Dimolybdenum carbide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

In a developmental toxicity study (OECD Test Guideline 414) Sodium molybdate dihydrate (99.9%), was administered to 5 groups of 25 female Sprague Dawley rats/dose in diet. Dose levels of 0, 3, 10, 20 and 40 mg Mo/kg bw/day were administered from day 6 to day 20 of gestation. No adverse effects were observed at any dose level on the dams, or on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations. Significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed. The NOAEL for both maternal toxicity and developmental toxicity of molybdenum (given as Sodium molybdate dihydrate) in the diet was 40 mg Mo/kg bw/day.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Study period:

Not provided in publication

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The developmental toxicity study in the rat is classified acceptable; and satisfies the guideline requirement for a developmental toxicity study OECD 414 in rats under GLP. Sodium molybdate dihydrate used as read across partner to Dimolybdenum carbide.

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

not tested up to the limit dose

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Age at study initiation: 8–10 weeks of age upon arrival on gestational day (GD) 0 or 1.
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: individually in solid-bottom, polycarbonate caging, during gestation to GD 20.
- Diet (e.g. ad libitum): Certified Purina Rodent Chow 5002 (Purina Mills, Inc., Richmond, IN, USA); ad libitum
- Water (e.g. ad libitum): Tap water; ad libitum
- Acclimation period: None, arrived at RTI laboratory already pregnant considered GD1 and immediately retained for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): RH 50 ± 20%
- Air changes (per hr): 10–15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: No data provided To: No data provided

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The test substance was formulated in Certified Purina Rodent Chow 5002 (Purina Mills, Inc., Richmond, IN, USA) at RTI International at various concentrations using GLP-compliant procedures and equipment. Concentrations of Sodium molybdate dihydrate in the diet in parts per million (ppm; mg/kg feed) were prepared, based on measured intakes from a range-finding study, to provide target molybdenum intakes of 0, 3, 10, 20 and 40 mg Mo/kg bw/day. The corresponding Sodium molybdate dihydrate concentrations in the diet were 0, 100, 338, 675 and 1350 ppm, respectively.

DIET PREPARATION
- Rate of preparation of diet (frequency): Not reported
- Mixing appropriate amounts with (Type of food): Not reported
- Storage temperature of food: Not reported

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Homogeneity of the dosed feed formulations was evaluated at the lowest and highest proposed dietary concentrations. Analyses indicated that the high and low dose formulations were stable for at least 28 days at room temperature and that the dietary dose formulations of Sodium molybdate dihydrate (SMD) in the feed at 0, 100, 338, 675, and 1350 ppm (parts per million) were accurate; all dietary samples were well within ±10% of the target concentrations of molybdenum, and were homogeneous. The concentrations of test substance added to the diet of 0, 100, 338, 675, and 1350 ppm provided target molybdenum concentrations of 0, 40, 134, 268, and 536 ppm. The analyses of molybdenum in the feed samples gave actual concentrations of molybdenum of 1.75–1.80, 39.7–40.8, 134–139, 264–268, and 540–542 ppm for the 0, 40, 134, 268, and 536 ppm feeds, respectively.

Details on mating procedure:

Mated and confirmed pregnancy with vaginal smear prior to arrival to testing laboratory from Charles River Laboratory was designated GD 0.

Duration of treatment / exposure:

Administered in feed from GD6 to GD20.

Frequency of treatment:

ad libitum, 7 days/week

Duration of test:

14 days

Remarks:

Doses / Concentrations:
0 mg Mo/kg bw/day
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
3 mg Mo/kg bw/day
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
10 mg Mo/kg bw/day
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
20 mg Mo/kg bw/day
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
40 mg Mo/kg bw/day
Basis:
nominal in diet

No. of animals per sex per dose:

25

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: Concentrations of Sodium molybdate dihydrate in the diet in parts per million (ppm; mg/kg feed) were prepared, based on measured intakes from a range-finding study to provide target molybdenum intakes of 0, 3, 10, 20 and 40 mg Mo/kg bw/day. The corresponding Sodium molybdate dihydrate concentrations in the diet were 0, 100, 338, 675 and 1350 ppm, respectively.
- Rationale for animal assignment (if not random): The test animals were divided into 5 groups of 25 by stratified randomization by body weight on GD 3, to provide uniform mean body weights across dose groups (±20%).

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least once daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: At least once daily along with cage side observations. The severity and duration of the signs were recorded. Daily morbidity/mortality checks were done twice per day, at least 6 h apart, beginning the day after receipt.

BODY WEIGHT: Yes
- Time schedule for examinations: Measured on GD 3, 6, 9, 12, 15, 18, and 20, at approximately the same time in the morning each day.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, measured on GD 3, 6, 9, 12, 15, 18, and 20, at approximately the same time in the morning each day.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: Not applicable

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day GD20
- Organs examined: Uterus, liver and kidney weights were recorded, ovarian corpora lutea counts performed, and maternal gross lesions were retained in 10% formalin. Histopathological evaluation of livers and kidneys from the remaining 15 pregnant control females and from 15 pregnant high dose females were performed.

OTHER: Serum from 10 arbitrarily selected females per group, collected via cardiac puncture, livers and kidneys (2 per female) and placentae from the same 10 were analyzed for Molybdenum, manganese, iron, cobalt, copper, zinc and selenium concentrations.

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes

Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter
- Head examinations: Yes: half per litter

Statistics:

All statistical analyses were performed using ProvantisTM software. For all statistical tests, P< 0.05 was used as the criterion for significance and the dam or litter was used as the statistical unit as appropriate. Quantitative continuous data (e.g., maternal body weights and weight gains, feed consumption in g/day and g/kg body weight/day) were subjected to the Provantis generalized ANOVA/ANCOVA test. This decision tree includes analysis of variance (ANOVA) and covariance (ANCOVA), nonparametric analysis of variance, pairwise tests for parametric and nonparametric data, and Levene’s test for homogeneity of variane. For each variable analyzed, where there was evidence of differences between groups, the methodology also identified those groups, which differed from the control group for these variables. The uterine weight and uterine implant data were subjected to the Kruskal–Wallis nonparametric analysis of variance, the default technique in Provantis. When there was evidence of a significant group effect, pairwise comparisons of each treated group with the control group were performed using Dunnett’s test on the ranks. The fetal weights and sex ratios were subjected to a 1-way mixed ANOVA, the default technique in Provantis. When there was evidence of a significant group effect, pairwise comparisons of each treated group with the control group were performed using Dunnett’s test on group least square means. Statistical analyses of the Michigan State University analytical data on blood and tissue minerals were performed using Students t-test, 2 tailed, heteroskedastic compared with corresponding controls, and P < 0.01 was used as the criterion for significance.

Indices:

No data reported

Historical control data:

No data reported

Details on maternal toxic effects:

Maternal toxic effects:no effects. Remark: Significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed.

Details on maternal toxic effects:
No adverse effects were observed at any dose level on the dams; although significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed.

OBSERVATIONS / MORTALITY: There were no treatment- or dose-related maternal clinical signs in any female in any group. Of the 125 female rats in the study, only one, in the 20 mg Mo/kg bw/day dose group, was not pregnant. None of the females died during the study, and none of the pregnant females aborted or had complete resorptions at scheduled necropsy. All 25 pregnant females at 0, 3, 10, and 40 mg Mo/kg bw/day and all 24 pregnant females at 20 mg Mo/kg bw/day had live litters at scheduled termination (See Table 1 in "Any other information on results incl. tables" section below).

MATERNAL BODY WEIGHTS: Mean maternal body weights during gestation were equivalent across all groups on GD 3, 6, 9, 12, 15, 18, and 20, with no significant differences in bodyweights or bodyweight gains during treatment. The mean (±SEM) bodyweights of the groups at start of treatment on GD 6 ranged from 250 ± 2.53 g to 254 ± 2.61 g, and on GD 20 ranged from 367 ± 4.75 g to 377 ± 4.65 g with no dose related trend.

FOOD CONSUMPTION: The mean maternal feed consumption values in g/day and g/kg bw/day during gestation were also equivalent across all groups for all gestational intervals. The mean (±SEM) daily food intakes between GD 6 and GD 20 in the control, 3, 10, 20 and 40 mg Mo/kg bw/day groups were 21.2 ± 0.5, 22.0 ± 0.6, 22.7 ± 0.6,22.8 ± 0.8 and 21.0 ± 0.6 g/day, respectively.

FOOD EFFICIACY: The actual mean ± SEM molybdenum intake during GD 6–20 in the nominal target dose level groups of 3, 10, 20, and 40 mg Mo/kg bw/day was 2.8 ± 0.07; 9.8 ± 0.24; 20.0 ± 0.68; and 37.5 ± 1.0 mg Mo/kg bw/day, respectively. The molybdenum content of the control diet was 1.8 mg Mo/kg diet, and the drinking water contained 0.2 g Mo/L, giving an additional intake of 0.13 mg Mo/kg bw/day in all groups, including controls, and was not included in the above intake values.

GROSS PATHOLOGY: At scheduled necropsy on GD 20, there were no differences across groups for mean terminal body weight, gravid uterine weight, net body weight (terminal body weight minus gravid uterine weight), or for corrected mean body weight change from GD 3 to GD 20.

ORGAN WEIGHTS: Maternal terminal body weights, and absolute and relative (to terminal body weight) maternal liver and paired kidney weights were all statistically and biologically equivalent across all groups. All maternal kidneys were subjected to gross pathological examination from all females on study; one female at 40 mg Mo/kg bw/day exhibited kidney discoloration, pale, bilateral, misshapen kidneys, bilateral, and dilation, bilateral, of the renal pelvis, and one female at 40 mg Mo/kg bw/day exhibited right renal pelvis dilation (they both had live litters). All maternal livers were also subjected to gross pathological evaluation, with no visible (gross) lesions observed.

HISTOPATHOLOGY: Histopathological evaluation of maternal livers and kidneys of the 15 (of 25) dams per group not used for elemental analyses, indicated no treatment- or dose-related incidences or severities of any histopathological findings in the top dose group animals compared with the controls.

CLINICAL CHEMISTRY: Analysis of the blood serum, placentae, liver and kidneys for molybdenum and other elements were performed on 10 dams per group selected at scheduled necropsy. Of the elements measured (i.e., molybdenum, copper, manganese, iron, cobalt, zinc and selenium), only molybdenum and copper showed clear dose-related increases in levels. A summary of these results for molybdenum and copper are provided in Table 3 in the "Any other information on results incl. tables" section below. Dose-related increased copper levels in serum, kidneys, livers and placentae were variously observed across all the doses, with statistically significant increases in all at the highest dose.

Copper levels in these tissues were markedly increased at increasing levels of exposure to molybdenum. The mean copper concentration in the placentae in the controls was 21.3 g/g dry weight. Similarly, in the liver, the mean copper concentration in the control group was 12.8 g/g.

Dose descriptor:

NOAEL

Effect level:

40 other: mg Mo/kg bw/day

Based on:

element

Remarks:

Molybdenum

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No adverse effects were observed at any dose level on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations.

The maternal ovarian and uterine implantation data, fetal numbers and bodyweights (See Table 1 in "Any other information on results incl. tables" section below) indicated no treatment- or dose-related differences across groups for the numbers of ovarian corpora lutea/female, the numbers of uterine implantations/female, for pre- or post-implantation loss, litter size and fetal bodyweight. No female in any group had total litter loss / completely resorbed litter.

The mean numbers of live fetuses/female were similar in all groups with no statistically or biologically significant differences among groups. There were no differences among groups for % male fetuses/dam, for mean litter weights/dam, or for individual fetal body weights, with sexes combined or separately, by sex/dam (Table 1).

A summary of fetal defects (See Table 2 in "Any other information on results incl. tables" section below) reported no statistically significant dose-related increases in fetal malformations or variations. There was 1 externally malformed fetus each at 3 and 40 mg Mo/kg bw/day; there were 2 fetuses (from 2 litters) at 10 mg Mo/kg bw/day, and 6 fetuses (from3 litters) at 20 mg Mo/kg bw/day with head malformations, and 1, 1, 4, 2 and 1 fetuses (in 1, 1, 4, 2 and 1 litters) with skeletal malformations at 0, 3, 10, 20, and 40 mg Mo/kg bw/day, respectively. No treatment related increase in fetal visceral or skeletal variations was observed. The large numbers of fetuses with skeletal variations in all groups was anticipated from the historical control rat data from previous studies in this laboratory in this rat strain. Nasal sinus, bilateral, enlarged, classified as a head malformation, was observed in 2 fetuses (from different litters) at 10 mg Mo/kg bw/day and in 6 fetuses (from 3 litters) at 20 mg Mo/kg bw/day; there were no fetuses with head malformations at 0, 3, or 40 mg Mo/kg bw/day. Fetal skeletal defects were observed in regions of the sternebrae, ribs, thoracic vertebrae and lumbar vertebrae, with no treatment-or dose-related pattern of incidences or severities.

There were clearly no dose-related incidences of fetal malformations in any group. Dilated nasal sinus as described above is an uncommon fetal finding, and it was not considered treatment- or dose-related in this study.

Dose descriptor:

NOAEL

Effect level:

40 other: mg Mo/kg bw/day

Based on:

element

Remarks:

Molybdenum

Basis for effect level:

other: developmental toxicity

Abnormalities:

not specified

Developmental effects observed:

not specified

TABLE 1

Summary of uterine implantation data (GD20) from rats exposed to dietary Sodium molybdate dihydrate (SMD) on days 6–20 of gestation (GD6–20).
Dose group: SMD ppm in diet (mg Mo/kg bw/day)		0	100	338	675	1350
		0	3	10	20	40
Number of females with live fetuses at scheduled termination		25	25	25	24	25
Total number of corpora lutea		360	364	354	345	364
Number of corpora lutea per female	Mean	14.4	14.6	14.2	14.4	14.6
	SEM	0.5	0.6	0.4	0.4	0.5
Total number of implantations		317	322	327	319	313
Number of implantations per female	Mean	12.7	12.9	13.1	13.3	12.5
	SEM	0.5	0.3	0.3	0.4	0.4
Total number of pre-implantation losses		43	42	27	26	51
Mean % per group		11.9	11.5	7.6	7.5	14
Total number of post-implantation losses		9	10	13	14	6
Mean % per group		2.8	3.1	4	4.4	1.9
Number of live fetuses per female	Mean	12.3	12.5	12.6	12.7	12.3
	SEM	0.5	0.3	0.3	0.4	0.4
Number of live fetuses as % of implantations	%	97.2	96.9	96	95.6	98.1
Total number of live fetuses		308	312	314	305	307^a
Number of males		152	141	162	155	149
Number of females		156	171	152	150	157
Fetal weight (sexes combined) (g)	Mean	4.02	4.04	4.02	4.02	4.04
	SEM	0.06	0.05	0.04	0.07	0.07
Fetal weight (males) (g)	Mean	4.13	4.16	4.12	4.13	4.14
	SEM	0.06	0.06	0.05	0.07	0.06
Fetal weight (females) (g)	Mean	3.9	3.95	3.91	3.91	3.95
	SEM	0.06	0.05	0.04	0.06	0.08
^a  One fetus inadvertently not sexed.

TABLE 2

Occurrence of external, visceral and skeletal malformations and variations in the fetuses of rats exposed to Sodium molybdate dihydrate.
Dose group (mg Mo/kg bw/day)	0	3	10	20	40
Total number of fetuses examined	308	312	314	305	307
Total number of litters examined	25	25	25	24	25
External defects
Number of fetuses examined^a	307	312	313	303	307
Number showing malformations	0	1	0	0	1
Number of litters affected	0	1	0	0	1
Number showing variations	0	0	0	0	0
Number of litters affected	0	0	0	0	0
Fresh visceral body-only defects
Number of fetuses examined	150	151	151	152	152
Number showing malformations	0	0	0	0	0
Number of litters affected	0	0	0	0	0
Number showing variations	7	4	11	2	5
Number of litters affected	5	3	8	2	4
Bouin’s head defects
Number of fetuses examined	150	151	151	152	152
Number showing malformations	0	0	2	6	0
Number of litters affected	0	0	2	3	0
Number showing variations	0	0	0	2	1
Number of litters affected	0	0	0	1	1
Skeletal defects
Number of fetuses examined	158	161	163	153	155
Number showing malformations	1	1	4	2	1
Number of litters affected	1	1	4	2	1
Number showing variations	54	69	69	65	64
Number of litters affected	18	21	22	19	22
^a In dose groups 0, 10 and 20 mg Mo/kg bw/day, 1, 1, and 2 fetuses, respectively were not examined externally but did have visceral or skeletal examination.

TABLE 3

Summary of blood serum and tissue levels of elements, which showed significant dose related changes at terminal sacrifice of 10 dams per group.
Dose: SMD ppm in diet (mg Mo/kg bw/day)		0	100	338	675	1350
		0	3	10	20	40
Blood serum levels
Molybdenum	Mean (µg/ml)	0.024	0.68^a	2.43^a	4.87^a	10.04^a
	SD	0.003	0.42	0.86	0.98	2.2
Copper	Mean (µg/ml)	2.02	2.09	2.50^a	3.07^a	3.98^a
	SD	0.22	0.34	0.4	0.81	1.12
Placental levels
Molybdenum	Mean (µg/g dry)	0.75	3.4	15.74^a	26.35^a	54.51^a
	SD	1.53	4.02	10.2	9.12	18.06
Copper	Mean (µg/g dry)	21.3	19.1	29.2	34.2^a	50.7^a
	SD	2.71	5.34	11.8	11.3	21.9
Kidney levels
Molybdenum	Mean (µg/g dry)	1.51	5.71^a	23.0^a	38.0^a	87.1^a
	SD	0.1	2.11	9.64	14.7	15.6
Copper	Mean (µg/g dry)	42.3	44.1	52.6	63.1	118.2^a
	SD	16.1	19.1	25.4	31.5	33.3
Liver levels
Molybdenum	Mean (µg/g dry)	2.47	3.43^a	6.14^a	9.71^a	17.8^a
	SD	0.14	0.8	1.64	2.2	2.63
Copper	Mean (µg/g dry)	12.8	13	14.7^a	17	19.5^a
	SD	0.68	1.94	1.53	4.62	3.46
^a  Significant difference from controls (P < 0.01).

Conclusions:

In the developmental toxicity of Sodium molybdate dihydrate as a representative of a broad class of soluble molybdenum(VI) compounds, was given in the diet to Sprague Dawley rats in accordance with OECD Test Guideline 414. Dose levels of 0, 3, 10, 20 and 40 mg Mo/kg bw/day were administered from GD6 to GD20. No adverse effects were observed at any dose level on the dams, or on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations. Significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed. The NOAEL observed in this study was 40 mg Mo/kg bw/day, the highest dose tested.

Executive summary:

In a developmental toxicity study (OECD Test Guideline 414) Sodium molybdate dihydrate (99.9%), was administered to 5 groups of 25 female Sprague Dawley rats/dose in diet. Dose levels of 0, 3, 10, 20 and 40 mg Mo/kg bw/day were administered from day 6 to day 20 of gestation. No adverse effects were observed at any dose level on the dams, or on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations. Significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed. The NOAEL (for both maternal toxicity and developmental toxicity of molybdenum in the diet (given as Sodium molybdate dihydrate)) was 40 mg Mo/kg bw/day. The developmental toxicity study in the rat is classified as acceptable; and satisfies the guideline requirement for a developmental toxicity study OECD 414 in rats under GLP conditions.

This study was conducted at concentrations below the limit dose of 1000 mg/kg/d, and below clear parental toxicity. However, in a 90-day study by the same author (Murray 2014) a NOAEL of 17 mg Mo/kg/d (LOAEL of 60 mg Mo/kg/d) was reported. It can be assumed that maternal toxicity in an OECD 414 study (sub-acute) sets in at concentrations above 40 mg and below 180 mg Mo/kg/d (based on a 90d LOAEL of 60 mg/kg/d and a factor of 3 for extrapolating sub-chronic to sub-acute exposure). Therefore, repeating this study with slightly higher concentrations of Mo would not be considered in line with animal welfare considerations. This argument is further supported by the significant lower water solubility of Mo2C compared to Sodium molybdate.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

40 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

OECD guideline 414 study

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

No data is available for Dimolybdenum carbide (target substance). Thus, available data from Sodium molybdate dihydrate was used in a read-across approach. Due to a lower water solubility of Dimolybdenum carbide than for Sodium molybdate dihydrate the resulting toxicity potential would also be expected to be lower. Therefore, the read across to the source substance Sodium molybdate dihydrate is adequately protective. For further information please refer to the read-across report.

In a developmental toxicity study (OECD Test Guideline 414) Sodium molybdate dihydrate (99.9% a.i.), was administered to 5 groups of 25 female Sprague Dawley rats/dose in diet. Dose levels of 0, 3, 10, 20 and 40 mg Mo/kg bw/day were administered from day 6 to day 20 of gestation. No adverse effects were observed at any dose level on the dams, or on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations. The NOAEL (for both maternal toxicity and developmental toxicity of molybdenum (given as Sodium molybdate dihydrate) in the diet) was 40 mg Mo/kg bw/day. Based on the NOAEL for molybdenum the NOAEL for the target substance Dimolydenum carbide can be calculated with 43 mg/kg bw/day.

This study was conducted at concentrations below the limit dose of 1000 mg/kg/d, and below clear parental toxicity. However, in a 90-day study by the same author (Murray 2014) a NOAEL of 17 mg Mo/kg/d (LOAEL of 60 mg Mo/kg/d) was reported. It can be assumed that maternal toxicity in an OECD 414 study sets in at concentrations above 40 mg and below 180 mg Mo/kg/d (based on a 90d LOAEL of 60 mg/kg/d and a factor of 3 for extrapolating sub-chronic to sub-acute exposure). Therefore, repeating this study with slightly higher concentrations of Mo would not be considered in line with animal welfare considerations. This argument is further supported by the significant lower water solubility of Mo2C compared to Sodium molybdate.

Justification for classification or non-classification

No adverse effects were reported in a developmental toxicity study (OECD 414) in rats after treatment with Sodium molybdate dihydrate. Based on the available data the target substance Dimolybdenum carbide does not warrant classification for reproductive toxicity.