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<pre>Magnesium carbonate
(CAS No: 546-93-0)
Health-based Reassessment of Administrative Occupational Exposure Limits
Committee on Updating of Occupational Exposure Limits,
a committee of the Health Council of the Netherlands
No. 2000/15OSH/084, The Hague, 22 October 2003
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<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Magnesium carbonate; Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of the
Netherlands, 2003; 2000/15OSH/2003.
all rights reserved
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      magnesium carbonate by the Committee on Updating of Occupational Exposure
      Limits, a committee of the Health Council of the Netherlands. The first draft of
      this document was prepared by MA Maclaine Pont, M.Sc. (Wageningen
      University and Research Centre, Wageningen, the Netherlands).
           In May 2000, literature was searched in the databases Medline, Toxline, and
      Chemical Abstracts, starting from 1981, 1966, and 1937, and using the following
      key words: magnesium carbonate; magnesite; carbonic acid, compounds,
      magnesium salt (1:1); 546-93-0; or 13717-00-5. The final literature search was
      carried out in Toxline and Medline in January 2003.
           In April 2003, the President of the Health Council released a draft of the
      document for public review. The committee received no comments.
2     Identity
      name                      :  magnesium carbonate
      synonyms                  :  magnesium (II) carbonate; carbonate magnesium;
                                   carbonic acid, magnesium salt (1:1); magnesite
      molecular formula         :  MgCO3
      structural formula        :  -
      CAS number                :  546-93-0
      Data from ACG99, NLM02.
3     Physical and chemical properties
      molecular weight               :   84.31
      boiling point                  :   900oC (liberating CO2)
      melting point                  :   350oC (decomposes)
      flash point                    :   inflammable
      vapour pressure                :   not available
      solubility in water            :   insoluble (at 20oC: 0.01 g/100 mL)
      log P                          :   -2.12
            octanol/water
      conversion factors             :   not applicable
      Data from ACG99, Lid 99, NLM02, http://esc.syrres.com.
084-3 Magnesium carbonate
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<pre>      Magnesium carbonate consists of odourless, white hexagonal crystals. It occurs
      naturally as the mineral magnesite, which is a white, yellowish, greyish-white, or
      brown crystalline solid, and as 3 hydrates: barringtonite (MgCO3.2H2O),
      landsfordite (MgCO3.5H2O), and nesquehonite (MgCO3.3H2O). In addition,
      there is a series of basic magnesium carbonates (Magnesia alba), having the
      general formula: xMgCO3.yMg(OH)2.zH2O (Bel94, Bud96, Cop81, Lid99).
4     Uses
      Magnesite is used to make various grades of magnesium oxide, to produce
      carbon dioxide and refractories, as an additive to make free-running table salt, as
      a bulking compound in powder formulations, and as an antacid (ACG99).
      Magnesium carbonate is used as a filler for paper, in cosmetics and fire-resistant
      and insulating materials, and for clarifying drinking water. Magnesium carbonate
      boiled in water forms magnesia. Magnesia alba is used as an antacid and as a
      laxative (Bel94).
          In 1985, the Food and Drug Administration of the USA affirmed in their final
      rule that certain magnesium salts, among which magnesium carbonate, are
      generally recognised as safe (GRAS) for use as direct human food ingredients
      (FDA85).
5     Biotransformation and kinetics
      The committee did not find data on the toxicokinetics of magnesium carbonate.
6     Effects and mechanism of action
      Human data
      Magnesium is essential to both plants and animals. The body of an average adult
      contains about 25 g of magnesium. Magnesium is present in many foods, such as
      meats, cereals, vegetables, and milk. The average adult ingests about 300 mg of
      magnesium per day. Magnesium deficiency results in weakness, dizziness, and
      convulsions (Bel94). The daily requirement for adults is 2-3 mg (WHO81).
          Magnesium is a normal constituent of human blood, being present at 1.6-2.2
      meq/L. When serum magnesium reaches 3-4 meq/L, signs of central nervous
      sytem depression, loss of reflexes, muscular tone, and power, hypotension, and
      bradycardia may appear. Death in cardiac arrest and/or respiratory paralysis can
      occur when serum magnesium reaches 10-15 meq/L (ACG99).
084-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>           Only a few epidemiological studies and findings of clinical investigations of
      magnesite-industry workers have been reported so far. The majority is written in
      Slovakian and published as proceedings of a conference. Reichrtová has
      summarised these data. A combined effect of MgCO3 dust in mines and MgO
      dust in the environment has been described with respect to an increasing
      incidence of chronic bronchitis. A significant increase in the incidence of
      duodenal and gastric ulcers was found among magnesite-industry workers as a
      function of exposure duration. It is assumed that inhaled dust is partially ingested
      and thus finds its way to the digestive tract. Among workers involved in MgO
      production from magnesite, an approximately threefold increase was found in
      serum magnesium, incidence of pulmonary emphysema and chronic bronchitis,
      inflammation of nasal and ocular mucus, fatigue, and headache. In another study,
      impairment of upper airways and hearing was reported among magnesite-
      industry workers (Rei92). In other reports presented by ACGIH, cases of
      pneumoconiosis were document amongst others in a group of workers in a
      magnesite plant with 6 to 20 years of employment. Further, it was reported that
      complaints of coughing were rare among magnesite workers. The severity of the
      pneumoconiosis and complaints of coughing were found to be dependent on the
      crystalline silica content or asbestos content of the dust (ACG99).
      Animal data
      Magnesium carbonate was not irritating when tested in rabbits according to EC
      and French directives (Gau94). In evaluating alternative in vitro methods for
      screening eye irritancy, magnesium carbonate was concluded to be not to mildly
      irritating and not irritating in the bovine corneal opacity and permeability
      (BCOP) and hen's egg test-chorioallantoic membrane (HET-CAM) assay,
      respectively (Gau94, Gil96).
           A single intratracheal instillation of 1 mL of a 7.5% suspension of
      magnesium carbonate (75 mg MgCO3) in rats caused intense acute inflammatory
      reactions (no further data presented) (Hus52).
           After a single intraperitoneal injection, magnesium carbonate did not induce
      adhesion of the abdominal wall in female Wistar rats at doses up to 100 mg. At
      doses up to 500 mg, there were no ascites or deposits of powder adherent to
      viscera. The authors concluded that magnesium carbonate is one of the least
      harmful powders out of 7 tested for use as dusting powder in condoms or surgical
      gloves (Kan92).
084-5 Magnesium carbonate
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<pre>      Carcinogenicity
      Groups of male Fischer 344 rats were injected intrarenally with either vehicle
      (n=20), 2 doses of 5 mg of Ni3S2 (nickel subsulphide) (n=40), 2 doses of 6.2 mg
      of 4MgCO3.Mg(OH)2.nH2O (magnesium basic carbonate, MgCarb) (n=20), or 2
      doses of Ni3S2 plus MgCarb (n=20). After 109 weeks, no kidney tumours were
      found in the MgCarb group. Ni3S2 alone induced local renal tumours in 62.5% of
      the rats, with the first tumour appearing at week 30 after the injections. Ni3S2
      carcinogenesis was strongly inhibited by MgCarb. The addition delayed the
      onset of renal tumours by 44 weeks and lowered the final yield of tumours to
      20%. The authors did not have an explanation for the mode of action of
      magnesium (Kas94).
          A similar experiment was performed by intramuscularly injecting male
      Fischer 344 rats with either 2.5 mg Ni3S2, or 6.1 mg MgCarb, or both doses
      combined, or with vehicle (in all cases: n=20). After 79 weeks, no sarcomas in
      the kidneys or metastases in lungs, kidneys, or other organs were found in the
      MgCarb group. In the Ni3S2 group, 100% of the animals had tumours,
      predominantly rhabdomyosarcomas. MgCarb inhibited the carcinogenicity of
      Ni3S2 in a dose-related manner. The final incidence of sarcomas decreased from
      100% to 55%, and the appearance of first tumours was delayed from 25 to 39
      weeks (Kas87).
          Groups of 20 male F344 rats were given 5% L-ascorbic acid (AsA) (i.e.,
      2800 mg/kg/day*, or 3% MgCO3 (i.e., 1500 mg/kg/day), or 5% AsA plus 3%
      MgCO3 (i.e., 3200 and 1900 mg/kg/day, respectively), or none of these
      compounds via the diet for 32 weeks, following a 4-week pre-treatment with
      0.05% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) via the drinking water.
      Groups of 5 male F344 rats received also AsA, MgCO3, or AsA plus MgCO3 via
      the food without pre-treatment with BBN (negative control groups). There was
      no increase in absolute urinary bladder weight or in the incidence of bladder
      papillary or nodular hyperplasia or papillomas or carcinomas (Fuk87).
      Mutagenicity and genotoxicity
      Magnesium carbonate was negative when tested - probably without metabolic
      activation - at only one concentration (50 mM) in a gene mutation assay using S.
      typhimurium strain TA102 (Cro96).
*     Calculated from an assumed mean body weight of 300 mg and data on average food intake presented in Fuk87.
084-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>          Magnesium carbonate did not induce micronuclei in CHO cells or DNA-
      protein crosslinks in Balb/3T3 cells (concentration range: 0.6-2.4 µg/mL).
      Magnesium carbonate decreased the nickel-induced genotoxicity in CHO and
      Balb/3T3 cells (Hon97).
      Reproduction toxicity
      The committee did not find data on the potential reproduction toxicity of
      magnesium carbonate.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for magnesium
      carbonate in the Netherlands is 10 mg/m3, 8-hour TWA, as inhalable dust.
          Existing occupational exposure limits for magnesium carbonate in some
      European countries and in the USA are summarised in the annex.
8     Assessment of health hazard
      Magnesium is essential to both plants and animals, and recognised as safe for
      oral use as a direct human food ingredient, with a daily requirement for adults of
      2-3 mg. Occupational inhalation exposure to unknown levels of, very probably,
      combined exposures of magnesium carbonate and magnesium oxide were
      reported to induce bronchitis, pulmonary emphysema, pneumoconiosis, nasal
      and ocular inflammation, fatigue, and headache in magnesite workers. In
      addition, co-exposure to crystalline silica and asbestos may have occurred as
      well, and in some studies, incidence and severity of the symptoms seemed to
      depend on the crystalline silica content or asbestos content of the dust. Therefore,
      the committee is of the opinion that the human data cannot be used for the
      assessment of the health effects of magnesium carbonate per se.
          In long-term studies with rats, basic magnesium carbonate did not induce
      renal tumours or metastases in any organ; the compound inhibited the
      carcinogenic activity of nickel subsulphide (Ni3S2) in a dose-related manner
      (Kas87, Kas94). Magnesium carbonate did not affect the bladder of rats, after
      dosing via the food for 32 weeks, with an estimated intake of 1500 mg/kg bw/
      day (Fuk87).
          The committee considers the lungs to be the target organ for toxicity.
084-7 Magnesium carbonate
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<pre>       Although the committee considers the toxicological database on magnesium
       carbonate too poor to justify recommendation of a health-based occupational
       exposure limit, the committee is of the opinion that the current occupational
       exposure limits of 5 and 10 mg/m3 for respirable and inhalable dust, respectively,
       are acceptable for regulation of magnesium carbonate exposure.
       In the presence of asbestos and crystalline silica, the legally binding MAC values
       of those substances have to be adhered to.
       References
ACG99  American Conference of Governmental Industrial Hygienists (ACGIH). Magnesite. In: TLVs® and
       other occupational exposure values - 1999. [CD-ROM]. Cincinnati OH, USA: ACGIH®, Inc, 1999.
ACG03a American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2003. Cincinnati OH, USA: ACGIH®, Inc, 2003: 78.
ACG03b American Conference of Governmental Industrial Hygienists (ACGIH). 2003 TLVs® and BEIs®
       based on the documentation of the Threshold Limit Values for chemical substances and physical
       agents & Biological Exposure Indices. Cincinnati OH, USA: ACGIH®, Inc, 2003: 37.
Arb02  Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
       2002; At-vejledning C.0.1.
Bel94  Beliles RP. Magnesium. In: Clayton GD, Clayton FE, ed. Toxicology. 4th ed. J Wiley & Sons, New
       York, USA, 1994: 2097-106 (Patty's industrial hygiene and toxicology; Vol II; Pt C; Section 20).
Bud96  Budavari S, O'Neill MJ, Smith A, et al, eds. The Merck index. An encyclopedia of chemicals, drugs,
       and biologicals. 12th ed. Whitehouse Station NJ, USA: Merck & Co, 1996: 969.
Cop81  Copp AN, Wardle R. Magnesium compounds. In: Grayson M, ed. Kirk-Othmer Encyclopedia of
       chemical technology. New York, USA: J. Wiley & Sons, 1981; 14: 618-21.
Cro96  Della Croce C, Ambrosini C, Cini M, et al. Effect of magnesium salts on mitotic gene conversion and
       point mutation induced by hydrogen peroxide in yeast Saccharomyces cerevisiae. Med Biol Environ
       1996; 24: 51-9.
DFG02  Deutsche Forschungsgemeinschaft (DFG): Commission for the Investigation of Health Hazards of
       Chemical Compounds in the Work Area. List of MAK and BAT values 2002. Maximum
       concentrations and biological tolerance values at the workplace. Weinheim, FRG: Wiley-VCH, 2002;
       rep no 38.
EC03   European Commission: Directorate General of Employment and Social Affairs. Occupational
       exposure limits (OELs). http://europe.eu.int/comm/employment_social/h&s/areas/oels_en.htm.
FDA85  US Food and Drug Administration (FDA). GRAS status of magnesium carbonate, magnesium
       chloride, magnesium hydroxide, magnesium oxide, magnesium phosphate, magnesium stearate, and
       magnesium sulfate. Fed Reg 1985; 50: 13557-60.
084-8  Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>Fuk87 Fukushima S, Shibata M, Shirai T, et al. Promotion by L-ascorbic acid of urinary bladder
      carcinogenesis in rats under conditions of increased urinary potassium ion concentration and pH.
      Cancer Res 1987; 47: 4821-4.
Gau94 Gautheron P, Giroux J, Cottin M, et al. Interlaboratory assessment of the bovine corneal opacity and
      permeability (BCOP) assay. Toxicol in Vitro 1994; 8: 381-92.
Gil96 Gilleron L, Coecke S, Sysmans M, et al. Evaluation of a modified HET-CAM assay as a screening
      test for eye irritancy. Toxicol in Vitro 1996; 10: 431-46.
Hon97 Hong YC, Paik SR, Lee HK, et al. Magnesium inhibits nickel-induced genotoxicity and formation of
      reactive oxygen. Environ Health Perspect 1997; 105: 744-8.
HSE02 Health and Safety Executive (HSE). EH40/2002. Occupational Exposure Limits 2002. Sudbury
      (Suffolk), England: HSE Books, 2002: 20.
Hus52 Huston J Jr, Wallach DP, Cunningham GJ. Pulmonary reaction to barium sulfate in rats. Am Med
      Assoc Arch Pathol 1952; 54: 430-8.
Kan92 Kang N, Griffin D, Ellis H. The pathological effects of glove and condom dusting powders. J Appl
      Toxicol 1992; 12: 443-9.
Kas87 Kasprzak KS, Ward JM, Poirier LA, et al. Nickel - magnesium interactions in carcinogenesis: dose
      effects and involvement of natural killer cells. Carcinogenesis 1987; 8: 1005-11.
Kas94 Kasprzak KS, Diwan BA, Rice JM. Iron accelerates while magnesium inhibits nickel-induced
      carcinogenesis in the rat kidney. Toxicology 1994; 90: 129-40.
Lid99 Lide DR, ed. CRC Handbook of chemistry and physics. 80th ed. Boca Raton FL, USA: CRC Press,
      1999; 4-68.
NLM02 US National Library of Medicine (NLM), ed. Magnesium carbonate. In: Hazardous Substances Data
      Bank (HSDB) (last revision date magnesium carbonate file: May 13, 2002; last review date:
      September 29, 1994); http://toxnet.nlm.nih.gov.
Rei92 Reichrtová E, Takác L. Issues related to dust aerosols in the magnesite industry. I. Chamber exposure.
      J Hyg Epidemiol Microbiol Immunol 1992; 36: 235-44.
Swe00 Swedish National Board of Occupational Safety and Health. Occupational exposure limit values and
      measures against air contaminants. Solna, Sweden: National Board of Occupational Safety and
      Health, 2000; Ordinance AFS 2000:3.
SZW03 Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2003. The Hague,
      the Netherlands: Sdu, Servicecentrum Uitgevers, 2003: 33.
TRG00 TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArbBl
      2000; 2.
WHO81 World Health Organization: International Programme on Chemical Safety (WHO/IPCS). Manganese.
      Geneva, Switzerland: WHO, 1981; Environmental Health Criteria 17.
084-9 Magnesium carbonate
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<pre>              Annex
Occupational exposure limits for magnesium carbonate in various countries.
country                                    occupational           time-weighted          type of        notea  referenceb
- organisation                             exposure limit         average                exposure limit
                                           ppm       mg/m3
the Netherlands
- Ministry of Social Affairs and           -         10c          8h                     administrative        SZW03
Employment
Germany
- AGS                                      -         -                                                         TRG00
- DFG MAK-Kommission                       -         -                                                         DFG02
Great Britain
- HSE                                      -         10c; 4d      8h                     OES                   HSE02
Sweden                                     -         -                                                         Swe00
Denmark                                    -         -                                                         Arb02
USA
- ACGIH                                    -         10e          8h                     TLV                   ACG03b
- OSHA                                     -         15c; 5d      15 min                 PEL                   ACG03a
- NIOSH                                    -         10c; 5d      8h                     REL                   ACG03a
European Union
- SCOEL                                    -         -                                                         EC03
a
     S = skin notation, which means that skin absorption may contribute considerably to body burden; sens = substance can
     cause sensitisation.
b
     Reference to the most recent official publication of occupational exposure limits.
c
     As (total) inhalable dust.
d
     As respirable dust.
e
     The value is for particulate matter containing no asbestos and <1% crystalline silica.
084-10        Health-based Reassessment of Administrative Occupational Exposure Limits
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