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Modeling U-shaped dose-response curves for manganese using categorical regression.

Brittany Milton1, Daniel Krewski2, Donald R Mattison3

  • 1Risk Sciences International, 55 Metcalfe Street, Suite 700, K1P 6L5, Ottawa, Canada.

Neurotoxicology
|October 11, 2016
PubMed
Summary

Optimal manganese intake balances essential nutrient needs, preventing adverse effects from deficiency or excess. This study estimates this optimal level using a U-shaped exposure-response model in rats, highlighting the need for human studies.

Keywords:
Categorical regressionDeficiencyExcessManganese toxicityU-shaped dose-response curve

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Area of Science:

  • Nutritional Science
  • Toxicology
  • Biostatistics

Background:

  • Manganese is an essential nutrient with a narrow optimal intake range.
  • Both insufficient and excessive manganese intake can lead to adverse health effects.
  • A U-shaped exposure-response relationship characterizes manganese's impact on health.

Purpose of the Study:

  • To estimate the optimal dietary intake of manganese.
  • To balance the risks associated with manganese deficiency and excess intake.
  • To model the U-shaped exposure-response relationship for manganese.

Main Methods:

  • Conducted a systematic literature review (1930-2013) on manganese deficiency and excess.
  • Created a database of oral manganese toxicity from diverse studies.
  • Standardized toxicological outcomes on an 18-point severity scale and used logistic regression for U-shaped curve modeling.

Main Results:

  • Analyzed data from 6113 rats, establishing a comprehensive manganese toxicity database.
  • The nadir of the U-shaped curve, representing optimal intake, was estimated at 2.70 mg/kg body weight/day (95% CI: 2.51-3.02).
  • Both deficient and excess manganese intake were associated with a 90% probability of adverse events.

Conclusions:

  • The developed manganese database aids in estimating optimal intake by integrating adverse effect data.
  • Further human studies are crucial for validating and applying these findings.
  • Interspecies differences in manganese sensitivity necessitate adjustments for translating rat data to humans.