<b>Bijsluiter</b>. De hyperlink naar het originele document werkt niet meer. Daarom laat Woogle de tekst zien die in dat document stond. Deze tekst kan vreemde foutieve woorden of zinnen bevatten en de opmaak kan verdwenen of veranderd zijn. Dit komt door het zwartlakken van vertrouwelijke informatie of doordat de tekst niet digitaal beschikbaar was en dus ingescand en vervolgens via OCR weer ingelezen is. Voor het originele document, neem contact op met de Woo-contactpersoon van het bestuursorgaan.<br><br>====================================================================== Pagina 1 ======================================================================

<pre>Iron salts, water-soluble
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/102 The Hague, March 30, 2004
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<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Iron salts, water-soluble; Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of the
Netherlands, 2004; 2000/15OSH/102.
all rights reserved
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<pre>1            Introduction
             The present document contains the assessment of the health hazard of water-
             soluble iron salts 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 AAE Wibowo, Ph.D. (Coronel Institute,
             Academic Medical Centre, Amsterdam, the Netherlands).
                 The evaluation of the toxicity of water-soluble iron salts has been based on
             the reviews by Elinder (Eli86) and by the American Conference of
             Governmental Occupational Hygienists (ACGIH) (ACG96). Where relevant, the
             original publications were reviewed and evaluated as will be indicated in the text.
             In addition, literature was retrieved from the databases Medline, Chemical
             Abstracts, Embase (starting from 1966, 1970 and 1988, respectively), and
             HSELINE, NIOSHTIC, CISDOC, and MHIDAS (backwards from 1997) and
             Poltox (Toxline, Cambr Sc Abstr, FSTA) (backwards from 1994), using the
             following key words: ferric chloride, ferric nitrate, ferric sulfate, ferrous
             chloride, ferrous sulfate, 7705-08-0, 10421-48-4, 10028-22-5, 7758-94-3, and
             7720-78-7. The final search was carried out in November 1997.
                 In December 1998, the President of the Health Council released a draft of the
             document for public review. No comments were received.
                 An additional literature search in September 2003 did not result in
             information changing the committee's conclusions.
2            Identity
name                   : ferric chloride  ferric nitrate ferric sulphate  ferrous chloride ferrous sulphate
molecular formula      : FeCl3            Fe(NO3)3       Fe2(SO4)3        FeCl2            FeSO4
CAS number             : 7705-08-0        10421-48-4     10028-22-5       7758-94-3        7720-78-7
102-3        Iron salts, water-soluble
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<pre>3     Physical and chemical properties
                            FeCl3          Fe(NO3)3     Fe2(SO4)3    FeCl2        FeSO4
      molecular weight      162.21         241.87        399.88      127.76       151.91
      boiling pointa        315oC (dec)    <100oC (dec) -            1023oC       -
      melting point         306oC          47oC         -            674oC        -
      flash point           -              -            -            -            -
      vapour pressure       -              -            -            -            -
      solubility            soluble        soluble      soluble      soluble      soluble
      log Poctanol/waterb   0.16           -0.83        -            -0.15        -0.37
      conversion factors    not applicable
      a
           dec = decomposes.
      b
           All estimated values.
      Data from ACG96, http://esc.syrres.com.
      The appearances and odours vary depending on the specific soluble iron salts.
      Ferric chloride is a black-brown solid; ferric nitrate is a pale violet, green, or
      white, odourless solid in a lumpy crystalline form; ferric sulphate is a greyish-
      white or yellow solid in a powder or lumpy crystalline form; ferrous chloride is a
      pale greenish, salt-like crystal or powder; and ferrous sulphate is a greenish or
      yellow solid in fine or lumpy crystalline form (ACG96).
4     Uses
      Ferric chloride is used to treat sewage and industrial waste. It is also used in
      engraving, textiles, and photography, as a disinfectant, and as a food additive.
      Ferric nitrate is used in textile dyeing, tanning, and weighting silk. Ferric
      sulphate is used in pigments, textile dyeing, water treatment, and metal pickling.
      Ferrous chloride is used in textile dyeing, metallurgy, the pharmaceutical
      industry, and sewage treatment. Ferrous sulphate is used as a fertiliser, as a food
      or feed additive, and in herbicides, process engraving, dyeing, and water
      treatment. Ferrous salts (including the most widely used ferrous sulphate USP)
      are used in treatment of iron-deficient anaemia (ACG96). It has been reported
      that iron sulphate is added to cement (in Scandinavian countries) to induce
      precipitation of three-valent chromium, hereby diminishing the incidence of
      contact dermatitis in sensitive subjects (Bru90a, Fre79).
102-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>5     Biotransformation and kinetics
      The comitttee did not find data on the absorption of iron in the respiratory tract.
      It may be surmised that water-soluble iron salts are better absorbed than water-
      insoluble iron compounds. In both humans and animals, iron absorption from the
      digestive tract is adjusted to a fine homeostasis with low iron stores resulting in
      increased absorption and, alternately, sufficient body stores of iron decreasing
      absorption (Eli86). Iron is an essential element in humans. About 2 to 15% of the
      iron ingested via food is absorbed.
           Normally, the human body contains about 3 to 5 g of iron. Two-thirds of this
      amount is found in the blood bound to haemoglobin. Less than 10% of the body
      iron is found in myoglobin and iron-requiring enzymes. Of the remaining
      amounts of iron, about 20 to 30% of the body pool is bound to iron-storage
      proteins: ferritin and haemosiderin. These iron-storage proteins are mainly found
      in liver, bone marrow, and spleen (Eli86).
           The total elimination of iron from the body, under normal conditions, is
      limited to 0.6-1.0 mg/day. Disregarding the non-absorbed iron, about 0.2-0.5
      mg/day of iron is eliminated via the faeces. The mean urinary excretion of iron
      has been reported to be about 0.1-0.3 mg/day. The biological half-time of iron in
      humans is estimated to be 10 to 20 years (Eli86).
6     Effects and mechanism of action
      Human data
      The committee did not find epidemiological data on humans exposed by
      inhalation to water-soluble iron salts. A few cases of acute intoxication induced
      by excessive accidental ingestion of iron compounds have been reported. These
      mostly concern children with fatal endings after taking estimated doses of up to
      15 g of ferrous sulphate (DeC77, Kel68).
           For some years, ferrous sulphate has been added to cement manufactured in
      the Scandinavian countries to prevent sensitisation to and elicitation by chromate
      in cement (Bru90a, Fre79). Bruze et al. investigated whether cement with or
      without ferrous sulphate differed in capacity to elicit allergic patch-test reactions
      in 8 chromate-sensitive subjects. The results showed that no patch-test reactions
      were obtained from a water extract of cement with ferrous iron when
      appropriately buffered (Bru90b).
102-5 Iron salts, water-soluble
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<pre>          Kleinman et al. performed a human volunteer study to investigate the effects
      on pulmonary function and respiratory symptoms of 2-hour inhalation of ferric
      sulphate aerosols. The subjects, 18- to 55-year old, alternately rested and
      exercised on a bicycle ergometer for 15-minute periods during the experiment.
      The number of volunteers was 38, of which 20 subjects with normal pulmonary
      function and no history of lung diseases and 18 subjects diagnosed as asthmatics.
      The nominal concentration was 0.075 mg/m3 ferric sulphate (equivalent to 0.02
      mg Fe/m3), and the mass median aerodynamic diameter of the aerosols was 2 µm
      with a geometric standard deviation of 3 µm. Each subject underwent exposures
      on 2 separate days: a sham exposure to highly purified air at one day and an
      exposure to the test atmosphere at the other day. The 2 days were separated by a
      3-week period. Each subject was treated as his or her own control in the
      subsequent statistical analysis of the data. The results of the experiment showed
      that, on the average, the 2 groups of subjects did not exhibit significant changes
      in total respiratory system resistance, forced expiratory flow/volume
      performance, and single breath nitrogen washout parameters. None of the
      subjects reported more than slight changes in symptoms during exposure. Five
      individuals (one normal and 4 asthmatics) showed small but significant
      decrements in pulmonary function. However, 9 subjects (6 normal and 3
      asthmatics) tended to improve after exposure (Kle81). From this study, the
      committee concludes that the no-observed-adverse-effect level (NOAEL) in
      humans for (instant) effects on the respiratory tract would probably be higher
      than 0.02 mg Fe/m3 of respirable aerosols for a 2-hour exposure period.
      Animal data
      Acute toxicity
      Acute lethal toxicity data for water-soluble iron salts are presented in Table 1.
      Table 1 Acute lethal toxicity data of water-soluble iron salts.
      compound              species          route                    LD50 (mg/kg bw) reference
      FeCl                  mouse            oral                     400             ACG96
           3
                            mouse            oral                     1500            Hop55
                            rabbit           oral                     1200            Hop55
                            guinea pig       oral                     600             Hop55
                            mouse            intraperitoneal          68              ACG96
      FeCl .6H2O            mouse            intraperitoneal          260             ACG96
           3
      Fe(NO3)3.9H2O         rat              oral                     3250            Smy69
      FeCl2                 rat              oral                     600             Hop55
102-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>                          rabbit          oral            1000             Hop55
      FeSO4               rat             oral            3100             Bom00
                          rat             oral            2625             Wea61
                          rata            oral            5500             Whi02
                          mouse           oral            1025             Wea61
                          mouse           intraperitoneal 137              Wea61
                          mouse           intravenous     112              Wea61
                          dog             intravenous     79               Wea61
      FeSO4.7H2O          mouse           oral            4500             Hop55
                          rabbit          oral            3000             Hop55
                          guinea pig      oral            1500             Hop55
                          dog             oral            800              Hop55
      a
          ‘Young’ male animals (age not specified).
      For ferrous sulphate, the oral rat LD50 of 3100 mg/kg bw (see Table 1) was
      determined following administration of doses of 1000, 2000, 2500, 3100, and
      5000 mg/kg bw (n=5/sex/group). Symptoms were seen 1 hour after
      administration and included poor general condition, sedation, growth retardation,
      and piloerection. Deaths occurred from days 1 to 3, necropsy revealing loss of
      gastric mucosal relief and reddened stomach and intestines (partly filled with
      grey-black liquid). Surviving animals were free by day 10 and did not show
      gross lesions at necropsy (Bom00).
      Repeated-dose toxicity
      The effects of subacute ambient exposure to ferric chloride aerosols on the lungs
      of male rabbits were studied by Johansson et al. Groups of 8 rabbits were
      exposed to 0, 1.4, or 3.1 mg Fe/m3, 6 hours/day, 5 days/week, for 2 months. The
      mass median aerodynamic diameter of the aerosols was about 1 µm. After
      exposure, the rabbits were killed. The upper left lung lobe was used for light
      microscopy. The lower lobes were examined by electron microscopy, and the
      remainder was used for phospholipid analysis. The results showed that the high-
      concentration group had significantly higher lung weights that were not observed
      for the low-concentration group. The lungs of the high-concentration group
      showed large nodules of densely packed granular macrophages with brown
      appearance. Sometimes, accumulations of such granular macrophages were
      found in terminal bronchioles as well. Foci of interstitial inflammatory reaction,
      involving mostly lymphocytes, were seen in the high-concentration group.
      Accumulations of normal as well as granular macrophages were observed in the
102-7 Iron salts, water-soluble
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<pre>      alveoli of rabbits of both exposed groups. The control rabbits showed essentially
      normal lung tissue. The volume density of the alveolar type II cells was
      significantly higher in the high-concentration group compared to that of the
      controls. Further studies were performed on the alveolar macrophages obtained
      by lavage. The overall impression was that 96% of the macrophages from the
      controls appeared normal, while one or several changes, e.g., cells with surface-
      lacking protrusions and macrophages with a large number of surfactant-like
      inclusions, were found in about 18 and 48% of the low- and high-concentration
      group, respectively. There was a tendency toward higher oxidative metabolic
      activity in the macrophages from the high-concentration group. The
      concentration of total phospholipids was significantly increased in the high-
      concentration group. There was no significant difference between the groups
      concerning the concentration of phosphatidylcholines in the lung or the
      percentage of 1,2-depalmytoilphosphatidylcholines in the phosphatidylcholines
      (Joh92). From this study, the committee concludes that the lowest-observed-
      adverse-effect level (LOAEL) is 1.4 mg Fe/m3, as respirable aerosols/particles,
      for effects on the lungs of rabbits after subacute inhalation exposure.
          In order to determine appropriate dose levels for a carcinogenicity study,
      Sato et al. administered ferric chloride to rats (Fischer 344; n=10/sex/group) at
      amounts of 0, 0.12, 0.25, 0.5, 1.0, or 2.0% in the drinking water, for 13 weeks.
      Rats were observed daily for clinical signs and mortality, and body weights were
      recorded weekly. At the end of the study, surviving animals were killed for
      haematological, blood chemistry, gross and microscopic examinations. No
      mortality occurred; no information on clinical signs was presented. Water
      consumption was significantly decreased in animals given doses of 0.5% or
      more. No data on food consumption were given. At study termination, body
      weight gain decreases of at least 10% compared with controls were observed in
      male and female animals given 1.0 and 2.0%. In male treated groups, there were
      dose-related increases in serum iron and a significant increase in red blood cell
      counts when compared to controls. Microscopic examination showed pigment
      deposition in several organs/tissues at doses of 0.25% or more (Sat92).
      Carcinogenicity
      In the carcinogenicity study, Sato et al. treated male and female rats (F344; n=50/
      sex/group) with ferric chloride solutions of 0, 0.25, and 0.5% in the drinking
      water, for 2 years, resulting in mean daily doses of 170 and 320 mg/kg bw for
      males and of 188 and 336 mg/kg bw for females. Clinical signs and mortality
      were recorded daily and body weights weekly during the first 13 weeks and once
102-8 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      every 4 weeks thereafter. All rats were subjected to a full post-mortem
      examination and investigated macroscopically and microscopically for the
      occurrence of neoplastic and non-neoplastic lesions. Sato et al. did not present
      findings on signs of toxicity. Apart from a statistically significant increase in
      high-dose males, no differences were seen in final survival rates and mean
      survival time between exposed and control groups. In all exposed groups, there
      were statistically significant, dose-related decreases in final body weights and
      mean daily water intake when compared to controls. Comparison with control
      groups showed that ferric-chloride treatment did not induce statistically
      significant increases in the overall tumour incidence or in the incidence of any
      specific tumour. All tumours observed in this study were similar to those that are
      known to occur spontaneously in this strain of rats. Although various types of
      non-neoplastic lesions were observed in each group, there were no specific
      lesions that could be attributed to treatment to ferric chloride. Although observed
      in the 13-week study at drinking water doses as low as 0.25% (see above), iron
      deposition was not increased in any dose/tissue of the high dose compared with
      the control group at study termination. Sato et al. considered that in this study the
      level of iron overload was too low to increase lipid peroxidation, although this
      was not assessed quantitatively (Sat92). From this study, the committee could
      not establish a NOAEL for chronic oral exposure to ferric chloride, since
      administration of daily doses of 170-188 mg/kg bw, the lowest levels tested,
      caused decreased body weights in male and female rats. The committee
      concludes that ferric chloride was not carcinogenic in rats at doses as high as
      320-336 mg/kg bw/day, the highest levels tested. Since no overt signs of toxicity
      were observed at these levels, the committee cannot draw a definite conclusion
      on the carcinogenicity of ferric chloride.
      Mutagenicity and genotoxicity
      •   In vitro tests:
          • gene mutation assays. Brusick reported in an abstract that ferrous sulphate
             induced reverse mutations in S. typhimurium strains TA1537 and
             TA1538, but not in TA1535. The mutagenic response was most
             pronounced in suspension assays in the presence of metabolic activating
             systems from mouse, rat, guinea pig, monkey, and human liver, while
             variable and weak response were seen in assays without activating systens
             (Bru76). Ishidate et al. reported that ferrous sulphate was negative in a
             bacterial mutation assay using S. typhimurium strains TA92, TA94, TA98,
             TA100, TA1535, and TA 1537 tested with and without induced rat liver
102-9 Iron salts, water-soluble
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<pre>             S9 mix at doses up to 10,000 µg/plate (Ish84). Shimizu et al. found that
             ferric chloride at concentrations of 5 to 5000 µg/plate did not induce
             mutations when tested with or without induced rat liver S9 mix in S.
             typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 and
             E. coli strain WP2 uvrA (Shi85). Ferric chloride and ferrous sulphate were
             both negative when tested with and without metabolic activating systems
             from induced rat and hamster livers in S. typhimurium strains TA97a,
             TA98, TA100, TA102, TA1535, TA1537, and TA1538 (Dun99).
             However, Pagano and Zeiger found that ferrous sulphate induced
             mutations in S. typhimurium TA97 when pre-incubations were done in
             deionised water or HEPES/saline buffer, but not when phosphate buffer
             was used (Pag92).
             In yeast, ferrous sulphate induced reverse mutations and mitotic gene
             conversions at trp 5 and ilv 1 loci in S. cerevisiae strain D7. Ferric
             chloride was negative in this test (Sin83).
             McGregor et al. reported that ferric chloride was negative in the L5178Y
                 +/-
             TK mouse lymphoma cell forward mutation assay. Four experiments
             were conducted, 2 in each activation condition. In none of the
             experiments, there was a mutagenic response without precipitation of
             ferric chloride, precipitation occurring at a concentration of 150 µg/mL
             (McG88). However, in a separate test, Dunkel et al. concluded that ferric
             chloride was positive in this test. A dose-related mutagenic response was
             found in the presence of an induced rat liver S9 mix, with a marked
             increase in cytotoxicity (concentration range tested: 0.2-1.2 µg Fe/mL)
             while no increase in the number of mutants was seen in the absence of
             metabolic activation (concentration range: 309-1030 µg/mL). Ferrous
             sulphate induced a weakly positive response in the absence and a dose-
             related increase in mutant frequency (and a marked increased
             cytotoxicity) in the presence of a S9 mix (concentration ranges: 20.1-201
             and 0.8-2.1 µg/mL, respectively) (Dun99).
             Ogawa et al. reported that ferrous chloride and ferric chloride were
             negative in the D. melanogaster wing spot test (Oga94). Ferrous sulphate
             was listed among compounds that did not give a mutagenic response in
             the Drosophila sex-linked recessive lethal assay (Lee83)
          • cytogenicity assays. Ferrous sulphate (heptahydrate) and ferric chloride
             (hexahydrate), tested at a single dose of 32 µg/mL (i.e., the concentration
             causing 50% growth inhibition of tissue-culture cells), did not cause a
             statistically significant increase in the frequency of sister-chromatid
             exchanges in Don Chinese hamster cells (Ohn82).
102-10 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>               Ferrous sulphate was concluded to be positive in a chromosomal
               aberration assay in a Chinese hamster lung fibroblast cell line, inducing
               increases in the percentage of polyploid cells and of cells with structural
               aberrations (including gaps) at doses of up to 2.5 mg/L (Ish84).
           • other tests. In tests indicative for DNA damage, negative results were
               obtained for ferric chloride, ferric nitrate, and ferric sulphate in the SOS-
               chromotest using E. coli strains PQ37 and PQ35 (Oli87) and for ferric and
               ferrous chloride in the rec assay using B. subtilis strains H17 and M45
               (Nis75).
               Robinson et al. did not find considerable changes in the alkaline sucrose
               profile of Chinese hamster ovary cells treated with a concentration of
               ferrous chloride of 10 µM (the only concentration tested) for 4 hours,
               from which they concluded that no DNA strand breaks had been induced
               (Rob82). Using Syrian hamster embryo cells, ferrous sulphate caused
               increases in the level of DNA damage (OH8dG) and in the incidence of
               DNA strand breaks (comet assay). Co-treatment with antioxidants
               prevented these events, indicating the involvement of reactive oxygen
               species (hydroxy radicals; oxidative stress) (Par02).
       •   In vivo tests:
           Bianchini et al. studied the cytotoxicity and genotoxicity (micronuclei
           induction) of ferrous sulphate and ferric chloride in the gastrointestinal tract
           after single oral (gavage) or intrarectal administration of doses of 0, 10, 32.5,
           and 65 mg/kg bw to female C57BL/6J mice (n=4-10/group). In fasting
           animals, ferric chloride induced a dose-related increase in the frequency of
           (not further specified) nuclear aberrations in the stomach, whereas ferrous
           sulphate was not active. In normally fed animals, no increase in the
           frequency of nuclear aberrations was observed. The effects of the compounds
           on the duodenum were minimal. In fasting animals, a dose-related increase in
           the frequency of nuclear aberrations was found in the colon, with no
           difference between ferrous and ferric compounds. After intrarectal
           administration, an increased incidence of nuclear aberrations was induced
           especially by ferric chloride. The frequency of micronuclei was not increased
           in the stomach, duodenum, or colon (Bia88).
       •   Other tests:
           Casto et al. reported that ferrous chloride and ferrous sulphate at 0.9 to 5.0
           mM enhanced the transformation of Syrian hamster embryo (SHE) cells by a
           simian adeno virus, causing a 2- to 3-fold increase in the absolute number of
102-11 Iron salts, water-soluble
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<pre>           SA7 foci per dish (Cas79). In agreement with these results, Park et al. found
           ferrous sulphate to induce morphological transformation in SHE cells. This
           was prevented by concomitant treatment with antioxidants indicating the
           involvement of reactive oxygen species (hydroxy radicals; oxidative stress)
           (Par02).
       Immunotoxicity
       Ikarashi et al. studied possible immunotoxicity of some metal salts using the
       local lymph node assay (LLNA) on female BALB/c mice. The ability to induce
       lymph node cell proliferation was compared among the metals. This assay is
       known as a predictive test to detect contact allergens. The animals (n=3) received
       25 µL of test solution on the dorsum of each ear repeatedly for 3 consecutive
       days. Four days following the initial application, the mice were killed and the
       draining lymph nodes were excised and pooled per animal. Iron salt (ferrous
       sulphate) failed to induce lymph node proliferation in this assay, in contrast to
       nickel, cobalt, chromium, and copper salts (Ika92a). In another experiment, the
       same authors performed LLNA in mice, guinea pigs, and rats. Iron salt (ferrous
       chloride) failed to induce changes in rats; the experiment was not performed in
       the other species. From these experiments, the authors concluded that water-
       soluble iron salts did not cause allergic contact dermatitis (Ika92b).
           Ban et al. reported that ferrous sulphate and ferric citrate had an
       immunosuppressive effect in an in vitro model for the evaluation of the humoral
       immune response of mice spleen cells to sheep red blood cells (SRBC), the
       response being indicated by the number of antibody-forming cells (AFC) per
       million nucleated cells (Ban95).
       Reproduction toxicity
       The committee did not find data from experimental animal reproduction toxicity
       studies on water-soluble iron compounds.
           In which can be considered being a screening test, no toxicity or
       teratogenicity was observed in developing chick embryos when concentrations
       of ferrous sulphate up to 2.5 mg/egg were injected into the eggs (Ver80).
102-12 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>7      Existing guidelines
       The current administrative occupational exposure limit (MAC) for water-soluble
       iron salts in the Netherlands is 1 mg/m3, 8-hour TWA.
           Existing occupational exposure limits for water-soluble iron salts in some
       European countries and in the USA are summarised in the annex.
8      Assessment of health hazard
       The target organs after exposure by inhalation to water-soluble iron salts are the
       lungs. A human volunteer study has shown that no (instant) effects on lung
       functions were found when healthy as well as asthmatic subjects were exposed to
       a respirable aerosol of ferric sulphate of 0.02 mg Fe/m3 for 2 hours (Kle81). This
       means that the NOAEL would probably be higher than this level.
           A subacute inhalation experiment in rabbits exposed to ferric chloride
       indicated that the LOAEL for effects on the macrophages of the lungs is 1.4 mg
       Fe/m3, as respirable aerosols (Joh92).
           The committee takes the rabbit study with an LOAEL of 1.4 mg Fe/m3 as a
       starting point in deriving a health-based recommended occupational exposure
       limit (HBROEL). For the extrapolation to a HBROEL, an overall assessment
       factor of 12 is established. This factor covers the following aspects: the absence
       of a NOAEL, inter- and intraspecies variation, the relatively short duration of
       exposure, and the type of critical effect. Thus, applying this factor of 12 and the
       preferred value approach, the committee recommends a health-based
       occupational exposure limit of 0.1 mg Fe/m3 for respirable particles of water-
       soluble iron salts.
           The committee underlines that the recommendation is based on a study
       where local effects after exposure to water-soluble ferric salts have been found.
       Therefore, the recommended OEL is not applicable for water-soluble ferrous
       salts.
       The committee considers the toxicological database on water-soluble ferrous
       salts too poor to justify recommendation of a health-based occupational exposure
       limit. The committee concludes that there is insufficient information to comment
       on the level of the present MAC value.
102-13 Iron salts, water-soluble
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<pre>       The committee recommends a health-based occupational exposure limit for
       respirable particles of water-soluble ferric salts of 0.1 mg Fe/m3, as an 8-hour
       time-weighted average (TWA).
       References
ACG96  American Conference of Governmental Industrial Hygienists (ACGIH). Iron salts (soluble). In:
       TLVs and other occupational exposure values - 1996. [CD ROM]. Cincinnati OH, USA: ACGIH®,
       Inc, 1996.
ACG03a American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2003. Cincinnati OH, USA: ACGIH®, Inc, 2003: 73.
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: 36.
Arb02  Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
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102-16 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>               Annex
Occupational exposure limits for water-soluble iron salts in various countries.
country                               occupational           time-weighted           type of          noteb     referencec
- organisation                        exposure limita        average                 exposure limit
                                      ppm       mg/m3
the Netherlands
- Ministry of Social Affairs and      -         1            8h                      administrative             SZW03
Employment
Germany
- AGS                                 -         -                                                               TRG00
- DFG MAK-Kommission                  -         -                                                               DFG03
Great Britain
- HSE                                 -         1            8h                      OES                        HSE02
                                      -         2            15 min
Sweden                                -         -                                                               Swe00
Denmark                               -         1                                                               Arb02
USA
- ACGIH                               -         1            8h                      TLV                        ACG03b
- OSHA                                -         -                                                               ACG03a
- NIOSH                               -         1            10 h                    REL                        ACG03a
European Union
- SCOEL                               -         -                                                               EC03
a
     In all cases as Fe.
b
     S=skin notation; which means that skin absorption may contribute considerably to body burden; sens = substance can cause
     sensitisation.
c
     Reference to the most recent official publication of occupational exposure limits.
102-17         Iron salts, water-soluble
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<pre>102-18 Health-based Reassessment of Administrative Occupational Exposure Limits</pre>

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