<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>Ammonium chloride (fume)
(CAS No: 12125-02-9)
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/093 The Hague, March 30, 2004
</pre>

====================================================================== Einde pagina 1 =================================================================

<br><br>====================================================================== Pagina 2 ======================================================================

<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Ammonium chloride (fume); Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of the
Netherlands, 2004; 2000/15OSH/093.
all rights reserved
</pre>

====================================================================== Einde pagina 2 =================================================================

<br><br>====================================================================== Pagina 3 ======================================================================

<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      ammonium chloride fume 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 February 1998, literature was searched in the databases Medline, Toxline,
      and Chemical Abstracts covering the periods 1966 until February 1998, 1981
      until October 1997, and 1937 until December 1997, respectively, and using the
      following key words: ammonium chloride (and isotopic compounds), NH4Cl,
      and 12125-02-9.
           In December 1998, the President of the Health Council released a draft of the
      document for public review. Comments were received by the following
      individuals and organisations: A Aalto (Ministry of Social Affairs and Health,
      Tampere, Finland) and P Wardenbach, Ph.D. (Bundesanstalt für Arbeitsschutz
      and Arbeitsmedizin, Dortmund, Germany). These comments were taken into
      account in deciding on the final version of the document.
           An additional literature search in Toxline and Medline in September 2003
      did not result in information changing the committee’s conclusions.
2     Identity
      name                           :    ammonium chloride
      synonyms                       :    Amchlor; ammonium muriate; Darammon; Salammoniac; salmiac
      molecular formula              :    NH4Cl
      CAS number                     :    12125-02-9
3     Physical and chemical properties
      molecular weight               :    53.49
      boiling point                  :    520oC (triple point)
      melting point                  :    338oC (sublimation point)
      flash point                    :    not available
      vapour pressure                :    at 160oC: 0.13 Pa
      solubility in water            :    soluble (at 15oC: 26 g/100 mL)
      log Poctanol/water             :    -4.37 (estimated)
      conversion factors             :    not applicable
      Data from Lid96, http://esc.syrres.com.
093-3 Ammonium chloride (fume)
</pre>

====================================================================== Einde pagina 3 =================================================================

<br><br>====================================================================== Pagina 4 ======================================================================

<pre>      Ammonium chloride consists of colourless, odourless crystals or of crystallic
      masses, or it is a white, granular powder. The crystals are somewhat
      hygroscopic. It has a cooling, saline taste (ACG91).
4     Uses
      Ammonium chloride is used in the manufacture of various ammonia compounds
      and dry batteries, as a mordant in dyeing and printing, as a soldering flux,
      fertiliser, and pickling agent in zinc coating and tinning, and in electroplating,
      washing powders, snow treatment, resins and adhesives of urea-formaldehyde,
      medicine, and the food industry. Large amounts of ammonium chloride fume are
      frequently evolved during galvanising operations (ACG91).
          In galvanising plants, the aerosols consist not only of ammonium chloride,
      but also of zinc oxide, zinc chloride and complexes of zinc chlorides, and traces
      of zinc hydroxide (Duf88).
          In Europe, ammonium chloride used to be coded as food additive E510, with
      an unlimited daily intake, but nowadays it is not any longer on the Dutch list of
      permitted food additives as published in the Food and Drugs Act. In the USA,
      ammonium chloride received the GRAS (generally recognised as safe) status in
      1983 (FDA83), and was still listed among these substances in 2003 (see
      21CFR184.1138).
5     Biotransformation and kinetics
      Single oral doses of 1-40 mg/kg bw had no effect on the ammonia (NH3) blood
      level of normal subjects, but caused hyperammonaemia in 32 patients suffering
      from liver cirrhosis (Rud73).
6     Effects and mechanism of action
      Human data
      Until 1977, no cases of intoxication have been reported after occupational
      exposure to ammonium chloride fume (Hou77).
          Two cases of occupational asthma are described due to soft corrosive
      soldering fluxes containing zinc chloride and ammonium chloride. A challenge
      with ammonium chloride caused a fall in FEV1* in one subject but the magnitude
*     FEV1: forced expiratory volume in 1 second.
093-4 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 4 =================================================================

<br><br>====================================================================== Pagina 5 ======================================================================

<pre>      of the response was less than with the whole flux, suggesting that it may not be
      the sole active agent. A challenge with zinc chloride had no effect on this subject.
      In the second case, the authors were unable to challenge with the individual
      constituents of the flux. It is, therefore, not possible to ascribe the effects to a
      particular constituent in the flux (Wei89).
          The oral intake of 12 g ammonium chloride/day (resulting in 0.13-0.21
      g/kg bw/day) for 12 days had no effect on several ventilatory parameters during
      submaximal or maximal exercise of healthy volunteers. Heart rates and
      performance time were similarly unaltered (Bul83).
          Ingestion of ammonium chloride produces metabolic acidosis and diuresis,
      and ammonium chloride is administered for these effects (WHO86)
      Animal data
      Referring to the same source, instillation of 500 mg of ammonium chloride into
      the eyes of rabbits was reported to be mildly (NIO03) or severely irritating
      (Lew92); instillation of 100 mg was listed as severely irritating (NIO03).
          Oral LD50 values of 1650 and 1300 mg/kg bw have been reported for rats and
      mice, respectively (NIO03). Following intraperitoneal or intravenous injections
      into mice, LD50 values were 485 (NIO03) and 367 mg/kg bw (War58),
      respectively. Intravenous injections of doses as low as 78 and 220 mg/kg bw
      were lethal to rabbits and guinea pigs, respectively (NIO03).
      A 2-hour exposure of rabbits to a mist of a 30% solution of ammonium chloride
      caused a slight degree of catarrhic pneumonia and infiltration of small round
      cells in the lungs, a slight degree of vacuolar degeneration in the acinous and
      infiltration of small round cells in Glisson's capsule in the liver, exfoliation of
      epithelium of the uriniferous tubules and infiltration of small round cells in the
      kidney, and a slight degree of atrophy of lymphatic follicles in the spleen
      (Yas59).
          Ex vivo, ammonium chloride increased mucus transport velocity and ciliary
      beat frequency in the tracheobronchial tree isolated from Wistar rats. The
      effective concentrations were in the range of 10-7-10-4 g/mL. The effects were
      more severe in the trachea isolated from rats with bronchitis than from normal
      rats (Mel80).
          The additional amount of ammonia (i.e., above the amount normally
      produced in the body) that can be safely ingested and assimilated is difficult to
      assess. In short-term (28-90 days) studies carried out in rats and pigs, no adverse
      effects were reported at higher levels of ammonia intake (75-545 mg NH3/kg bw/
093-5 Ammonium chloride (fume)
</pre>

====================================================================== Einde pagina 5 =================================================================

<br><br>====================================================================== Pagina 6 ======================================================================

<pre>      day) in the form of sulphamate, phosphate, citrate, or chloride (calculated for
      ammonium chloride this would be 236-1712 mg/kg bw). The effects attributed
      directly to elevated ammonium ion levels are acute pulmonary oedema and
      central nervous system (CNS) toxicity, depression of appetite due to a direct
      effect of the ammonium ion on the brain, and promotion of growth via the use of
      ammonium salts as a source of nitrogen under certain circumstances. Some
      effects (such as renal growth and demineralisation of bone) arising from the
      administration of ammonium chloride seem to be secondary effects of acidosis
      (WHO86).
          The committee found a number of studies concerning the effects of changes
      in urinary parameters on proliferative responses of the bladder epithelium of
      male rats induced by certain compounds. In these experiments, the effect of urine
      acidification by concomitant administration of ammonium chloride was
      investigated, and ‘control’ groups receiving a single dose of ammonium chloride
      only were included.
          De Groot et al. investigated the difference in response to monosodium
      glutamate concerning bladder epithelial hyperplasia in rats with the feeding of
      different basal diets. Groups of male rats (Cpb:WU; Wistar random; n=10/group)
      were fed a cereal-based stock diet or a ‘purified’ diet containing acid casein
      supplemented with methionine as the only protein source, with and without
      monosodium glutamate and with and without acidifying and alkalising
      supplements. One of the groups received ‘purified’ diet containing - the
      acidifying salt - ammonium chloride at concentrations that were gradually
      increased from 1% at week 1 to 5 % at week 6 that was subsequently maintained
      for 7 weeks. [Based on data on mean body weight and food intake presented by
      De Groot et al., the committee estimated that the ammonium chloride levels
      could range from roughly 1500 mg/kg bw/day during week 1 to roughly 3,000
      mg/kg bw/day during week 8-13]. One animal died at week 10, showing
      haemorrhagic fluid in the abdominal cavity, swollen ureters, a blood clot in the
      enlarged urinary bladder, inflammation of the seminal vesicles and prostate, and
      haemothorax. No abnormalities in condition or behaviour were observed in the
      other rats. Body weights of ammonium chloride-treated rats were statistically
      significantly lower at weeks 4, 8, and 12, when compared to controls. Some
      decrease in food intake was noticed in the first 8 weeks. Urinary pH of the
      animals receiving the ammonium chloride-supplemented and the
      unsupplemented ‘purified’ diet ranged from ca. 5.5-5.9 and from ca. 5.6-6.2,
      respectively, during the 13-week treatment period, compared to ca. 6.7-7.7 in
      animals receiving the unsupplemented stock diet. At sacrifice of the surviving
      treated animals, there was a marked, statistically significant increase in relative
093-6 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 6 =================================================================

<br><br>====================================================================== Pagina 7 ======================================================================

<pre>      kidney weights while those of the liver were comparable to controls.
      Microscopic examination included the urinary bladder, ureters, kidneys, liver,
      testes, thyroid with parathyroids, adrenals, and bone. In the ammonium chloride-
      treated rats, only changes in the bladder epithelium were found. Moderate diffuse
      epithelial hyperplasia and severe diffuse hyperplasia with small papillary
      protrusions were seen in 2/10 and 2/10 rats, respectively, while there were focal
      hyperplasia and very small intra-epithelial cysts in 1/10 and 1/10 rats,
      respectively. Although these changes were not seen in any of the control rats, the
      differences in incidence between the 2 groups were not statistically significant.
      The induction of bladder epithelial hyperplasia by dietary ammonium chloride
      was confirmed in a supplementary study of similar design, lasting 15 instead of
      13 weeks, in which 5/9 rats showed moderate diffuse hyperplasia vs. none in 10
      controls (p<0.05; Fisher’s pairwise test). In addition, severe diffuse hyperplasia
      with small papillary protrusions was seen in one ammonium chloride-treated rat
      (Gro88).
          Shibata et al. examined changes of urinary electrolyte levels and pH, and
      DNA synthesis and the morphology of bladder epithelium in groups of F344 rats
      feeding diets containing various carbonates or ammonium chloride with and
      without L-ascorbic acid, for 4 or 8 weeks. One of the groups comprised 11 rats
      receiving 1% ammonium chloride (780 mg/kg bw/day, based on an average body
      weight over this 8 weeks of 200 mg and a food consumption of 15.6 g/rat/day);
      data from Shi89) for 8 weeks. Body weights of ammonium chloride-treated rats
      were statistically significantly decreased at week 4 and 8 when compared to
      untreated control animals. Apart from a decrease in pH (5.9 vs. 6.9 in controls)
      and in potassium levels, urinary parameters (volume; osmolality; ascorbic acid,
      sodium, chloride, calcium, phosphate, and magnesium levels; crystals) were not
      affected. The degree of DNA synthesis, estimated by determining the number of
      cells incorporating bromodeoxyuridine (BrdU) into the DNA per 1000 cells
      (BrdU-labelling index), was comparable among ammonium chloride-treated and
      untreated rats. No morphological changes were observed in bladder epithelium at
      light microscopy and scanning electron microscopy examinations (Shi89).
          In a study to investigate the effects of tributyl phosphate on the urine and
      bladder epithelium in male Sprague-Dawley rats and the effect of urine
      acidification by concomitant administration of ammonium chloride, a ‘control’
      group of 10 rats received daily dietary doses of ammonium chloride of 1.23%
      (roughly 980 mg/kg bw/day based on a mean food intake of 80 g/kg bw/day;
      adapted from Arn97), for 10 weeks. Treatment did not affect body weight
      throughout the study, and no abnormalities were observed during weekly clinical
      evaluations. Urinalyses at the end of the experiment (week 11) showed decreased
093-7 Ammonium chloride (fume)
</pre>

====================================================================== Einde pagina 7 =================================================================

<br><br>====================================================================== Pagina 8 ======================================================================

<pre>      pH (6.04 vs. 7.56 in controls; p<0.05), increased calcium, which is frequently
      seen with acidic urine (11.0 vs. 5.9 mg/dL; p<0.05), and decreased creatinine
      levels (52 vs. 80 mg/dL; p<0.05); there was no crystaluria. Relative and absolute
      bladder and kidney weights of ammonium chloride-treated animals did not differ
      from those of untreated controls. There was no difference in BrdU-labelling
      index between ammonium chloride-treated and untreated control rats.
      Examination by light microscopy did not reveal urothelial changes in the
      bladders of animals of the ammonium chloride group, but focal, small areas of
      superficial cell necrosis, proliferation, and prominent vascularity were seen in
      2/10 animals using scanning electron microscopy. Microscopic examination of
      the kidneys and the stomach did not reveal treatment-related changes. No other
      data were presented (Arn97).
      Carcinogenicity
      Early literature already indicated that ammonium chloride could inhibit tumour
      growth in mice inoculated with the Twort carcinoma, when given via the
      drinking water (Tho43).
      Mutagenicity and genotoxicity
      In vitro, ammonium chloride was negative in a bacterial mutation assay using S.
      typhimurium strains TA92, TA94, TA98, TA100, TA1535, and TA1537 when
      tested with and without rat liver metabolic activation at concentrations up to 10
      mg/plate (Ish84, Ish88).
          Tested in mammalian cell systems, i.e., for polyploidy and chromosomal
      aberrations in Chinese hamster fibroblasts (tested without metabolic activation
      only), ammonium chloride caused an increase in the incidence of cells with
      structural chromosomal aberrations (including gaps), but not of polyploid cells
      (Ish84, Ish88).
      In vivo, ammonium chloride did not induce an increase in the incidence of
      micronucleated polychromatic erythrocytes obtained from the bone marrow of
      male ddY mice, 24 hours after one intraperitoneal injection of doses of 62.5-500
      mg/kg bw or 4 intraperitoneal injections of doses of 31.3-250 mg/kg bw
      (Hay88).
093-8 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 8 =================================================================

<br><br>====================================================================== Pagina 9 ======================================================================

<pre>      Reproduction toxicity
      Khera investigated the possible relationships between maternal acid-base-
      electrolyte imbalance, histological changes in the maternal/extra-embryonic
      tissues, and fetal anomalies induced by maternally toxic doses of ethylene glycol,
      sodium salicylate, and cadmium chloride. As a part of this study, the influence of
      concomitant administration of ammonium chloride on the effects of sodium
      salicylate was examined using a control group of 13 pregnant Sprague-Dawley
      rats given amounts of ammonium chloride of ca. 750 mg/kg bw/day via the
      drinking water on gestational days 7-10*. There was a (not statistically
      significant) increase in the incidence of wavy and supernumerary ribs of 6 and
      2%, respectively, vs. 1 and 1%, respectively, in control animals receiving pure
      drinking water. It is unlikely that these effects can be ascribed to the altered acid-
      base homeostasis in the mother. This was shown in a separate study, where the
      dams were given 421 mg ammonium chloride/kg bw via the drinking water from
      gestational day 7 onwards. After 7 hours, 4 of the 17 parameters measured in
      blood and urine were decreased: PCO2, HCO3- concentration, phosphate
      concentration, and a parameter ‘BE ec F’ (in mEq/l; not explained in the text or
      legenda). After 48 hours, the urinary pH was decreased (p<0.01), but all the other
      parameters were within the normal range (Khe91).
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for ammonium
      chloride (fume) in the Netherlands is 10 mg/m3, 8-hour TWA.
           Existing occupational exposure limits for ammonium chloride (fume) in
      some European countries and in the USA are summarised in the annex.
*     The quantity of ammonium chloride taken up in those 4 days was calculated as follows: 4 (number of days) x 41.7
      mL (mean water consumption/day during these days) x 4.73 mg/mL (concentration of ammonium chloride
      solution administered) = 789 mg. The body weight of the animals on gestational day 11 was estimated to be 265 g
      (body weights at the start of the experiment ranged from 225 - 275 g; the weight gain from gestational days 8-11
      was 15 g - comparable with the control group). Thus, the total intake of ammonium chloride was approximately
      3000 mg/kg bw or 750 mg/kg bw/day.
093-9 Ammonium chloride (fume)
</pre>

====================================================================== Einde pagina 9 =================================================================

<br><br>====================================================================== Pagina 10 ======================================================================

<pre>8      Assessment of health hazard
       Although the critical effect of occupational exposure to ammonium chloride is
       likely to be upper respiratory tract irritation, the committee did not find human
       data from which a concentration-effect relation for inhalation exposure can be
       estimated.
            The committee did not find data from inhalation studies in experimental
       animals.
            Ammonium chloride was mildly or severely irritating to the eyes of rabbits.
       The committee did not find data from studies on skin irritation or sensitisation.
            Oral LD50 values in rats and mice were 1650 and 1300 mg/kg bw,
       respectively.
            Apart from a number of studies concerning the effects of changes in urinary
       parameters on proliferative responses of the bladder epithelium of male rats
       induced by certain compounds, the committee did not find data on the toxicity of
       ammonium chloride following repeated administration. In these experiments, the
       effect of urine acidification by concomitant administration of ammonium
       chloride was investigated, and ‘control’ groups receiving a single high dose of
       ammonium chloride only, for 10-15 weeks, were included. At an estimated
       amount of 780 mg/kg bw for 8 weeks, ammonium chloride caused decreased
       body weights but no morphological changes in bladder epithelium. An estimated
       dose of 980 mg/kg bw, for 10 weeks, did cause hyperplasia in bladder epithelium
       in 2/10 rats, but did not affect body weights or relative and absolute bladder and
       kidney weights. At doses estimated to range from 1500 mg/kg bw at week 1 to
       3000 mg/kg bw from week 6 to week 13 or 15, decreased body weights and
       increased relative kidney weights were observed as well as bladder epithelial
       hyperplasia in approximately half of the animals.
            In a reproduction toxicity study, in which the influence of administration of
       ammonium chloride on the effects of sodium salicylate was investigated in
       Sprague-Dawley rats, administration in the drinking water of doses of
       ammonium chloride of ca. 750 mg/kg bw/day on gestational days 7-10 did not
       cause significant, treatment-related changes in the number of live fetuses per
       litter, the number of resorptions, fetal body weight, or the incidence of fetal
       malformations.
            Ammonium chloride was negative in an in vitro bacterial mutation assay and
       in an in vivo mouse bone marrow micronucleus test (route: intraperitoneal). In an
       in vitro chromosomal aberration assay, it caused an increase in the number of
       human fibroblast cells with structural aberrations (including gaps).
093-10 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 10 =================================================================

<br><br>====================================================================== Pagina 11 ======================================================================

<pre>       The committee considers the toxicological database on ammonium chloride
       (fume) too poor to justify recommendation of a health-based occupational
       exposure limit.
       At exposure to 10 mg/m3 ammonium chloride (fume), the current MAC-value,
       systemic effects are unlikely, but local effects on eyes and respiratory tract may
       occur. Since data on irritation are lacking, the committee concludes that there is
       insufficient information to comment on the level of the present MAC-value.
       References
ACG91  American Conference of Governmental Industrial Hygienists (ACGIH). Ammonium chloride fume.
       In: Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati
       OH, USA: ACGIH®, Inc, 1991: 60.
ACG03a American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2003. Cincinnati OH, USA: ACGIH®, Inc, 2003: 7.
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: 14.
Arb02  Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
       2002: 16 (At-vejledning C.0.1).
Arn97  Arnold LL, Christenson WR, Cano M, et al. Tributyl phosphate effects on urine and bladder
       epithelium in male Sprague-Dawley rats. Fundam Appl Toxicol 1997; 40: 247-55.
Bul83  Bulbulian R, Girandola RN, Wiswell RA. The effect of NH4Cl induced chronic metabolic acidosis on
       work capacity in man. Eur J Appl Physiol 1983; 51: 17-24.
Coh95  Cohen SM, Garland EM, Cano M, et al. Effects of sodium ascorbate, sodium saccharin and
       ammonium chloride on the male rat urinary bladder. Carcinogenesis 1995; 16: 2743-50.
DFG03  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, 2003;
       rep no 39.
Duf88  Dufresne A, Perrault, Roy C, et al. Characterization of ambient air contaminants from hot-dip
       galvanizing plants. Ann Occup Hyg 1988; 32: 179-90.
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.
FDA83  Food and Drug Administration (FDA). Ammonium bicarbonate, ammonium chloride, ammonium
       carbonate, ammonium hydroxide, and mono- and dibasic ammonium phosphate. Proposed
       affirmation of GRAS status as human food ingredients. US FDA. Fed Reg 1978; 43 (65): 14064-8.
093-11 Ammonium chloride (fume)
</pre>

====================================================================== Einde pagina 11 =================================================================

<br><br>====================================================================== Pagina 12 ======================================================================

<pre>Gro88  Groot AP de, Feron VJ, Immel HR. Induction of hyperplasia in the bladder epithelium of rats by a
       dietary excess of acid or base: implications for toxicity/carcinogenicity testing. Food Chem Toxicol
       1988; 26: 425-34.
Hay88  Hayashi M, Kishi M, Sofuni T, et al. Micronucleus tests in mice on 39 food additives and eight
       miscellaneous chemicals. Food Chem Toxicol 1988; 26: 487-500.
Hou77  Houte G van. Verzinken, gevaren en preventie van intoxicaties Belg-Ned Tijdschr Oppervlaktetechn
       Met 1977; 21: 282-5.
HSE02  Health and Safety Executive (HSE). EH40/2002. Occupational Exposure Limits 2002. Sudbury
       (Suffolk), UK: HSE Books, 2002: 12.
Ish84  Ishidate M Jr, Sofuni T, Yoshikawa K, et al. Primary mutagenicity screening of food additives
       currently used in Japan. Food Chem Toxicol 1984; 22: 623-36.
Ish88  Ishidate M Jr, Harnois MC, Sofuni T. A comparative analysis of data on the clastogenicity of 951
       chemical substances tested in mammalian cell cultures. Mutat Res 1988; 195: 151-213.
Khe91  Khera KS. Chemically induced alterations in maternal homeostasis and histology of conceptus: their
       etiologic significance in rat fetal anomalies. Teratology 1991; 44: 259-97.
Lew92  Lewis RJ Sr, ed. Ammonium chloride. In: Sax's dangerous properties of industrial materials. 8th ed.
       New York, USA: Van Nostrand Reinhold, 1992: 223.
Lid96  Lide DR, Frederikse HPR, ed. CRC Handbook of chemistry and physics. 77th ed. Boca Raton FL,
       USA: CRC Press, 1996: 4-38, 6-110.
NIO03  US National Institute for Occupational Safety and Health (NIOSH), ed. Ammonium chloride. In: The
       Registry of Toxic Effects of Chemicals Substances (RTECS) (last update ammonium chloride file:
       December 2000). http://www.cdc.gov/niosh.
Mel80  Melville GN, Ismail S, Sealy C. Tracheobronchial function in health and disease. Respiration 1980;
       40: 329-36.
Rud73  Rudnan D, Smith RB 3rd, Salam AA, et al. Ammonia content of food. Am J Clin Nutr 1973; 26: 487-
       90.
Shi89  Shibata MA, Tamano S, Kurata Y, et al. Participation of urinary sodium, potassium, and L-ascorbic
       acid in the proliferative response of the bladder epithelium after the oral administration of various
       salts and/or ascorbic acid to rats. Food Chem Toxicol 1989; 27: 403-13.
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: 16.
Tho43  Thompson JH, Holt PF, Callow HJ. Inhibition of tumour growth. Nature 1943; 151: 364-5.
TRG00  TRGS 900: Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArbBl
       2000; 2.
War58  Warren KS. The differential toxicity of ammonium salts. J Clin Invest 1958; 37: 497-501.
093-12 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 12 =================================================================

<br><br>====================================================================== Pagina 13 ======================================================================

<pre>Wei89  Weir DC, Robertson AS, Jones S, et al. Occupational asthma due to soft corrosive soldering fluxes
       containing zinc chloride and ammonium chloride. Thorax 1989; 44: 220-3.
WHO86  World Health Organization (WHO): International Programme on Chemical Safety (IPCS).
       Ammonia. Geneva, Switzerland: WHO, 1986; Environmental Health Criteria 54.
Yas59  Yasuhi J. [An experimental study of toxicosis by ammonium chloride]. In Japanese. Igaku Kenkyu
       1959; 29: 4484-503; cited from Chemical Abstracts 58:4957h.
093-13 Ammonium chloride (fume)
</pre>

====================================================================== Einde pagina 13 =================================================================

<br><br>====================================================================== Pagina 14 ======================================================================

<pre>              Annex
Occupational exposure limits for ammonium chloride (fume) in various countries.
country                               occupational                time-weighted      type of exposure  notea      referenceb
- organisation                        exposure limit              average            limit
                                      ppm         mg/m3
the Netherlands
- Ministry of Social Affairs and      -           10              8h                 administrative               SZW03
Employment
Germany
- AGS                                 -           -                                                               TRG00
- DFG MAK-Kommission                  -           -                                                               DFG03
Great-Britain
- HSE                                 -           10              8h                 OES                          HSE02
                                      -           20              15 min             STEL
Sweden                                -           -                                                               Swe00
Denmark                               -           10              8h                                              Arb02
USA
- ACGIH                               -           10              8h                 TLV                          ACG03b
                                      -           20              15 min             STEL
- OSHA                                -           -                                                               ACG03a
- NIOSH                               -           10              10 h               REL                          ACG03a
                                                  20              15 min             STEL
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.
093-14        Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 14 =================================================================

<br><br>