MANGANESE & HEALTH: A BALANCE OF STORIES November 2014 1
Overview 2. Analysis of Literature on Carcinogenicity & Mutagenicity 1. Uses of inorganic Mn substances 3. Research to better understand Carcinogenicity & Mutagenicity potential 5. Research on reprotoxicity to put an end to the story 4. Reprotoxicity & Authorities understanding November2014 2
Uses of Inorganic Mn-based substances Introduction: One vital feature of manganese, which is not widely appreciated, is its role as an essential element. Outside this role are other unique properties necessary for the production of numerous applications which impact on our daily lives as consumers. Steel making: Mn s ability to combine with sulphur and its powerful deoxidation capacity make it a vital component of steel, giving it the necessary hardness and strength Portal Batteries Manganese in the form of manganese dioxide functions as an electron acceptor in alkaline batteries Aluminum beverage cans: Manganese plays an essential role in the absorption of impurities which then increases resistance against corrosion in aluminum cans Fertilizers: Manganese is a micronutrient necessary for plant metabolism. In high ph soils, organic soils, and sandy soils Mn- containing fertilizers are required IMnI 3
2. Analysis of literature on Carcinogenicity & Mutagenicity The reviewed published literature on carcinogenicity & genotoxicity potential of inorganic Mn (????) Concluded that: Available occupational & environmental epidemiological evidence is equivocal as to whether exposure to inorganic Mn is associated with risk to cancer There is insufficient evidence to indicate that inorganic Mn exposure produces cancer in animals or humans
3. Research to Investigate Carcinogenicity & Mutagenicity potential Of Inorganic Mn substances MnCl2 (1) Study: Ames Test Bacterial reverse mutation assay (Ames test) Looks at gene mutation using Rat Liver cells Conducted to OECD Guideline 471; EU Method B.13/14, US EPA (TSCA) and Japanese Regulatory Authorities guidelines (METI) Results No toxicological increase in the frequency of reverse mutation Non- mutagenic
3. Research to Investigate Carcinogenicity & Mutagenicity potential Of Inorganic Mn substances (2) Study: Mouse Lymphoma Gene mutation To OECD Guideline 476 & GLP guidelines Results: Did not induce any dose related increase in mutant frequency It was considered to be nonmutagenic
3. Research to Investigate Carcinogenicity & Mutagenicity potential Of Inorganic Mn substances (3) Study: Chromosome aberration Mammalian chromosome aberration (cultured human lymphocytes) OECD Guideline 473 & GLP Results: Doses were high enough to cause toxicity to the lymphocytes but did not induce cell aberration Non-clastogenic
3. Research to Investigate Carcinogenicity & Mutagenicity potential Of Inorganic Mn substances (4) *Study: In vivo Micronucleus Mammalian Erythrocytes OECD Guideline 474 & GLP Results: Genotoxicity: negative Female toxicity: no effects Animal no. 23 showed hunched posture at 1 hour post dose observation on Day 1 of the study All other animals were found to be normal throughout the study *Published literature - Streicker MA (2009)
Carcinogenicity & Mutagenicity Results & Conclusions The suite of studies conducted used cells from different genus's rat, mouse, human... The research also investigated different parts of cells e.g. nucleus, chromosome... All studies were conducted to internationally recognised guidelines and sponsored by different organisations The doses were high enough to induce toxicity but in all cases mutagenicity and carcinogenicity effects were not seen Manganese is NOT a Carcinogen or a Mutagen IMnI 9
4. Reprotoxicity & authorities understanding The EU Scientific Committee on Occupational Exposure Limits (SCOEL) commented that that there was little evidence for reproductive or developmental toxicity of inhaled manganese The US Agency for Toxic Substances and Disease Registry (ATSDR) reported that impaired sexual function in men may be one of the earliest clinical manifestations of Mn toxicity... Health Canada s website states that a number of studies have shown that exposure to Mn can cause deleterious effects on the male reproductive system IMnI 10
5. Research on reprotoxicity to put an end to the story Group 1 Group 2 Group 3 Group 4 Animals F0 28M+28F F1 26M+26F F0 28M+28F F1 24+24F F0 28M+28F F1 24M+24F F0 28M+28F F1 25M+25F F0 Target dose (µg/l) Dose period Daily dose duration* Frequency 0 (air) 5 10 20 F0 Approximately 17 weeks F1 Approximately 17 weeks 6 hours Daily F1 F2
Reproductive toxicity Results & conclusions No changes in reproductive organ weights & histology, No effects on sperm quality & quantity, No effects on oestrous cycles, fertility or duration of gestation No decrease in libido for both males & females # of implantation sites, birth weights, litter sizes were normal... Manganese is NOT a REPROTOXICANT Metal Bulletin 12
Take home messages Industry/employers should know the intrinsic properties of the substances they manufacture and/or use Scientists should invest in good and sound science minimizing any potential confounders Regulators should use the latest science and understand information from different kinds of research to make good decisions Workers, communities, NGO s and unions should have a balance of stories to enable then draw their own conclusions Inorganic manganese based substances are NOT carcinogenic, mutagenic or toxic to reproduction Now Go! Tell This Story! IMnI 13
Thank you! Happy to answer any questions!