposed to Sodium Molybdate for up to three days after exposure. Subsequently the rate of body weight gain of the exposed rats was similar to that of the control rats.

Gross pathology:

Macroscopic pathology:
The lungs of two control rats had dark areas on the surface of the lungs and the lungs of one male rat exposed to Sodium Molybdate were congested (animal 95).
Microscopic pathology:
No changes considered to be of toxicological significance were observed in the lung sections examined.

Other findings:

Food consumption:
Food consumption was reduced for two days following exposure to Sodium Molybdate. Subsequently, food consumption for exposed rats was similarto that for control rats.

Water consumption:
Water consumption was increased on Day 3 of the observation period and also, in male rats only, on day 4 after exposure.

Lung to body weight ratio:
The lung weight for one male rat (animal 95) exposed to Sodium Molybdate was higher than normal. The ratio was considered to be within normal limits for all other rats.

Table 1: Concentrations of Sodium Molybdate
Sample	Time	Test Item in air (mg/L)
2.1	0h : 30 min	2.01
2.2	1h : 00 min	1.85
2.3	2h : 00 min	1.94
2.4	3h : 00 min	1.93
2.5	3h : 50 min	1.91
	mean	1.93

Variation: 8%

Table 2: Particle Size Distribution
Sample	Time taken	Stage		Particle size range (µm)	Amount collected (mg)	% of total	% respirable (< 3.5 µm a.d.)
PSD1	1h : 40 min	3		9.80	0.37	42.50	31.00%
		4		6.00	0.09	10.30
		5		3.50	0.14	16.10
		6		1.55	0.27	31.00
		7		0.93	0.00	0.00
		8		0.52	0.00	0.00
		Filter		0.00	0.00	0.00
PSD2	3h : 30 min	3		9.80	0.34	30.60	20.70%
		4		6.00	0.31	27.90
		5		3.50	0.23	20.70
		6		1.55	0.23	20.70
		7		0.93	0.00	0.00
		8		0.52	0.00	0.00
		Filter		0.00	0.00	0.00
mass median aerodynamic diameter: 6.9 µm; standard geometric diviation: 2.71

Interpretation of results:

practically nontoxic

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In conclusion, under the conditions of the test, the LC50 of Sodium Molybdate is greater than 1.93 mg/L

Executive summary:

In an acute inhalation toxicity study equivalent to OECD 403, groups of young male and female Sprague-Dawley rats (5 per sex) were exposed by inhalation route to Sodium Molybdate (99.7% a.i.) for 4 hours to the whole body at a mean concentration of 1.93 mg/L. Animals then were observed for 14 days. No mortality or distinct clinical signs were observed after exposure to Sodium Molybdate. Since no mortality occured during the 14 -day observation period, the LC50 for both sexes is greater than 1.93 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

1990-06-13 to 1990-11-01

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Sodium molybdate is used as read-across partner to Dimolybdenum carbide.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD (SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Kent, England
- Age at study initiation: seven to ten weeks
- Weight at study initiation: 216 to 262 g
- Housing: individually in metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24 °C
- Humidity (%): 60%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10% of the total body surface ( 50 x 50 mm)
- Type of wrap if used: gauze, which was held in place with an impermeable dressing encircled firmlay around the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with 30-40 °C warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.12 ml/kg
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration:
14 days
- Frequency of observations:
on the day of treatment at frequent intervals for a period of 4 hours. On the subsequent days two times per day. Clinical signs were recorded at each observation. The treated areas of skin were examined daily for signs of dermal irritation and were assessed according to the following scoring systempresented in table 1
- Frequency of weighing:
on day the day of treatment, on day 8 and day 15
- Necropsy of survivors performed: yes

Preliminary study:

N:A:

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths following a single dermal dose of 2000 mg/kg bw

Clinical signs:

other: There were no signs of systemic reaction to treatment

Gross pathology:

Terminal autopsy revelaed no macroscopic abnormalities

Other findings:

N.A.

Interpretation of results:

practically nontoxic

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In conclusion, the dermal LD50 value in rats after treatment with Sodium molybdate was established to exceed 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study (OECD 402, limit test), a group of young adult Crl:CD (SD) rats (5 males and 5 females) was dermally exposed to Sodium molybdate in water for 24 hours to approximately 10% of body surface area at 2000 mg/kg bw. Animals were observed for 14 days. No mortality occurred. There were no treatment related clinical signs, necropsy findings or changes in body weight. The dermal LD50 value of Sodium molybdate in both female and male Crl:CD (SD) rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

No data is available for Dimolybdenum carbide (target substance). Thus, available data from Sodium molybdate was used in a read-across approach. Due to a lower water solubility of Dimolybdenum carbide compared to Sodium molybdate the resulting bioavailability (toxicity potential) would also be expected to be lower. Therefore, the read across to the source substance Sodium molybdate is adequately protective. Details on the read-across rational are provided in section 13.

In an acute oral toxicity study (OECD 401) young adult Crl:CD (SD) rats (5 animals per sex and dose) were orally exposed to Sodium molybdate in corn oil at concentrations of 3200, 5000 and 6400 mg/kg bw. Mortality occurred within the different dose groups. The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney (1971, Probit Analysis). The oral LD50 for both sexes was calculated to be 4233 mg/kg body weight. In an acute inhalation toxicity study equivalent to OECD 403, groups of young male and female Sprague-Dawley rats (5 per sex) were exposed via the inhalation route to Sodium molybdate (99.7%) for 4 hours to the whole body at a mean concentration of 1.93 mg/L (higher concentrations technically not possible). No mortality or distinct clinical signs were observed after exposure to Sodium molybdate. The LC50 for both sexes was considered to be greater than 1.93 mg/L. In an acute dermal toxicity study (OECD 402, limit test), a group of young adult Crl:CD (SD) rats (5 animals per sex) was dermally exposed to Sodium molybdate in water for 24 hours to approximately 10% of body surface area at 2000 mg/kg bw. Animals were observed for 14 days. No mortality occurred and the LD50 was considered to exceed 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint

GLP guideline study according to OECD 401. Mortality in rat was reported after treatment with 3200 mg Sodium molybdate and above. An LD50 of 4233 mg/kg/d was established (equal to 2095 mg Mo2C/kg body weight).

Justification for selection of acute toxicity – inhalation endpoint

GLP study equivalent to OECD 403 conducted with Sodium molybdate.

Justification for selection of acute toxicity – dermal endpoint

GLP guideline study according to OECD 402 conducted with Sodium molybdate.

Justification for classification or non-classification

Based on the available data Dimolybdenum carbide does not warrant classification for acute toxicity. LD50 values for the dermal and oral route are above the limit values of the relevant OECD guidelines. The LC50 value received from an acute inhalation study was greater than 1.93 mg/L (as Sodium molybdate).