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Assessment of molybdenum toxicity in humans
1Département de médecine du travail et d'hygiène du milieu, Faculté de médecine, Université de Montréal, Québec, Canada. Vyskocia@ere.Umontreal.ca
Abstract:
In an attempt to define a tolerable daily intake (TDI) for molybdenum based on a toxicological risk analysis approach, a large literature survey was conducted. In man, absorption of molybdenum after oral intake is in the range of 28-77% and urinary excretion is 17-80% of the total dose. A low order of toxicity of molybdenum compounds has been observed in humans. However, with the available data, it is not possible to calculate any dose-response or dose-effect relationships. Because molybdenum toxicity is associated with copper intake or depleted copper stores in the body, humans who have an inadequate intake of dietary copper or some dysfunction in their copper metabolism that makes them copper-deficient could be at greater risk of molybdenum toxicity. In the absence of relevant human studies, animal studies were evaluated for the derivation of the TDI. Effects of Mo on reproduction and foetal development were found to be critical effects observed in rats and mice. A dose-response relationship was observed in a study by Fungwe et al., with a 'no observed adverse effect' level (NOAEL) and a 'lowest observed adverse effect' level (LOAEL) of 0.9 and 1.6 mg Mo kg(-1) day(-1), respectively. Applying uncertainty factors of 10 for intraspecies and 10 for interspecies differences to the NOAEL, a TDI of 0.009 mg Mo kg(-1) day(-1) was calculated. The TDI is given a medium confidence rating. This TDI is more than double the upper limit of adequate intake for adolescents and adults that was derived from the Mo content of the average diet in the USA.
Insights
A tolerable daily intake (TDI) for molybdenum was established using toxicological data. Molybdenum toxicity is linked to copper levels, and the new TDI is higher than current adequate intake levels.
Area of Science:
- Toxicology
- Nutritional Science
- Risk Assessment
Background:
- Molybdenum (Mo) absorption and excretion in humans vary significantly.
- Human molybdenum toxicity is generally low but can be exacerbated by copper deficiency.
- Dose-response data for human molybdenum exposure is limited.
Purpose of the Study:
- To establish a tolerable daily intake (TDI) for molybdenum using a toxicological risk analysis.
- To evaluate available human and animal data for molybdenum's toxicological effects.
- To determine safe molybdenum intake levels considering potential risks.
Main Methods:
- Conducted a comprehensive literature survey on molybdenum toxicity.
- Evaluated animal studies, specifically focusing on reproductive and developmental effects in rats and mice.
- Calculated the TDI by applying uncertainty factors to the NOAEL from animal studies.
Main Results:
- Reproductive and foetal development effects were identified as critical endpoints in animal studies.
- A NOAEL of 0.9 mg Mo kg(-1) day(-1) was determined from animal data.
- A TDI of 0.009 mg Mo kg(-1) day(-1) was calculated with medium confidence.
Conclusions:
- The calculated TDI for molybdenum is significantly higher than the adequate intake levels derived from average dietary content in the USA.
- Copper status is a critical factor influencing molybdenum toxicity risk in humans.
- Further research may be needed to refine molybdenum TDI, especially concerning human copper metabolism.