Experimental Studies of Molybdenum Physiology and Toxicity
Molybdenum trioxide, molybdenum disulfide and molybdates
Toxicity studies of molybdenum trioxide, ammonium and calcium molybdates and molybdenum disulfide were carried out with rats and guinea pigs by the U.S. Public Health Service [Fairhall, 1945] Molybdenum trioxide and the molybdates when fed in large daily doses of from 1200 to 6000 mg Mo/kg body weight invariably proved fatal. Fatalities were few at doses of 120 to 600 mg. There were no fatalities with molybdenum disulfide. The highest dose corresponds to 420g for a 70 kg human being. In inhalation experiments (5 mg Mo/cu. ft. air) molybdenum trioxide and ammonium dimolybdate were injurious but molybdenum disulfide was much less so. Fumes of molybdenum trioxide produced by arcing across molybdenum electrodes were less toxic than molybdenum trioxide powder apparently because the rate of solution of the fume is greater on account of its small particle size (1.55 um) than that of the powder (15.6 um). So the fume is rapidly dissolved in the lungs and carried away from the site of deposition. Molybdenum trioxide and the molybdates also produced toxic effects when administered orally and by intraperitoneal injection in large doses (400 to 800 mg/kg).
Fairhall, L. T., Dunn, R. C., Sharpless, N. E. and Pritchard, E. A., The Toxicity of Molybdenum, U. S. Public Health Service, Public Health Bulletin, 1945, 293.
In a series of tests with rats and rabbits it was found that calcium, strontium, and zinc molybdates were nontoxic with respect to oral administration, skin absorption and skin irritation, and except for calcium molybdate, eye irritation [Climax Molybdenum Test]. Ammonium molybdate was toxic by oral administration and was also an eye irritant.
Climax Molybdenum Co.Test by Scientific Associates and New Drug Institute.
Toxicity data on molybdenum compounds are summarised in the Table. The low toxicity of molybdenum compounds is obvious when compared with, for example, arsenic and chromium. Ammonium molybdate is slightly toxic and molybdenum disulfide is completely nontoxic. The only effect of massive doses of molybdenum disulfide in acute oral toxicity tests with rabbits was the occurrence of diarrhoea for 24 to 48 hours after dosing. With molybdenum disulfide there was no increase of molybdenum storage in the body. The low toxicity of molybdenum disulfide is due presumably to its chemical inertness and insolubility in body fluids and it has been approved as a lubricant for bakery oven chains by the U.S. Food and Drug Administration. It should, however, be noted that in rats sulfide enhances the toxicity of molybdenum so it cannot be assumed that soluble or more reactive molybdenum-sulfur compounds will be nontoxic.
Acute Toxicities of Molybdenum Compounds towards Animals
|
LD50/mg/l (mg/kg) |
||||
|
Compound |
Animal |
oral |
Intra-peritoneal |
Ref. |
|
MoO3 c |
guinea pig |
LD75 400 |
|
[1,2] |
|
|
rat |
LD50190 |
|
[1,2] |
|
MoO3 (pure) |
rat |
LD50 273 |
|
[3] |
|
|
|
LD50 296-352 |
|
[4] |
|
MoO3 (technical) |
rat |
LD50 666 |
|
[5] |
|
Ammonium molybdate d |
guinea pig |
LD 2200 |
LD100 800 |
[1,2] |
|
|
rat |
|
MLD 203 |
[1,2] |
|
|
rabbit |
LD 1870 |
|
[1,2] |
|
|
cat |
LD1600-3200 |
|
[1,2] |
|
Sodium molybdate |
rat |
MLD 290 |
|
[1,2] |
|
|
|
LD 671 |
|
|
|
|
|
LD50 503 |
|
|
|
|
dog |
|
LD 3200 |
|
|
|
cat |
|
LD1600-3200 |
|
|
|
|
|
LD50 344 |
[6] |
|
Molybdate aq solution e |
chicken |
|
LD100 517+/-83 |
[7] |
|
|
dog |
|
LD1001372+/-441 |
|
|
|
pigeon |
|
LD100 607+/-119 |
|
|
|
rat |
|
LD100 413+/-106 |
|
|
Mo(VI) |
rat |
|
MLD 223 |
[8] |
|
Mo(V) + glucose |
rat |
|
MLD 132 |
[8] |
|
Mo(V ) + ascorbic acid |
rat |
|
MLD 1999 |
[8] |
|
MoS2 |
rat |
|
LD50 > 15 000 |
[9] |
Notes and references
a The definition of toxicity is according to the U.S. Federal Hazardous Substances Labelling Act. The toxicity of the molybdenum compounds listed as toxic is "slight" (e.g., compare sodium arsenate, MLD10 for the rat by intraperitoneal injections). Abbreviations: LD, lethal dose for one animal; LDn, dose killing n% of a group of test animals; MLD, minimum lethal dose, i.e., the smallest of a number of doses which killed one or a group of test animals, all in mg/kg body weight.
b In tests of toxicity by skin absorption, skin irritation, and eye irritation (Test carried out for Climax Molybdenum Co. by Scientific Associates and New Drug Institute) the compounds listed were nontoxic except that ammonium and calcium molybdates were slight eye irritants.
c Some reports of high toxicity of MoO3 are based on the results of long term feeding studies wrongly presented as acute single dose studies
(e.g. LD50 125 mg/kg from L. Fairhall, R. Dunn, N. Sharpless, E. Pritchard, The toxicity of molybdenum, US Public Health Bulletin 293, 1945) (G.G. van Riper and J.C. Gilliland , ULLMANN’S ENCYCLOPEDIA OF INDUSTRIAL CHEMISTRY, 1990, A16, Ch. 12 )
d The description "ammonium molybdate" includes the compounds (NH4)2MoO4, (NH4)2Mo2O7 and (NH4)6Mo7O24.4H2O. There is unlikely to be any difference in the behaviour of the various molybdates.
e After a 60 min intravenous infusion.
[1] Saunders, W. B., Handbook of Toxicology, 1956, London.
[2] Fairhall, L. T., Dunn, R. C., Sharpless, N. E. and E. A. Pritchard, The Toxicity of Molybdenum, U.S. Public Health Service, Public Health Bulletin, 1945, 293
[3] Acute oral LD50 assay in rats FDRL-ID:81-0393 for AMAX Inc. Aug. 1981
[4] Food and Drug Research Laboratories Inc. Acute oral LD50 assay in rats for molybdenum trioxide pure grade, 1981, Waverly New York.
[5] Acute oral LD50 assay in rats FDRL-ID:81-0394 for AMAX Inc. Aug. 1981
[6] Irving Sax, N., Dangerous Properties of Industrial Materials, 1984, 6th Ed. Van Nostrand Reinhold Co. New York, 1953.
[7] Caujolle, F. and Changh, P. H., Agressologie, 1967, 8, 265 (Quoted in Lener, J. and Bibr, B., J. Hygiene, Epidemiology, Microbiology and Immunology, 1984, 28, 405).
[8] Lener, J. and Bibr, B., Proc. Int. Conf.: Heavy Metals in the Environment. Amsterdam 1981, 462. (Quoted in Lener, J. and Bibr, B., J. Hygiene, Epidemiology, Microbiology and Immunology, 1984, 28, 405).
[9] Acute oral LD50 assay in rats of MoS2 FDRL-ID 9589A for AMAX Inc. Nov 29 1987.
Inhalation of dusts of molybdenum trioxide
Inhalation of dusts of molybdenum trioxide (Table below) and the more soluble molybdates produced toxic effects. [Fairhall, 1945] The toxic effect of molybdenum trioxide dust was aggravated by silica [Mogilevskaya, 1961]. Precautions should be taken against the inhalation of dusts of molybdenum trioxide and the more soluble molybdates; maximum permissible concentrations in air recommended by the American Industrial Hygiene Association are 5 mg Mo/m3 (cf. Be, 0.002; V, 0.5; arsine, 0.3) over an eight-hour period. The World Health Organisation recommended in 1969 a "safe concentration zone" of molybdenum as 4-5 mg/m3.
Fairhall, L. T., Dunn, R. C., Sharpless, N. E. and Pritchard, E. A., The Toxicity of Molybdenum, U. S. Public Health Service, Public Health Bulletin, 1945, 293.
Mogilevskaya, O. Ya., Gig. Sanit., 1961, 26, 18.
|
Observable |
Mice, male |
Mice, female |
Rats, male |
Rats, female |
|
Survival |
0 |
0 |
0 |
0 |
|
Mean body weights |
0 |
0 |
0 |
0 |
|
Blood Mo (b) |
+ |
+ |
+ |
+ |
|
Mo toxicity symptoms (c) |
0 |
0 |
0 |
0 |
|
Bone density or curvature |
0 |
0 |
0 |
0 |
|
Nasal and larynx lesions |
+ |
+ |
+ |
+ |
|
Chronic inflammation in lungs |
0 |
0 |
+(d) |
+(d) |
|
Lung carcinoma |
+ |
+ |
0?(e) |
0 (e) |
(a) Groups of 50 male and 50 femaleF344/N rats and B6C3F1 mice were exposed to MoO3 by inhalation at 0, 10, 30, or 100 mg/m3, 6 h/day, 5 days/week, for 2 years. Controls were not exposed. Plus (+) means a positive effect compared with the controls which increases with the level of exposure. Zero (0) means no effect.
(b) Mo concentrations (mg/g): male mice <0.10 (no MoO3) to 0.77 (highest MoO3), female mice 0.04 to 0.52, male rats 0.22 to 6.0, female rats,0.06 to 2.4
(c) e.g. diarrhoea, alopecia, dermatosis, anaemia.
(d) At highest exposures.
(e) For 1/50 animals.
Chan, P.C., Herbert, R.A., Roycroft, J.H., Haseman, J.K., Grumbein, S.L., Miller, R.A., Chou, B.J., Lung tumor induction by inhalation exposure to molybdenum trioxide in rats and mice, Toxicological Sciences, 1998, 45, 58-65.
Molybdenum trioxide inhalation studies in male rats
The following is a detailed summary of a recent study by K. Ozaki et al.
Correlations between non-neoplastic chronic pulmonary lesions and adrenal pheochromocytoma in 9 recent NTP, 2 year particulate inhalation studies in male F344 rats have been investigated. The re-evaluation of other lesions revealed significant associations of pheochromocytoma only with the severity of inflammation and fibrosis. The particulates investigated were all metal compounds and included molybdenum trioxide.
Pheochromocytomas are benign or malignant tumours which give a yellow-brown colour when stained with chromates. These tumours arise as a result of the increased production of catecholamines, such as dopamine, epinephrine and norepinephrine (adrenaline and noradrenaline) in the adrenal medulla in response to a stress which can be an environmental insult. (Catecholamines are synthesised in chromaffin cells.)
Generally exogenous agents that induce adrenal medullary neoplasia do not cause DNA damage so a carcinogenic response is due to an indirect mechanism.
Mammalian tissues are primarily aerobic and hence dependent upon a continuous supply of oxygen. Inadequate O2 delivery results in hypoxemia. Reduction in arterial O2 tension leads to the release of dopamine and other catecholamines. Activity of tyrosine hydroxlyase, the rate limiting step in the biosynthesis of catecholamines is enhanced in the carotid body and the adrenal gland during hypoxemia.
The hypothesis is that the area of lung tissue damaged by the inhalation of certain particulates is correlated positively with the degree of hypoxemia which leads to the pathological increase in tyrosine hydroxylase activity and the production of catecholamines.
The results of the studies relating to MoO3 are given in the following Table.
Results from the re-evaluation of 9 inhalation studies of the particulate compound MoO3 as reported by NTP.
|
Dose |
Control 0 mg m-3 |
Low 10 mg m-3 |
Mid 30 mg m-3 |
High 100 mg m-3 |
|
Lung |
|
|
|
|
|
Proteinosis |
0/50 |
0/50 |
0/50 |
0/50 |
|
Fibrosis, interstitium |
5/50 2.0 |
4/50 1.0 |
7/50 1.0 |
45/50 1.8 |
|
Inflammation, chronic active |
10/50 1.8 |
7/50 1.6 |
37/50 1.2 |
48/50 2.1 |
|
Alveolar epithelium hyperplasia |
12/50 1.8 |
14/50 1.6 |
16/50 1.2 |
7/50 1.3 |
|
Metaplasia, squamous epithelium |
2/50 1.0 |
0/50 |
2/50 1.0 |
27/50 1.1 |
|
Histiocytosis Increase in cells associated with inflammation |
11/50 1.9 |
13/50 1.3 |
35/50 1.3 |
46/50 1.7 |
|
Alveolar/bronchial adenoma |
0/50 |
0/50 |
0/50 |
3/50 |
|
Alveolar/bronchial carcinoma |
0/50 |
1/50 |
1/50 |
1/50 |
|
Adrenal Medulla |
|
|
|
|
|
Pheochromocytoma Benign + malignant |
15/50 |
13/50 |
18/50 |
18/50 |
|
Hyperplasia |
32/50 2.1 |
27/50 2.1 |
28/50 2.1 |
29/50 2.5 |
Second number in each cell indicate the mean grade of severity
0 no involvement
1 min. up to 5 small lesions 10% of area
2 mild 10 - 25 % of area
3 moderate 26 - 50% of area
4 marked 51 - 75% of area
5 severe > 75% of area.
Terms used in the Table:
Proteinosis: Aggregates of homogeneous to granular material which stains with eosin within alveolar lumina.
Fibrosis: Dense fibrous tissue - thickening and scaring of connective tissue. This is considered secondary to inflammation.
Hyperplasia: Enlargement of an organ or tissue arising from the increased production of cells. In the case of the adrenal medulla in this study this is related to the increase in the production of catecholamines.
Metaplasia: Abnormal change in tissue.
Histiocytosis: Accumulation of alveolar macrophages with foamy cytoplasm and occasional multinucleated giant cells but few neutrophils. (Macrophages and neutrophils are associated with inflammation).
Adenoma: A gland-like benign tumour.
Carcinoma: A cancer.
Evaluation
General: In the controls inflammation with a smaller contribution from fibrosis was associated significantly (p<0.01) with the occurrence of pheochromocytomas.
None of the other non-neoplastic lung lesions were significantly correlated with the incidence of adrenal pheochromocytomas.
Molybdenum trioxide showed no dose related increase in pheochromocytoma incidence but the correlation between the incidence of pheochromocytoma and the severities of fibrosis and inflammation was highly significant (p < 0.01) and the strongest correlation was with inflammation.
Molybdenum trioxide showed one of the strongest correlations with inflammation of most test compounds. However, it was not understood why the increase in the incidence of pheochromocytomas did not follow the treatment-related increase in the severity of inflammation and fibrosis.
Pheochromocytomas can also be related to aging or in response to a wide variety of xenobiotic agents BUT these lesions are rare in humans and other animal species. They occur more frequently in male than female rats.
Ozaki, K., Haseman, J. K., Hailey, J. R., Maronpot, R. R., and Nyska, A., Association of adrenal pheochromocytoma and lung pathology in inhalation studies with particulate compounds in the male F344 rat - The national toxicology program experience, Toxicologic Pathology, 2002, 30, 263-270.
International Molybdenum Association toxicity testing programme
|
Substance |
LD50 or LC50/ mg/l |
||
|
|
Acute orala |
Acute inhalationb |
Acute dermalc |
|
|
LD50 rats |
LC50 rats |
LD50 rats |
|
Molybdenum trioxide (pure) |
3260 |
> 5.84 |
> 2000 |
|
Molybdenum trioxide (tech) |
> 5000 |
> 3.93 |
> 2000 |
|
Ammonium dimolybdate |
3883 |
> 2.08 |
> 2000 |
|
Sodium molybdate |
4233 |
> 1.93 |
> 2000 |
|
Molybdenum disulfide |
>2000 |
> 2.82 |
> 2000 |
|
Risk phrase required if:d |
<2000 |
< 5 |
< 2000 |
Notes
a Acute oral is representative of relative toxicity by ingestion. Various doses were administered to rats (10/dose) by infusion into the stomach. Animals were observed for 14 days. For pure molybdenum trioxide there was a statistically significant difference between the oral LD50 in male and female rats: (male, 2689; female, 3830 mg/kg). The value given above is an average and is likely a low estimate.
b Acute inhalation is representative of relative toxicity by inhalation. Dust administered to rats (10) for 4 hours. Animals observed for 14 days.
c Acute dermal is representative of relative toxicity due to skin absorption. Various concentrations adminstered topically to rats (10). Animals observed for 14 days.
Skin irritation: Material applied to rabbit (6) skin for 4 hours. Animals observed for erythema and oedema daily for 4 days.
Eye irritation: Material applied to rabbit (6) eyes (100 mg). Animals observed for 7 days.
Skin sensitization: Guinea pigs exposed to material intradermally and topically twice (induction and challenge).
d All acute oral and dermal results were well above the level that requires a harmful classification and precautionary labelling. In the case of inhalation, in some cases it was not possible to generate a dust cloud of 5 mg/l. However, even at the highest concentrations generated there were no animal deaths and there is no basis to assume that labelling of these materials is indicated.
Toxicity studies on MoS2
Acute inhalation study in rats
The inhalation hazard associated with acute exposure to MoS2 is low.
The LC50 (4 hour) of MoS2 is > 2.82 mg/l in air.
Labelling of MoS2 with the risk phrase R20 Harmful by inhalation is not indicated.
MoS2 was administered as a particulate aerosol at a concentration of 2.82 mg/l of air for 4 h. The rats were observed for 14 d post exposure.
There were no deaths. No clinical signs and no changes of bodyweight compared with controls. Food and water consumption was similar to that of controls.
The ratio lung/body weight was similar to the ratio found for controls.
A grey appearance of the lungs was noted for all rats post mortem.
Acute oral toxicity to the rat
The acute lethal oral dose to rats of molybdenum disulphide was demonstrated to be greater than 2000 mg/kg bodyweight.
Molybdenum disulphide will not require labelling with the risk phrase R22, "Harmful if swallowed", in accordance with Commission Directive 93/2 I/EEC.
A group of ten fasted rats (five males and five females) received a single oral gavage dose of MoS2 formulated in 1% w/v aqueous methylcellulose and administered at a dose level of 2000 mg/kg bodyweight.
There were no deaths. Clinical signs of reaction to treatment in the main study, comprised piloerection, hunched posture and ungroomed appearance observed in all rats. There were no other clinical signs and recovery was complete in all instances by Day 4.
All rats were considered to have achieved satisfactory bodyweight gains throughout the study.
All animals were killed and examined macroscopically on Day 15, the end of the observation period. This examination revealed no abnormalities.
Eye irritation to rabbits
Molybdenum disulfide is not irritating to the eyes.
100 mg of MoS2 was instilled into the eyes of three rabbits. The animals were observed for three days. The MoS2 caused very slight conjunctaval irritation.
Acute dermal toxicity to the rat
Molybdenum disulfide will not require labelling with the risk phrase R21 (EU Commission Directive 93/21/EEC: ‘Harmful in contact with skin.’
The acute lethal dermal dose to rats of MoS2 > 2000 mg/kg bodyweight.
Ten rats received a topical application of MoS2 in 1% w/v aqueous methylcelulose, 2000mg/kg bodyweight.
There was no systemic response to MoS2 .
Four rats showed some dermal irritation which had disappeared 4 d after exposue was stopped.
Skin sensitisation in the guinea-pig
Molybdenum disulphide did not produce evidence of skin sensitisation (delayed contact hypersensitivity) in any of the ten test animals.
Molybdenum disulphide does not require labelling with the risk phrase R43 "May cause sensitisation by skin contact in accordance with Commission Directive 93/21/EEC.
The following dose levels were selected:
Intradermal injection:
10% w/v in Alembicol D
Topical application:
70% w/v in Alembicol D
Challenge application:
70 and 35% w1/v in Alembicol D
Ten test and five control guinea-pigs were used in this study.
Skin irritation to the rabbit
No dermal reactions were observed following a single, semi-occlusive application of molybdenurn disulphide to intact rabbit skin for four hours.
Molybdenum disulphide will not require labelling with the risk phrase R38 ‘Irritating to skin', in accordance with Commission Directive 93/21 /EEC.
Three rabbits were each administered a single dermal dose of 0.5 g of MoS2 and observed for four days.
Huntingdon Life Sciences Ltd Research Laboratory March 1998
Molybdenum metal and metal powder
As with other fine powders inhalation of quantities of molybdenum dust can be dangerous. Safety precautions have been described [Lamprey and Ripley, 1962]. Molybdenum metal as such and in alloys is not toxic and has been incorporated in stainless steels used in bone and joint surgery where resistance to corrosion by body fluids is required [Bechtol et al., 1959]. Molybdenum alloyed with cobalt and chromium has been used for some 40 years for surgical implants, dental prostheses etc. As with the stainless steel, molybdenum confers corrosion resistance.
Lamprey H. and Ripley, R. L., J. of the Electrochemical Soc., 1962, 109, 713.
Bechtol, C. O., Ferguson, B. and Laing, P. G., Metals and Engineering in Bone and Joint Surgery, The Williams and Wilkins Co., Baltimore, 1959.
Workers handling metals in welding and steelmaking are expected to have higher levels of trace metals. Interpretation of levels requires some knowledge of the toxicokinetics of a metal and the preferred medium for analysis for each: serum, whole blood or urine (preferably a 24-hour collection). Trends are often more informative than concentrations at one time. Molybdenum and vanadium are often found to be elevated among workers exposed to metals who show no evidence of clinical illness. The Mo level in the general population not occupationally exposed to Mo (the whole blood Mo reference range) is 5 - 50 nmol/l as used by the Trace Element and Environmental Toxicology Laboratory at the University of Alberta Hospitals. Mo is described as having 'very low toxicity' [Guidotti et al., 1997.]
Guidotti, T.L., Audette, R.J., Martin, C.J., Interpretation of the trace metal analysis profile for patients occupationally exposed to metals, Occupational Medicine-Oxford, 1997, 47 , 497-503.
Molybdenum carbide and silicide
Aqueous suspensions of MoC and MoSi2 administered intraperitoneally to mice in doses of 3000 mg/kg did not cause death [Chem. Abs., 1969]. Intratracheal administration of suspensions of these compounds to rats in doses of 50 mg/animal had pathological effects derived from the fibrogenic nature of the compounds. Maximum permissible concentrations in air are recommended as 6 mg Mo/m3
Chem. Abs., 1969, 71, 68977v.
Brakhnova, I. T. and Samsonov, G. V., Gig. Sanit., 1970, 35, 42.
Molybdenum pentachloride
Molybdenum pentachloride has a marked irritant effect on the tissues of rats [Spiridonova and Surorov, 1967]. The toxicity is due to hydrochloric acid produced during hydrolysis of the compound and not to molybdenum. Molybdenum pentachloride is a hazardous chemical and, if proper precautions are not taken, its industrial use involves danger of acute intoxication. There were no health problems in the production of MoCl5 at the former Climax Langeloth refinery and the Ann Arbor Laboratory.
Spiridonova, V. S. and Suvorov, S. V., Gig. Sanit., 1967, 32, 79.
Molybdenum pentachloride should be considered as a non-immunotoxic and a weak, nonspecific contact irritant. Immunotoxicity was studied in sheep by a 14 day subchronic exposure to MoCl5 at 1- 100 ppm in food. Contact hypersensitivity was determined by topical ear exposure to MoCl5 [Abdouh et al., 1995].
Abdouh, M., Krzystyniak, K., Flipo, D., Therien, H.M., Fournier, M., Cytometric Profile Of Molybdenum-Induced Contact Sensitization Versus A Strong Allergen Reaction To Oxazolone In Murine Auricular Lymph-Node (Aln) Test, International Journal Of Immunopharmacology, 1995, 17, 545-554.
Molybdenum hexacarbonyl and organomolybdenum compounds
Molybdenum hexacarbonyl is a solid which may be handled in the laboratory without special precautions. It is less toxic than the more volatile iron and nickel carbonyls. However, little is known about the toxic effects of molybdenum hexacarbonyl and organomolybdenum compounds [Vignoli and Defretin, 1963] and it is wise to assume that they are likely to be more toxic than MoO3 and molybdates and they should be handled in such a way that there is no danger of absorption through the skin or inhalation of their dusts and vapours.
Vignoli, L. and Defretin, J. P., Biologie medicale, 1963, 52, 319.
Volatile Mo(CO)6 and W(CO)6 are present in landfill gas from three different municipal waste deposits in concentrations of about 0.2-0.3 microg of Mo/m3 and 0.005-0.01 microg of W/m3. The chemical reactions which give rise to these carbonyls under landfill site conditions are not known. Because volatile metal carbonyls are toxic, questions about the occupational health of workers on landfills needs to be addressed [Feldmann and Cullen, 1997].
Feldmann, J., Cullen, W.R..,Occurrence of volatile transition metal compounds in landfill gas: Synthesis of molybdenum and Tungsten carbonyls in the environment, Environmental Science & Technology, 1997, 31, 2125-2129.
Comparative effects of molybdenum and other elements
In comparative toxicity studies with rats and mice sodium molybdate (LD50 1.45 m mol/kg body weight) was less toxic than sodium tungstate, sodium chromate and sodium vanadate [Pham Huu Chanh, 1965]. The irritant effect of sodium molybdate on skin, mucous membranes, and eyes was much smaller than that of sodium dichromate (an extreme irritant) [Climax Molybdenum Test].
Pham-Huu-Chanh, Arch. Intern. Pharmacodyn., 1965, 154, 243.
The ecotoxicological effects expressed as effect on respiratory rate and chlorophyll a content of the freshwater, alga Scenedesmus quadricauda and the bioaccumulation of six ions (Cu2+, Cu+, MoO42-, Mn2+, VO43-, Ni2+) and their associations were determined in comparison with a control [Fargasova, 1998]. The ion concentrations were equal to their EC50 concentrations: for Mo, ammonium heptamolybdate at 2.5 mg l-1. The pH’s of the solutions were not reported. Molybdate had no effect on the respiratory rate; the other ions caused the rate to increase. Combination of moybdate with nickel and copper decreased the rate (but not with manganese). Molybdate and the other ions caused the content of chlorophyll a to decrease. Bioaccumulation of molybdate was negligible MoO42- (< 0.2 %). Molybdate greatly decreased the uptake of Mn, Ni and Cu although these ions had no effect on the uptake of Mo.
Fargasova, A, Accumulation and toxic effects of Cu2+, Cu+, MoO42-, Mn2+, VO43-, Ni2+ and their associations: influence on respiratory rate and chlorophyll (a) content of the green alga Scenedesmus quadricauda, Journal Of Trace And Microprobe Techniques, 1998, 16, 481-490.
Pathological Effects Observed in Experimental Animals
Symptoms of acute molybdenum poisoning and pathological (abnormal)changes in body tissue arising from massive doses by oral and intraperitoneal administration of molybdenum trioxide and ammonium molybdate in lethal or near lethal doses are summarised in Table 7.7 [Browning, 1969].
Browning, E.,Toxicity of Industrial Metals, Butterworths, London, 2nd edn., 1969.
|
Substance and concentration |
Effect |
Ref. |
Sodium molybdate/ppm |
||
|
80-140 |
achromotrichia (loss of hair pigment) |
[1] |
|
75 - 300 |
femuro-tibial joint enlargement |
[2] |
|
75- 400 |
Reduced erythrocyte counts and hemoglobin conc. |
[2,3] |
|
400 |
mandibular and maxillary exostoses |
[3,4] |
|
800-1400 |
diarrhoea |
[3] |
|
400 - 1200 |
Feed consumption and body weight gain reduced |
[5] |
|
400 -1200 |
increased liver xanthine oxidase |
[6] |
|
400-1200 |
increased alkaline phosphatase activities |
[4,7] |
|
400 -1200 |
decreased liver sulfide oxidase, decreased phosphatase and decreased cytochrome oxidase activities |
[8] |
|
400- 1200. |
caused fatty degeneration of the liver and kidney |
[4] |
|
4000-5000 |
death |
[5] |
Sodium molybdate 0.1- 0. 4 % in feed (rabbits ) for 5 weeks |
||
|
(weanlings) |
anorexia, weight loss, decreased erythrocyte counts and hemoglobin concentrations, alopecia, dermatosis, death |
|
|
abnormality of the front legs, bending of the humerus |
[9] |
|
|
Ammonium heptamolybdate oral, in water at 80 mg/kg daily for 8 weeks |
mild chronic renal failure |
[10] |
|
Ammonium molybdate 5 mg/kg per day for 4 to 6 months |
increase in spleen weight, reduction in liver weight |
[11, 12, 13] |
|
Ammonium tetrathiomolybdate (6 mg Mo)and 3 mg copper per kg body weight for 2 to 21 days in feed (weanling male rats ) |
changes at long bone growth plates, at muscle insertions, and beneath the periosteum . |
[14] |
|
molybdenum trioxide dust 1 h ( mice) |
mild irritation of mucous membrane |
[15] |
|
2730 mg/ml molybdenum trioxide (total)dust at 4 h/day for 5.5 months.(rabbits) inhalation |
Reductions in serum alkaline and acid phosphatase activities, decreased inorganic phosphorus levels in tibia, and increased ascorbic acid levels in serum and urine |
[11, 12, 13] |
a rats unless otherwise state
[1] Jeter, M. A. and Davis, G. K., J. Nutr., 1954, 54, 215.
[2] Miller, R. F., Price, N. O. and Engel, R. W., J. Nutr., 1956, 60, 539.
[3] Ostrom, C. A., Van Reen, R. and Miller, C. W., J. Dent. Res., 1961,40, 520.
[4] Van Reen, R., J. Nutr., 1959, 68, 243.
[5] Neilands, J. B., Strong, F. m. and Elvehjem, C. A., J. Biol. Chem., 1948, 172, 431.
[6] Luo, X. -M., Wei, H. -J. and Yang, S. P., JNCI, 1983, 71, 75.
[7] Mills, C. F., Monty, K. J., Ichihara, A. and Pearson, P. B., J. Nutr., 1958, 65, 129.
[8] Mills, C. F. and Davis, G.K., in "Trace Elements in Human and Animal Nutrition", Metrz, W., ed., 5th Ed. 1987, 1, 429. Academic Press. Inc., San Diego.
[9] Arrington, L.R. and Davis, G. K., J. Nutr., 1953, 51, 295.
[10] Bompart, G., Pecher, C., Prevot, D. and Girolami, J. -P., Toxicol. Lett., 1990, 52, 293.
[11] Lukashev, A. A. and Shishkova, Tr. Nauch.-Issled. Inst. Kraev. Patol. Alma Ata, 1971, 22, 152.
[12] Lukashev, A. A. and Shishkova, Tr. Nauch.-Issled. Inst. Kraev. Patol. Alma Ata, 1971, 22, 175.
[13] Lukashev, A. A. and Shishkova, Tr. Nauch.-Issled. Inst. Kraev. Patol. Alma Ata, 1971, 22, 191.
[14] Spence, J. A., Shuttle, N. F., Wenham, G., El-Gaim, T. and Bremner, I., J. Comp. Pathol., 1980, 90, 139.
[15] ACGIH: American Conference of Governmental Industrial Hygienists, 1992.
Symptoms of acute molybdenum poisoning
High doses of soluble molybdates caused experimental animals to become listless and to lose their appetites. Their physical condition deteriorated; their hair became harsh and rough and was easily removed; they lost weight. Loss of weight or a decreased rate of weight increase compared with controls is general with animals fed large doses of molybdenum compounds [Johnson et al., 1969]. In high doses molybdenum has a deleterious effect on bones and skin. The breaking strength of femurs, skin, and tail ring was decreased in molybdenum fed rats [Johnson et al., 1969]and rabbits developed a deformity of the forelegs. Bodily functions were impaired leading to diuresis and hypersalivation.
Johnson, R. H., Little, J. W. and Bickley, H. C., J. Dent. Res., 1969, 48, 1290.
Sodium molybdate, 2000 mg/kg in aqueous solution, was given intragastrically to rats. There were no deaths. Mo caused a high urinary excretion of N-acetyl-beta-glucosaminidase, a reduction in serum proteins and an increase in lactate dehydrogenase. There were no histopatholgical changes to organs. Since the LD50 of molybdate is greater than 2000 mg/kg it should be described as 'not toxic' according to Directive 83/467/EC [Rodriguez-Consuegra et al., 1994].
Rodriguez-Consuegra, M.A., Rodriguez-Vicente, M.C., Martinez, M.C., Repetto, M., Acute oral toxicity study of molybdenum in Wistar and Brown Norway rats, Rev. Toxicol.,1994, 11, 122 - 126.
Histopathological changes in acute molybdenum poisoning
The liver and kidneys were most affected. Cells became swollen and fat globules were deposited. The extent of damage increased with increasing exposure to molybdenum compounds [Table 7.7].
|
Substance and concentration |
Effect |
Ref. |
Sodium molybdate/ppm |
||
|
80-140 |
achromotrichia (loss of hair pigment) |
[1] |
|
75 - 300 |
femuro-tibial joint enlargement |
[2] |
|
75- 400 |
Reduced erythrocyte counts and hemoglobin conc. |
[2,3] |
|
400 |
mandibular and maxillary exostoses |
[3,4] |
|
800-1400 |
diarrhoea |
[3] |
|
400 - 1200 |
Feed consumption and body weight gain reduced |
[5] |
|
400 -1200 |
increased liver xanthine oxidase |
[6] |
|
400-1200 |
increased alkaline phosphatase activities |
[4,7] |
|
400 -1200 |
decreased liver sulfide oxidase, decreased phosphatase and decreased cytochrome oxidase activities |
[8] |
|
400- 1200. |
caused fatty degeneration of the liver and kidney |
[4] |
|
4000-5000 |
death |
[5] |
Sodium molybdate 0.1- 0. 4 % in feed (rabbits ) for 5 weeks |
||
|
(weanlings) |
anorexia, weight loss, decreased erythrocyte counts and hemoglobin concentrations, alopecia, dermatosis, death |
|
|
abnormality of the front legs, bending of the humerus |
[9] |
|
|
Ammonium heptamolybdate oral, in water at 80 mg/kg daily for 8 weeks |
mild chronic renal failure |
[10] |
|
Ammonium molybdate 5 mg/kg per day for 4 to 6 months |
increase in spleen weight, reduction in liver weight |
[11, 12, 13] |
|
Ammonium tetrathiomolybdate (6 mg Mo)and 3 mg copper per kg body weight for 2 to 21 days in feed (weanling male rats ) |
changes at long bone growth plates, at muscle insertions, and beneath the periosteum . |
[14] |
|
molybdenum trioxide dust 1 h ( mice) |
mild irritation of mucous membrane |
[15] |
|
2730 mg/ml molybdenum trioxide (total)dust at 4 h/day for 5.5 months.(rabbits) inhalation |
Reductions in serum alkaline and acid phosphatase activities, decreased inorganic phosphorus levels in tibia, and increased ascorbic acid levels in serum and urine |
[11, 12, 13] |
a In lethal or near-lethal dose. Abbreviations: ingest., ingestion in food; inhal., inhalation of dust; i.p., intraperitoneal injection; or., oral administration. See also note d of Table 2.a(i).
[1] Test carried out for Climax Molybdenum Co. by Scientific Associates and New Drug Institute.
[2] Browning, E., Toxicity of Industrial Metals, Butterworths, London, 2nd edn., 1969.
[3] Fairhall, L. T., Dunn, R. C., Sharpless, N. E.and Pritchard, E. A., The toxicity of molybdenum ,US Public Health Service, Public Health Bulletin, 1945, 294.
[4] (a) Underwood, E. J., Trace Elements in Human and Animal Nutrition, Academic Press, London, 2nd Ed., 1962, 100. (b) Kolomiitseva, M. G., Polonskaya, M. N.and Osipov, G. K., Mikroelem. Sel. Khoz. Med., 1968, 4, 183.(c) Schroeder, H. A.,. Balassa, J. J.and Tipton, I. H., J. Chronic Diseases, 1970, 23, 481.
Histopathological Changes in Acute Molybdenum Poisoning in Test Animals a
|
Organ |
Animal |
Changes observed |
|
Adrenals |
guinea pig, rat |
congested and swollen |
|
Gastrointestinal tract |
rat |
stained deep blue |
|
Heart |
guinea pig |
no change |
|
Kidneysb |
guinea pig |
some cells swollen, fat globules deposited |
|
Liverb |
guinea pig |
cells swollen, fat globules deposited |
|
Lungs |
guinea pig |
slight to moderate congestion, cellular exudate |
a MoO3 and ammonium molybdate administered orally, intraperitoneally, and by inhalation.
b Organs most affected.
[1] (a) Underwood, E. J., Trace Elements in Human and Animal Nutrition, 2nd Ed. 1962, 100, Academic Press, London. (b) Kolomiitseva, M. G., Polonskaya, M. N. and Osipov, G. K., Mikroelem. Sel. Khoz. Med., 1968, 4, 183. (c) Schroeder, H. A., Balassa, J. J. and Tipton, I. H., J. Chronic Diseases, 1970, 23, 481.
[2] Test carried out for Climax Molybdenum Co. by Scientific Associates and New Drug Institute.
[3] Browning, E., Toxicity of Industrial Metals, 2nd Ed., 1969, Butterworths, London.
[4] Fairhall, L.T., Dunn, R. C., Sharpless N. E. and Pritchard, E. A., The toxicity of molybdenum, US Public Health Service, Public Health Bulletin, 294, 1945.
IMOA Testing Programme Skin and Eye Irritation a
|
Substance |
Test |
||
|
|
skin irritation b |
eye irritation c |
skin sensitisation d |
|
Molybdenum trioxide (pure) |
none |
mild inflammation |
0% positive |
|
Molybdenum trioxide (tech) |
none |
mild inflammation |
0% positive |
|
Ammonium dimolybdate |
none |
mild inflammation |
20% positive |
|
Sodium molybdate |
none |
mild inflammation |
4% positive |
|
Risk phrases required if: |
significant irritation |
significant inflammation |
>30% |
Notes
a Combination of 4 tests. Results may be affected by pH and/or alkali content of the sodium molybdate.
b Skin irritation: Material applied to skin of rabbits (6) for 4 hours. Animals observed for erythema and oedema daily for 4 days. No irritation was noted in any animals.
c Eye irritation: Material applied to eyes of rabbits (6) (100 mg). Animals observed for 7 days. Only mild transient irritation was observed in test animals.
d Skin sensitization: Guinea pigs exposed to material intradermally and topically twice (induction and challenge). Sodium molybdate with low alkali content gave positive reactions at frequencies of less than 30%. Higher frequencies were obtained in high alkali samples. It is uncertain if these were sensitization or irritation reactions.
Bacteria
|
Substance |
Toxicity/ mg/l |
|
|
|
Acute bacterial growth inhibition |
Acute bacterial respiratory inhibition |
|
|
EC10 b |
3 h EC50 c |
|
Molybdenum trioxide (pure) |
d |
820 |
|
Molybdenum trioxide (tech) |
d |
3000 |
|
Ammonium dimolybdate |
13 |
|
|
Sodium molybdate |
50 |
|
Notes
a There are no EC criteria for bacterial toxicity. It is however factored into the German Water Hazard Classification. Under the German classification scheme, which takes into account fish, mammal and bacterial toxicity, the materials tested would give a maximum Water Hazard Classification of 1(weak hazard for waters).
b The EC10 is the concentration that causes a 10% reduction in turbidity. Test culture incubated with various concentrations of test substance for 18 hours. Turbidity measured by light transmission.
c The EC50 is the concentration that causes a 50% reduction in respiration. Test culture and test substance were left in contact for 30 minutes and three hours. At the end of each time period the dissolved oxygen content of the solution was measured.
d Growth inhibition is determined by the decrease in turbidity of test solution. Therefore, this method cannot be used on insolubles.
Molybdenum toxicity studies with fish
|
Substance |
Toxicity/ mg/l |
||
|
|
acute fish a |
acute daphnids b |
algal growth c |
|
|
96 h LC50 |
48 h EC50 |
72 h IC50 |
|
Molybdenum trioxide (pure) |
130 |
150 |
100 |
|
Molybdenum trioxide (tech)d |
77 |
88 |
100 |
|
Ammonium dimolybdatee |
420 |
140 |
41 |
|
Sodium molybdate |
7600 |
330 |
>100 |
|
Risk phrase required if: |
<100 |
<100 |
< 100 |
Notes
a Acute fish toxicity is representive of relative toxicity to aquatic vertebrates. Trout used because of large data base and sensitivity. Rainbow trout (10/concentration) exposed to various concentrations under semi-static conditions for 96 hours.
b Acute daphnia toxicity is representative of relative toxicity to aquatic invertebrates. Dapnids are ubiquitous thoughout the world in fresh water ponds and lakes, important link in food chain. Daphnids (20/concentation) exposed to various concentrations under static conditions for 48 hours. Daphnids observed for immobilization and Effective Concentration, EC50 calculated.
c Algal growth inhibition is representative of relative toxicity to aquatic plants. Algae are primary producers in the food chain. Inhibition can alter food web and reduce productivity of ecosystems. Stimulation may cause algal blooms, causing anoxic conditions, negative anaesthetic effects, etc. Test cultures of algae were prepared and added to solutions of test material and incubated for 72 hours. Growth was monitored by measuring the absorbance of each culture at 665 nm. The median effective concentration for inhibition of growth (IC50 ) after 72 hours was calculated.
d The aquatic toxicity of technical oxide varied with the level of impurities, particularly copper. High copper content samples gave lower results in the daphnia studies.
e The toxicity of ammonium molybdate to algae is not unexpected considering the the known toxicity of ammonia, which is commonly used as a bactericide and disinfectant.
|
LD50/mg/l |
|||||
|
Compound |
Species |
24h |
48h |
96h |
No effect Level |
|
MoO3 [1] |
bluegill |
87-120 |
87-120 |
87 |
75 |
|
|
rainbow trout |
102 |
65-87 |
65-87 |
65 |
|
Ammonium dimolybdate[2] |
bluegill |
166 |
157 |
157 |
140 |
|
|
rainbow trout |
138 |
135 |
120 |
87 |
|
Sodium molybdate [2] |
bluegill |
> 10,000 |
- |
6,790 |
2,400 |
|
|
rainbow trout |
> 10,000 |
- |
7,340 |
3,200 |
|
|
channel catfish |
> 10,000 |
- |
> 10,000 |
7,500 |
|
|
fathead minnow |
> 10,000 |
- |
7,630 |
5,600 |
|
Sodium molybdate [3] |
shrimp |
3997 |
- |
- |
- |
|
|
minnow |
6590 |
- |
- |
- |
|
|
American oyster (EC50) |
3526 |
- |
- |
- |
[1] Bentley, R. E., Acute Toxicity of Ammonium Molybdate and Molybdic Trioxide to Bluegill (Lepomis macrochirus) and Rainbow Trout (Salmo gairdneri),Bionomics, Wareham, Massachusetts, 1975, January
[2] Bentley, R. E., Acute Toxicity of Sodium Molybdate to Bluegill (Lepomis macrochirus), Rainbow Trout (Salmo gairdneri), Fathead Minnow (Pimephales promeals), Channel Catfish (Ictalurus punctatus), Water Flea (Daphnia magna) and Scud (Gammarus fasciatus),Bionomics, Wareham, Massachusetts, 1973, December.
[3] Knothe, D. W. and van Riper, G. G., Bull. Environ. Contam. and Toxicol., 1988, 40, 785.
Sodium molybdate was found to be significantly less toxic to several varieties of fish than either molybdic oxide or ammonium dimolybdate [ Bentley, 1973; 1975].
Bentley, R. E., Acute Toxicity of Sodium Molybdate to Bluegill (Lepomis macrochirus), Rainbow Trout (Salmo gairdneri), Fathead Minnow (Pimephales promeals), Channel Catfish (Ictalurus punctatus), Water Flea (Daphnia magna) and Scud (Gammarus fasciatus), Bionomics, Wareham, Massachusetts, 1973.
Bentley, R. E., Acute Toxicity of Ammonium Molybdate and Molybdic Trioxide to Bluegill (Lepomis macrochirus) and Rainbow Trout (Salmo gairdneri), Bionomics, Wareham, Massachusetts, 1975.
Toxicity rainbow trout
The purpose of the study was to resolve inconsistencies in reported bioassays of the toxicity of molybdenum (as sodium molybdate in water) to fertilized rainbow trout eggs and alevins (EA) for which a wide toxicity range (LC50 0.73 to >90 mg/L Mo) has been reported. Molybdenum was not acutely toxic to the early life stages of rainbow trout (32 d, maximum molybdenum concentration 400 mg l-1). When early life stages of rainbow trout were exposed to a maximum molybdenum concentration of 1500 mg l-1 for 32 d there was not sufficient mortality for an LC50 to be calculated. The importance of careful control of the water chemistry in the bioassay was emphasized.
Davies, T. D., Pickard, J., and Hall, K. J., Acute molybdenum toxicity to rainbow trout and other fish, Journal of Environmental Engineering and Science, 2005, 4, 481-485.
Aquatic Organisms
The benthic [sediment] organisms Chironomus plumosus larvae and Tubifex tubifex worms may be used as aquatic toxicity indicators of metals which may accumulate in freshwater sediments as a consequence of heavy metal contamination of water. The LC50 values after 96 h are given in the Table. The tests were carried out in boiled tap water (20 C, pH 7 - 8, calcium carbonate hardness 80 mg l-1). Molybdate (supplied as ammonium hepatamolybdate) is the least toxic of the metals on both a mass and molar basis and is non-toxic, its LC50 value being less than concentrations found in the environment.
|
|
C. plumosus |
T. tubifex |
||
|
Compound |
103LC50/mg l-1 |
103LC50/ mol l-1 |
103LC50/mg l-1 |
103LC50/ mol l-1 |
|
V2O5 |
218 |
4.28 |
211 |
4.14 |
|
(NH4)6Mo7O24.4H2O |
455 |
4.74 |
4563 |
47.6 |
|
MnSO4.H2O |
68 |
1.24 |
295 |
5.37 |
|
NiSO4.7H2O |
266 |
4.53 |
537 |
9.15 |
|
CuSO4.5H2O |
0.105 |
0.00165 |
2 |
0.0315 |
|
Cu2Cl2 |
0.927 |
0.0146 |
6 |
0.0945 |
Fargasova, A, Comparative acute toxicity of Cu2+, Cu+, Mn2+, Mo6+, Ni2+ and V5+ to Chironomus plumosus larvae and Tubifex tubifex worms, Biologia, 1998, 53, 315-319.
Mo toxicity towards flannelmouth sucker
Larval flannelmouth sucker (Catostomus latipinnis) were exposed to inorganics which simulated environmental ratios reported for sites along the San Juan River. The toxicity rank order was copper > zinc >vanadium > selenite > selenate > arsenate > uranium > boron > molybdenum.
Hamilton, S.J., Buhl, K.J., Hazard evaluation of inorganics, singly and in mixtures, to flannelmouth sucker Catostomus latipinnis in the San Juan River, New Mexico, Ecotoxicology And Environmental Safety, 1997, 38, 296-308.
Toxicity towards Daphnia
Molybdates are alternatives to toxic chromates in industrial applications, e.g. passivation of zinc coatings in the automobile industry. Molybdates are much less toxic than chromates although both molybdenum and chromium and their compounds are included in th List II of European dangerous substances directive (Council of the European Communities (1976). Directive of 4 May 1976 on Pollution Caused by Certain Dangerous Substances and Discharged into the Aquatic Environment of the Community (76/464/EEC, OJL 129, 18 May). The purpose of the work described in this paper was to compare the aquatic acute and chronic toxicity of Mo and Cr in standard tests with the organism Daphnia magna, and in acetylcholinesterase inhibition.
|
Chemical |
48 h LC50/mg L-1 |
95% confidence limit |
|
Sodium dichromate |
0.29 |
0.269-0.315 |
|
Sodium molybdate |
2848 |
2839-2857 |
|
Chemical |
Total growth |
Reproduction |
Mortality |
||||||
|
|
NOEC |
LOEC |
EC50 |
NOEC |
LOEC |
EC50 |
NOEC |
LOEC |
EC50 |
|
Sodium dichromate |
0.0125 |
0.025 |
0.233 |
0.0125 |
0.025 |
0.047 |
0.075 |
0.01 |
0.524 |
|
Sodium molybdate |
50 |
75 |
204 |
50 |
75 |
102 |
75 |
100 |
255 |
|
Chemical |
NOEC/mg L-1 |
LOEC/mg L-1 |
EC50 /mg L-1 |
|
Sodium dichromate |
0.075 |
0.15 |
0.632 |
|
Sodium molybdate |
750 |
1500 |
26.5 |
a No inhibition in vitro
The study shows that sodium molybdate is much less toxic towards Daphnia magna than is sodium dichromate.
Diamantino, T.C., Guilhermino, L., Almeida, E., and Soares, A. M. V. M., Toxicity of sodium molybdate and sodium dichromate to Daphnia magna Straus evaluated in acute, chronic, and acetylcholinesterase inhibition tests, Ecotoxicology and Environmental Safety, 2000, 45, 253-259.
Effects on the nervous system
Conditioned reflexes of white rats inoculated with industrial dust containing molybdenum in the form of oxides and metal powder were examined [IOG154, 1965]. The strength and activity of fundamental nervous processes were upset and the excitation processes were weakened by molybdenum. The rats inoculated with molybdenum lagged behind the control group in overall development. We have been unable to ascertain the molybdenum concentrations used in this work.
IOG154, Referativnyy Zhurnal-Metallurgiya, 1965, 10, 1OG154.
Reproductive and developmental toxicity
Sodium molybdate added to the feed of rats from the time of weaning (80 or 140 ppm during 8 weeks) resulted in fewer litters and impaired growth of pups [Jeter and Davis,1954]. The effect of Dietary molybdenum had effects upon the hemoglobin, growth, reproduction and lactation of rats [Jeter and Davis, 1954; Schroeder and Mitchener, 1971]. Sodium molybdate did not induce embryonic toxicity when injected into the yolk sacs of 4- and 8-day-old chick embryos [Ridgway and Karnofsky, 1952]. Radioactive 99Mo administered orally to pregnant sows was not present in the fetus. However, demyelination of the cerebral nervous system was observed in the newborn lambs from pregnant ewes were fed a diet high in molybdate [Mills and Fell, 1960].
Jeter, M. A. and Davis, G. K., J. Nutr., 1954, 54, 215.
Schroeder, H. A., Mitchener, M. and Nason, A. P., J. Nutr., 1971, 101, 247.
Schroeder, H. A. and Mitchener, M., Arch. Environ. Health, 1971, 23, 102.
Ridgway, L. P. and Karnofsky, D. A., Ann. N.Y. Acad. Sci., 1952, 55, 203.
Mills, C. F. and Fell, B. F., Nature, 1960, 185, 20.
The effect of molybdenum on estrous activity and reproductive hormones: LH, FSH and estradiol in Wistar weanling female rats whose diet was supplemented, inter alia, with 500 ppm Na2MoO4. High dietary Mo prolonged the length of the estrous cycle and altered the cytological characteristics of the different phases of the cycle. Peak values of FSH were significantly lower in molybdenotic animals and Serum E(2) was lower [Igarza et al.,1996].
Igarza, L., Agostini, M., Becuvillalobos, D., Auza, N., Effects Of Molybdenosis On Luteinizing-Hormone, Follicle-Stimulating And Estradiol Hormones In Rats, Archivos De Medicina Veterinaria , 1996, 28, 101-106.
Molybdenum and cancer
Molybdenum trioxide has been reported to be weakly carcinogenic in mice in a short-term (30 week) lung adenoma assay at high doses (4 750 mg/kg total) but not at lower doses [Stoner et al., 1976]. The reported carcinogenicity of molybdenum orange pigment (a mixture of lead chromate and lead molybdate) injected subcutaneously injection to rats is likely due to the lead and chromium rather than the molybdenum since lead chromate is a carcinogen [Maltoni (a), 1976; Maltoni (b), 1976].
Stoner, G. D., Shimkin, M. B., Troxell, M. C., Thompson, T. L. and Terry, L. S., Cancer Res., 1976, 36, 1744.
Maltoni, C., Ann. N.Y. Acad. Sci., 1976, 271, 431.
Maltoni, C., Ann. N.Y. Acad. Sci., 1976, 271, 444.
In the rat azoxymethane induced aberrant crypt foci have been suggested to be biological precursors to colon cancers. The effects of 41 potential chemopreventive agents in the F344 rat using the inhibition of carcinogen-induced aberrant crypt foci in the colon as the measure of efficacy were assessed [Wargovich et al., 1996]. Aberrant crypt foci were induced by the carcinogen azoxymethane. Twenty-three agents did not inhibit aberrant crypt foci; among these were several agents, including sodium molybdate, that promoted the development of aberrant crypt foci at one or both doses tested. The average yield of aberrant crypts for the azoxymethane-only group was 88 8 aberrant crypt foci/colon. When the diet included sodium molybdate (0.05 g/kg diet) the yield of aberrant crypts was 103 8 significantly greater than control group.
Wargovich, M.J., Chen, C.D., Jimenez, A., Steele, V.E., Velasco, M., Stephens, L.C., Price, R., Gray, K., Kelloff, G.J., Aberrant Crypts As A Biomarker For Colon-Cancer - Evaluation Of Potential Chemopreventive Agents In The Rat, Cancer Epidemiology Biomarkers & Prevention, 1996, 5, 355-360.
The potential toxicities of organic and some inorganic compounds have been predicted by a computer program which correlates toxicity with molecular properties [Lewis et al.,1996]. The program is called COMPACT (Computer Optimised Molecular Parametric Analysis for Chemical Toxicity: CYP1A and CYP2E1). Evaluations were also made by Hazard expert, and for metal ion redox potentials; and these, together with COMPACT, were compared with results from the Ames test for mutagenicity in Salmonella, the micronucleus test and 90-day subchronic rodent pathology. According to the abstract, molybdenum trioxide is a metal compound with a redox potential of the metal/metal ion indicative of possible carcinogenicity and the prediction for carcinogenicity was positive for molybdenum trioxide. However, it is clear from the body of the paper that this statement is most misleading. The programs gave no prediction for molybdenum trioxide. The reference to the redox potential is to the Mo(III)/Mo(IV) couple allegedly 0.32 V oxidising and so having carcinogenic potential. This potential is hardly relevant since MoO3 is Mo(VI) and the relevant potential is Mo(VI)/Mo(V), 0.4 V.
Lewis, D.F.V., Ioannides, C., Parke, D.V., Compact And Molecular-Structure In Toxicity Assessment - A Prospective Evaluation Of 30 Chemicals Currently Being Tested For Rodent Carcinogenicity, Environmental Health Perspectives, 1996, 104, 1011-1016.
Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, vanadium pentoxide, and nickel sulfate heptahydrate were tested in the Syrian hamster embryo (SHE) assay in order to increase the SHE assay database for heavy metals [Kerckaert et al., 1996]. All five compounds produced significant morphological transformation {MT) at one or more doses in a dose-responsive manner. Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, and nickel (II) sulfate heptahydrate were all positive with a 24-h exposure, suggesting direct DNA perturbation. Vanadium pentoxide was negative with a 24-h exposure, but positive with a 7-day exposure. This pattern of response (24-h SHE negative/7-day SHE positive) has been seen with other chemicals which have tumour promotion-like characteristics. MoO3 in a 24 h exposure to SHE cells with culture medium as the solvent gave a significant increase in SHE cell MT in four doses =/> 75 microg/ml and 67% cytotoxicity at the top dose of 200 microg/ml. The Mo value compares with Ni 5 microg/ml and Co 1 microg/l.
Kerckaert, G.A., Leboeuf, R.A., Isfort, R.J., Use Of The Syrian-Hamster Embryo Cell-Transformation Assay For Determining The Carcinogenic Potential Of Heavy-Metal Compounds, Fundamental And Applied Toxicology, 1996, 34, 67-72.
Chronic exposure of animals to molybdenum oxide fumes (53 mg/m3 for 1 h daily) produced pulmonary irritation and fatty changes in the liver and the kidney, but no deaths occurred [Smyth, 1956.]
Smyth, H.E., Hygienic standard for daily inhalation. Ind Hyg Q, 1956,17,129-185.
The results of a study of the respiratory effects of inhalation of air-borne MoO3 dust during two years are summarised in Table 7.2 [Chan et al., 1998]. Although the blood concentration of Mo increased as a consequence of the Mo exposure toxic symptoms were not observed. Prolonged inhalation of MoO3 dusts was harmful to the respiratory system of the mice and rats. The effect of MoO3 is similar to that of talc, nickel oxide and nickel subsulfide and irritants generally in inhalation studies. There is, however, a species dependence and some of the effects are marginal. Whether inhalation of MoO3 induces carcinomas is of particular interest. The number of animals experiencing adenoma or carcinoma at the highest MoO3 exposures were: male mice 9/50 and 10/50, female mice 9/49 and 6/49; male rats 3/50 and 1/50, female rats 2/50 and 0/50. The exposure (100 mg m-3) is ten times the US workplace threshold limit value. The authors comment that MoO3 is not mutagenic.
Chan, P.C., Herbert, R.A., Roycroft, J.H., Haseman, J.K., Grumbein, S.L.,Miller, R.A., Chou, B.J., Lung tumor induction by inhalation exposure to molybdenum trioxide in rats and mice, Toxicological Sciences, 1998, 45, 58-65.
Anti-cancer properties of molybdenum
Sodium molybdate administered in drinking water has a protective action against the induction of cancer in rats by organic N-nitroso compounds [Luo , X.-M.et al.,1983]. Inhibitory effects of molybdenum on oesophageal and forestomach carcinogenesis in rats have been reported [Komada, H. et al., 1990] and the effect of dietary molybdenum on oesophageal carcinogenesis in rats induced by N-methyl-N-benzylnitrosamine [Wei, H.-J et al., 1985]. Effects of molybdenum and tungsten on mammary carcinogenesis are found in SD rats.[ Seaborn and Yang, 1993]. Molybdenum supplementation affects N-nitroso- N-methylurea-induced mammary carcinogenesis and molybdenum excretion in rats [Kopf-Meyer, 1979].
Luo, X. M., Wei, H. J. and Yang, S. P., J.Nat.Cancer Inst.,1983, 71, 75.
Komada, H., Nakagawa, M., Yamamura, M., Hioki, K. and Yamamoto, Cancer Res., 1990, 50, 2418.
Wei, H. J., Luo, X. M. and Yang, S. P., J.Nat.Cancer Inst., 1985, 74, 469.
Seaborn, C. D. and Yang, S. P., Biol. Trace Elem. Res., 1993, 39, 245.
Kopf-Meyer, P., Naturforsch., 1979, 34, 1174.
Molybdenum dichloride has anti-tumour agent properties [Koizumi et al., 1995]. Suppressive effects of molybdenum on hepatotoxicity of N-nitrosodiethylamine in rats have been reported.
Koizumi, T., Tajima, K., Emi, N., Hara, A., Suzuki, K.T., Suppressive Effect Of Molybdenum On Hepatotoxicity Of N-Nitrosodimethylamine In Rats, Biological & Pharmaceutical Bulletin, 1995, 18, 460-462.
The beneficial effect of the molybdenum is due to the denitrosation of the nitroso compound. Molybdenum is also a biological antagonist of cancer-producing copper [Nederbragt, 1982].
Nederbragt, H., Br. J. Nutr., 1982, 48, 353.
Molybdenum prevents the carcinogenesis of N-nitroso compounds [Koizumi et al., 1995]. Male Wistar rats weighing 170-190 g were pretreated with sodium molybdate, Na2MoO4 (1.24 mmol/kg body weight, i.p., once a day) for 3 d and on day 4, they were exposed to N-nitrosodimethylamine (50 mg/kg body weight, once, i.p.). Na2MoO4-pretreatment prevented both nitrosodimethylamine-induced DNA damage and disruption of the metabolism of K and Ca but rather enhanced lipid peroxidation.Mo prevented N nitrosodimethylamine-induced DNA damage by preventing disruption of intracellular Ca metabolism while stimulating the metabolism of the nitroso compound via a nontoxic pathway.
Koizumi, T., Tajima, K., Emi, N., Hara, A. and Suzuki, K.T., Biol. Pharm. Bull., 1995, 18, 460.
Genetic Toxicity
Molybdenum trioxide was not mutagenic in tests with Bacillus subtillis , [Kada et al., 1980], Salmonella typhimurium, [Zeiger et al., 1992; Milvy and Kay, 1978], and Escherichia coli , [Venitt and Levy, 1974].
Kada, T., Hirano, K. and Shirasu, Y., in : Chemical Mutagens: Principles and Methods for their Detection.
Zeiger, E., Anderson, B., Haworth, S., Lawlor, T. and Mortelmans, K., Environ. Mol. Mutagen, 1992, 19 (Suppl. 21), 2.
Milvy, P. and Kay, K., J. Tox. Environ. Health, 1978, 4, 31.
Venitt, S. and Levy, L.S., Nature,1974, 250, 493.
Increased frequencies of chromosomal aberrations were reported in peripheral blood lymphocytes of experimental animals and workers exposed to molybdenum, molybdenite, and molybdenum trioxide [Babaian et al., 1980].
Babaian, E.A., Bagramian, S.B., and Pogosian, A.S., Gig. Tr. Prof. Zabol., 1980, 9, 33.
Cytotoxicity of molybdenum trioxide nanoparticles
There is a lack of information about the impact of nanomaterials on human health and the environment. The purpose of the study was to assess a mouse spermatogonial stem cell line (C18—4from type A spermatogonia isolated from 6-day-old mouse testes) as a model to assess nanotoxicity in the male germline in vitro. The effects of different types of nanoparticles on these cells were evaluated. MoO3 nanoparticles (30 microm) were made in a pulsed plasma reactor which forms the particles in a gas-phase process. There was a concentration-dependent toxicity for all types of particle (MoO3 , CdO, Ag, Al) tested, whereas the corresponding soluble salts had no significant effect. Molybdenum trioxide MoO3 nanoparticles were the least toxic. This cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro. With respect to their mitochondrial function MoO3 nanoparticles had a toxic effect of cellulsar metabolic activity at concentrations of 50 microg/l and above: EC50 90 microg/l. By contrast sodium molybdate in aqueous solution at the same concentrations was hardly toxic (EC50 322 microg/ml). In the LDH leakage test sodium molybdate did not affect the integrity of the plasma membrane whereas a significant increase of LDH leakage was observed with molybdenum nanoparticles: EC50 5 microg/l.
Braydich-Stolle, L., Hussain, S., Schlager, J. J., and Hofmann, M. C., In vitro cytotoxicity of nanoparticles in mammalian germline stem cells, Toxicological Sciences, 2005, 88, 412-419.
The toxicity of (inter alia) MoO3 nanoparticles (30 and 150 nm) was investigated in an in vitro model derived from rat liver cells BRL 3A. The interest was the cellular response to nanosized particle exposure. For toxicity evaluations cellular morphology, mitochondrial function (MTTassay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH) levels, reactive oxygen species (ROS),and mitochondrial membrane potential (MMP) were assessed under control and exposed conditions (24 h exposure) and at MoO3 concentrations from 0 to 250 ug/l. For MoO3 exposure at concentrations up to 100 microg/l the results of the LDH leakage and MTT assays showed no cytotoxicity but showed a significant effect at 250 microg/l.. The results were summarised as EC50 values (i.e. the concentration of nanoparticles that increased LDH leakage to 50% or decreased MTT reduction by 50%: MTT: 172 ± 25 (30 nm),175 ± 26 (150 nm); LDH: 210 ± 30 (30 nm)and 250 ± 17 (150 nm). MoO3 was less toxic than Ag and CdO but more so than, Fe3O4, Al, MnO2 and W particles.
Hussain, S.M., Hess, K. L., Gearhart, J. M., Geiss, K. T., and Schlager, J. J., In vitro toxicity of nanoparticles in BRL 3A rat liver cells, Toxicology in Vitro, 2005, 19, 975-983.
Mutagenicity
The mutagenic effect of an industrial enterprise (tungsten and molybdenum factory) was studied in three stages. At the first stage, the putative impact of the industrial sewage of the factory was studied using three plant test systems: Crepis capillaris L., Tradescantia sp. clone 02, and Glycine max (L.) Merill. It was found that the sewage increased the mutation level by a factor of 11-45. At the second stage, the rate of mutation was studied in the native vegetation growing on solid waste piles of the enterprise. It exceeded the corresponding index of uncontaminated areas by a factor of 2.0-4.5. At the third stage, the rates of children with birth defects and miscarriages were studied in the vicinity of the enterprise. The rate of miscarriages proved to be higher than the value averaged over the autonomous republic by a factor of 2.4. No change in the rate of birth defects was detected
Reutova, N.V., Vorobyeva, T. I., and Reutova, T. V., Some approaches to evaluation of the mutagenic effect of industrial waste on the environment, Russian Journal of Genetics, 2005, 41, 608-612.
Accumulation, storage and distribution of molybdenum in animals
In experimental animals given lethal or near lethal doses, however administered, of molybdenum trioxide, calcium molybdate or ammonium heptamolybdate the rate of excretion of molybdenum was less than the rate of absorption [Underwood, 1962; Kolomiitseva et al., 1968; Schroeder et al., 1970]. The amount accumulating in the tissues increased with increasing size and number of doses. After administration of molybdenum had ceased the molybdenum content of the tissues dropped quite rapidly. For example, in guinea pigs exposed to molybdenum trioxide for eight days total molybdenum had dropped to the control value four days after the dose had ceased. [Fairhall et al., 1945] The percentage drop for bone was least so it appears that there is some preferential storage of molybdenum in bone. In general absorption and excretion of molybdenum are rapid and a high proportion (ca 95%) of molybdenum added to the diet is excreted and rather little molybdenum is stored in the tissues. Additional studies involving rats gave the following breakdown of absorbing organs; 3.6% stomach, 9.5% duodenum and 8.2 % in the ileum [van Campen and Mitchell, 1965]. However, as stated, many other groups have found that the process of absorption and retention is dependent on dose, mode of administration and the age of the experimental animal.
Underwood, E. J.,Trace Elements in Human and Animal Nutrition, Academic Press, London, 2nd Ed., 1962, 100.
Kolomiitseva, M. G., Polonskaya, M. N. and Osipov, G. K.,Mikroelem. Sel. Khoz. Med., 1968, 4, 183
Schroeder, H. A., Balassa, J. J.and Tipton,I. H., J. Chronic Diseases, 1970, 23, 481.
Fairhall, L. T., Dunn, R. C., Sharpless, N. E. and Pritchard, E. A., U. S. Public Health Bull., 1945, 293, 1.
Van Campen, D. R., Mitchell, E. A. (1965), J. Nutr., 86, 120-124.
In lactating goats, 99MoO3 , administered orally was found in skeleton, liver, skin, muscles, blood, kidney, ovary and hair 4 days later. Molybdenum was also detected in the milk of goats fed molybdenum trioxide [Anke et al., 1971].
The concentration of molybdenum in cows' milk increased after daily feeding of 500 mg ammonium molybdate [Mills and Davis, 1987].
Fairhall, L. T., Dunn, R. C., Sharpless, N. E. and Pritchard, E. A., U. S. Public Health Bull., 1945, 293, 1.
Venugopal, B. and Luckey, T. D., Metal Toxicity in Mammals, 1978, Vol. 2, Chemical Toxicity of Metals and Metalloids, Plenum Press, New York.
Anke, M., Hennig, A., Dieltrich, M., Hoffmann, G., Wicke, G. and Pflug, D.,Arch. Tierernaehr., 1971, 21, 205.
Mills, C. F. and Davis, G. K., in :Trace elements in Human and Animal Nutritution, Metrz, W., ed., 1987, 429, Academic Press, New York.
Fischer rats given subcutaneous injections of N-methyl-N-benzylnitrosamine and fed dietary sodium molybdate (2 ppm) had increased molybdenum concentrations in the esophagus, forestomach, blood serum, and liver. Xanthine oxidase activities were also increased in the esophagus and forestomach, but not in the liver [Komada et al., 1990]. Radioactivity was detected in the liver, bone, heart, lungs, blood, and kidneys 2.5 hours after rats were fed a single dose (13.34 mg) of 99Mo. The concentrations of radioactivity were higher in the intestine, kidney, and bone than in other tissues 51 hours after dosing. It was estimated that 35% of the administered dose was absorbed [Neilands et al., 1948].
Komada, H., Kise, Y., Nakagawa, M., Yamamura, M., Hioki, K. and Yamamoto, M., Cancer Res., 1990, 50, 2418.
Neilands, J. B., Strong, F. M. and Elvehjem, C. A., J. Biol. Chem., 1948, 172, 431.
In dogs receiving 99Mo by injection, molybdenum was selectively concentrated in the liver, kidneys and endocrine glands (pancreas, pituitary, adrenal and thyroid). The brain, bone marrow and fat contained neglible amounts of the injected molybdenum [Clayton and Clayton, 1981].
Clayton, G. D. and Clayton, F. E., eds, Patty's Industrial Hygiene and Toxicology, 3rd Ed., 1981, 2A, 1493. John Wiley and Sons, New York.
The absorption, tissue distribution and excretion patterns of molybdenum in rabbits are similar to those found for other species as described above. Increased molybdenum intake by experimental animals has been shown to increase tissue levels of xanthine oxidase; liver, intestine and kidney; [Luo et al., 1983].
Luo, X. -M., Wei, H. -J. and Yang, S. P., J. Nat. Cancer Inst.,1983, 71, 75.
Exposure to molybdenum trioxide dust (30 mg/m3 ) for 5.5 months increased serum and urinary ascorbic acid levels in rabbits but no similar effects occurred in rats [Lukashev and Shishkova, 1971].
Lukashev, A. A. and Shishkova, Tr. Nauch.-Issled. Inst. Kraev. Patol. Alma Ata, 1971, 22, 152, 175, 191.
Absorption of molybdenum experimental animals
In animals (guinea pigs, rabbits, rats, sheep) water-soluble molybdenum compounds and also molybdenum trioxide and calcium molybdate, but not molybdenum disulfide, are readily absorbed from the intestinal tract and lungs. Concentrations of molybdenum in the tissues, bones, and blood rise rapidly after administration of molybdenum compounds [Rosoff and Spencer, 1964].
Rosoff, B. and Spencer, H., Nature, 1964, 202, 410.
Molybdenum Retention in Animals
|
Animal |
Administration |
Amount given /mg |
Form |
Time /h |
Percent remaining |
|
Rat |
Oral |
13.3 |
Mo |
51 |
3 |
|
Calf |
Oral |
16.8 |
MoO3 |
288 |
21 |
|
Calf |
Intra-venous |
11.0 |
MoO3 |
96 |
52 |
|
Goat |
Oral |
- |
Mo |
- |
35 |
Neilands, J. B., Strong, F. M., and Elvehjem, C. A., J . Biol. Chem., 1948, 172, 431.
Comar. C. L., Singer, L., and Davis, G. K., J. Biol. Chem., 1980, 1949, 913.
Excretion of molybdenum in animals
With animals the concentration of molybdenum in the urine and faeces rises rapidly after administration of molybdenum trioxide and molybdates. Molybdenum is excreted mainly in the urine probably as the molybdate anion. With human subjects injected intravenously with a single tracer dose of 99Mo, after five days 16.6-27.2% of the 99Mo had been excreted in the urine and only 1-6.8% in the faeces [Rosoff and Spencer, 1964]. It has been estimated that the average excretion of molybdenum by humans is about 50-70 microg per day [Friberg and Lener, 1986]. The amount of molybdenum excreted and the route are affected by sulfate (added to, or as part of, the diet). For cattle, sheep and rats the total amount of molybdenum excreted and the proportion in the urine increases with increasing sulfate in the diet [Dick, 1969]. A study using radiomolybdenum to trace the excretion process in cattle found that the biological half-life of molybdenum was 19.9 ± 1.4 h [Robinson et al., 1968].
Rosoff, B. and Spencer, H., Nature, 1964, 202, 410.
Friberg, L. and Lener, J., in: Handbook of Toxicology of Metals, Friberg L. et al. (eds.), 2nd Ed., 1986, II, 446. Elsevier Science Publishers, Amsterdam.
Dick, A. T., Outlook Agr., 1969, 6, 14.
Robinson, G. A., Valli, V. E. O., McSherry, B. J. and Pepino, A. M., Can. J. Physiol. Pharmacol., 1968, 47, 343.
Molybdenum deficiency in animals
A deficiency of molybdenum is most likely to occur on acid, freely drained soils rich in iron oxides. The plants with levels of molybdenum toxic for livestock most often grow on humous soils and those with impeded drainage. It was the knowledge of the metabolic interrelationships of molybdenum, copper, and sulfur that emphasized its biological importance. A number of reviews have addressed aspects of this subject [Mills and Davis, 1987; Clarke and Clarke, 1975; Bremner, 1979; National Research Council 9, 1980; Spiro, 1985; Coughlin, 1980; Abumrad, 1984; Moura and Xavier, 1978; Kaul et al., 1985; Allen and Gawthorne, 1986; Rajagopalan, 1987].
Mills, C. F. and Davis, G. K., in: Trace elements in Human and Animal Nutrition, Metrz, W., (ed.), 5th Ed., 1987, 429. Academic Press, New York.
Clarke, E. G. C. and Clarke M. L., Molybdenum in: Veterinary Toxicology, 1975, 86. Wilkins & Wilkins, Baltimore, Maryland.
Bremner, I., Toxicity of Cadmium, Zinc and Molybdenum and Their Effects on Copper Metabolism. Proc. Nutr. Soc., 1979, 38, 235.
National Research Council, Molybdenum, in: Mineral Tolerance of Domestic Animals,1980, 9, 328. National Academy of Sciences, Washington, D.C.
Spiro, T. G. (ed.), Molybdenum Enzymes , 1985, John Wiley & Sons, New York.
Coughlin, M. P., Molybdenum and Molybdenum Containing Enzymes, 1980, Pergamon Press, Oxford.
Abumrad, N. N., Bull. N.Y. Acad. Med., 1984, 60, 163.
Moura, J. J. G. and Xavier, A. V., in: Williams, R. J. P. and DeSilva, J. J. R. F. (eds.), Trends in Bioinorganic Chemistry, 1978, 79. Academic Press, New York.
Kaul, Bh. B., Enemark, J. H., Merbs, S. L. and Spence, J. T., J. Am. Chem. Soc., 1985, 107, 2885.
Allen, J. D. and Gawthorne, J. M., J. Inorg. Biochem., 1986, 27, 95.
Rajagopalan, K. R., Molybdenum - An Essential Trace Element. Nutr. Rev., 1987, 45, 321.
It is possible to produce a deficiency of molybdenum in rats by the inclusion of 45 or 94 mg of tungsten, as tungstate, per kilogram of diet [National Research Council 9, 1980]. The consumption of low molybdenum forage has been associated with xanthine calculi in sheep [Askew, 1958]. Clinical symptoms or irritability leading to coma, tachycardia, tachypnea and night blindness in a human patient receiving total parental nutrition were completely eliminated by supplementation with 300 microg of ammonium molybdate per day providing evidence for an essential role of molybdenum in human nutrition [Abumrad et al., 1981]. Diets low in molybdenum fed to goats [ Anke et al., 1978] and to chicks [Payne, 1978] resulted in detrimental effects associated with reproduction. Goats had poor conception rates and poor fetal survival. Chicks suffered high embryonic mortality and abnormal growth and development.
National Research Council 9, 1980
Askew, H. O., N.Z. J. Agric. Res., 1958, 1, 447.
Abumrad, N. N., Schneider, A. J., Steel, D. and Rogers, L. S., Am. J. Clin. Nutr., 1981, 34, 2551.
Anke, M., Grün, M., Partschefeld, M. and Groppel, B., in: Trace Element Metabolism in Man and Animals, Kirchgessner, M. (ed.), 1978, 3, 203. Institut für Ernährungsphysiologie, Technische Universität München, Freising-Weihenstephan.
Payne, C. G. and Bains, B. S., Vet. Rec., 1975, 97, 436.
Signs of molybdenum deficiency due to lower molybdenum intakes in food were reported from New Zealand where lambs raised in areas with lower molybdenum concentrations in the soil showed symptoms of renal lithiasis. The calculi detected in these animals were made up of xanthine. This pathologic condition which can be considerably aggravated by concurrent deficiency of proteins is called xanthine disease.
In Australia and the USA a syndrome was described in chicks which was characterised by loss of feathers, impaired ossification of long bones and by changes in the cartilage of joints resulting in complete immobilization. The link with molybdenum deficiency was clearly demonstrated by a rapid disappearence of these symptoms after the addition of 0.5 - 2.5 mg/kg of molybdenum in subsequent feed [Bains and McKenzie, 1975; Payne and Bains, 1975].
Bains, B. S. and McKenzie, M. A., Aust. Vet. J., 1975, 51, 364.
Payne, C. G., in: Trace Element Metabolism in Man and Animals, Kirchgessner, M. (ed.), 1978, 3, 1515. Institut für Ernährungsphysiologie, Technische Universität München, Freising-Weihenstephan.
Molybdenum Retention in Animals
|
Animal |
Administration |
Amount given /mg |
As |
Time /h |
Percent remaining |
|
Rat |
Oral |
13.3 |
Mo |
51 |
3 |
|
Calf |
Oral |
16.8 |
MoO3 |
288 |
21 |
|
Calf |
Intra- venous |
11.0 |
MoO3 |
96 |
52 |
|
Goat |
Oral |
- |
Mo |
- |
35 |