<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>      Perchloromethyl mercaptan
      (CAS reg no: 594-42-3)
      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/037, The Hague, 7 March 2002
037-1
</pre>

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

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

<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Perchloromethyl mercaptan; Health-based Reassessment of
      Administrative Occupational Exposure Limits. The Hague: Health Council of the
      Netherlands, 2002; 2000/15OSH/037.
      all rights reserved
037-2
</pre>

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

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

<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      perchloromethyl mercaptan 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 H Stouten, M.Sc. (TNO Nutrition and
      Food Research, Zeist, the Netherlands).
           The evaluation of the toxicity of perchloromethyl mercaptan has been based
      on the review by the American Conference of Governmental Industrial
      Hygienists (ACG99). Where relevant, the original publications were reviewed
      and evaluated as will be indicated in the text. In addition, literature was retrieved
      from the online data bases Medline, Toxline, Chemical Abstracts, and NIOSHtic
      covering the period 1966 to 26 April 1999 (19990426/UP), 1965 to 29 January 1999
      (19990129/ED), 1967 to 24 April 1999 (19990424/ED; vol 130, iss 18), and 1973 to
      16 July 1998 (19980716/ED), respectively, and using the following key words:
      perchloromethyl mercaptan, trichloromethyl sulfenyl chloride,
      perchloromethanethiol, trichloromethanesulfenyl chloride,
      trichloromethanesulphenyl chloride, trichloromethanethiol, trichloromethyl
      mercaptan, CSCl4, 594-42-3, 75-70-7, and 20434-91-7. HSDB and RTECS, data
      bases available from CD-ROM, were consulted as well (NIO99, NLM99). The final
      literature search has been carried out in April 1999.
           In July 2001, the President of the Health Council released a draft of the
      document for public review. The committee received no comments.
2     Identity
       name                        :   perchloromethyl mercaptan
       synonyms                    :   methane sulfenyl chloride; perchloromethanethiol;
                                       trichloromethylsulfenyl chloride;
                                       trichloromethylsulphenyl chloride;
                                       trichloromethanesulfenyl chloride;
                                       trichloromethanesulphenyl chloride;
                                       thiocarbonyltetrachloride
       molecular formula           :   CCl4S
       structural formula          :   Cl3-C-S-Cl
       CAS reg no                  :   594-42-3
      Data from ACG99, NLM99.
037-3 Perchloromethyl mercaptan
</pre>

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

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

<pre>3     Physical and chemical properties
       molecular weight       :  185.87
       boiling point          :  147-148 oC (decomposes)
       melting point          :  -
       flash point            :  -
       vapour pressure        :  at 20 oC: 0.4 kPa
       solubility in water    :  insoluble
       Log P octanol/water    :  3.47 (estimated)
       conversion factors     :  1 ppm     = 7.7 mg/m 3
       (20 oC, 101.3 kPa)     :  1 mg/m 3 = 0.13 ppm
      Data from ACG99, Env80, NLM99, http://esc.syres.com.
      Perchloromethyl mercaptan is an oily, yellow liquid with a disagreeable, acrid
      odour. It is not flammable. Upon heating or in a fire, it gives off toxic and
      corrosive gases. With water, it reacts in a rate-limiting first step to
      trichlorosulphenic acid (Cl3C-S-OH) and then to thiophosgene-S-oxide
      (Cl2C=S=O). Both steps yield hydrochloric acid (HCl) (ACG99, Env80, NLM99).
            A human odour threshold of 0.0075 mg/m3 (0.001 ppm) has been reported
      (Rut86).
4     Uses
      Perchloromethyl mercaptan is used as an intermediate for the synthesis of dyes
      and fungicides (ACG99).
5     Biotransformation and kinetics
      The commitee did not find experimental data on the absorption, distribution,
      biotransformation, and excretion of perchloromethyl mercaptan.
            However, perchloromethyl mercaptan is thought to be able to react readily
      with nucleophilic groups such as hydroxyl groups (water) or amino and thiol
      groups (peptides, e.g., glutathione). Its metabolism may therefore be similar to
      the fate of the trichloromethylthio moiety of captan
      (1,2,3,6-tetrahydro-N-(trichloromethylthio)-phthalimide) (see Figure 1). Reactions
      with amino or thiol groups yield via a number of steps the very reactive
037-4 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>      thiophosgene. This compound can be detoxified in at least three ways: 1)
      condensation with either free or protein-bound cysteine to, ultimately, TTCA
      (thiazolidine-2-thione-4-carboxylic acid), 2) hydrolysis and/or oxidation to CO2
      and H2S, and 3) reaction with sulphite to a sulphonic acid and its monoxide
      derivative (see metabolism scheme Annex II) (Env80, Hea98).
      Figure 1 Captan.
6     Effects and mechanism of action
      Human data
      Inhalation of unspecified, but low concentrations of perchloromethyl mercaptan
      were stated to have resulted in strong eye, throat, and chest irritation. Exposure
      may induce nausea and vomiting as well (Flu31).
          A few cases of poisoning due to accidental exposure have been reported.
      Due to accidental dermal (face) exposure, a man experienced conjunctival and
      mucosal respiratory tract irritation instantly and, amongst others, extensive
      dispersed toxic bronchopneumonia with global respiratory insufficiency and
      heavy hypoxaemia within 20 hours, upon medical treatment completely healing
      within 14 days (Spá71). In its criteria document, the German DFG presents 3
      cases (reported in an inaugural dissertation) in which dermal and inhalation
      exposure caused, among others, blepharospasms and almost complete corneal
      erosion, pulmonary oedema, coughing, dyspnea, and cyanosis. One of the cases
      was fatal, and tracheal necrosis, (haemorrhagic) oedema of the lungs, brain, and
      heart, marked renal nephrosis, and vacuolization of hepatic centrilobular cells
      were seen at autopsy (Gre98; see also Alt73).
          From a NIOSH health hazard evaluation report, it was cited that at production
      plants with levels below 0.1 ppm (0.8 mg/m3; 8-hour time-weighted average), no
      reports of illness had been filed (ACG99).
037-5 Perchloromethyl mercaptan
</pre>

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

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

<pre>      Animal data
      Irritation
      Perchloromethyl mercaptan was cited to be severely irritating to the skin of
      rabbits (ACG99, NIO99). When amounts of 0.5 to 5 mL/kg of undiluted
      perchloromethyl mercaptan were used to moisten a gauze pad and held in
      contact with the depilated skin of guinea pigs (n=3) for 24 hours, severe skin
      irritation (gross oedema, entire area necrotic surrounded by erythema or
      haemorrhages; eschar; scarring) was observed during the 2-week observation
      period (Eas61). When 0.5 mL of neat test substance was applied to the intact and
      abraded clipped skin of rabbits (n=3/sex/group) under occlusion for 24 hours and
      then washed off, perchloromethyl mercaptan was found to be corrosive yielding
      maximum scores for erythema and oedema at all time points (i.e., at 24 and 72
      hours) (Draize score: 8.0) (Say71).
           Perchloromethyl mercaptan was cited to be severely irritating to the eyes of
      rabbits (ACG99, NIO99). When instilled into the eyes of rabbits, perchloromethyl
      mercaptan was highly corrosive causing complete destruction of the eyes. Three
      out of the 6 animals died 7 to 10 days after treatment (Say71).
      Single exposure
      An LC50 of ca. 13 ppm (ca. 100 mg/m3) has been estimated when groups of rats
      (n=5/sex/group) were exposed to concentrations of 9 to 2314 ppm (69-17,818
      mg/m3), for 1 hour (observation time: 14 days). At all levels tested, eye and
      mucosal irritation as well as dyspnoea, gasping, and acute depression were seen.
      All animals survived exposure to 9 ppm (69 mg/m3). At autopsy of the animals
      that died due to exposure to higher levels, pulmonary oedema, congestion of
      heart and liver, and inflammation of the pericardial and peritoneal membranes and
      of the upper gastrointestinal tract were observed. There was inflammation of
      mouth and nasal mucosa in all cases. At levels of 122 ppm (940 mg/m3) and
      higher, animals showed total corneal opacity (Say71). In a separate paper, 1-hour
      LC50s of 11 and 16 ppm (85 and 123 mg/m3) were reported in male and female rats,
      respectively (Ver77). All rats (number not reported) died due to a 4-hour
      exposure to 34 ppm (262 mg/m3) (Izm82). All 4 rats died following a 1-hour
      exposure to 100 ppm (770 mg/m3) and 3/4 following a 6-hour exposure to 10 ppm
      (77 mg/m3). Animals showed lethargy and respiratory difficulties and lung
      oedema upon autopsy (Gag70). For mice, a 2-hour LC50 of 38 ppm (293 mg/m3)
037-6 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>      has been listed (Izm82), while in another paper, a 3-hour LC50 of 9 ppm (69 mg/m3)
      was cited (Alt73). Both mice and cats (numbers not indicated) died from lung
      oedema within 1 to 2 days following a 15-minute exposure to 45 ppm (347 mg/m3)
      (Flu31).
           In rabbits, dermal LD 50s of 1410 and 1780 mg/kg bw have been reported
      (Say71, Ver77). No signs of toxicity or mortality were observed in animals (n=4)
      treated under occlusion with 464 or 1000 mg/kg bw. Slight depresssion was seen
      after treatment with 2150 mg/kg bw, and 3/4 rabbits died within 3 to 7 days. Upon
      autopsy, these latter animals showed severe haemorrhages of the
      gastrointestinal tract and moderate haemorrhages of the lungs (Say71). In a skin
      irritation study, guinea pigs died within 2 days after application of doses of 2.5
      mL/kg bw (i.e., ca. 4250 mg/kg) and higher (Eas61).
           An oral LD 50 in rats of 83 mg/kg bw has been cited (ACG99, NIO99).
      Following administration of single oral doses of 215-2150 mg/kg bw to male rats
      (Sprague-Dawley; n=5/group), the LD 50 was calculated to be 909 mg/kg bw. No
      mortality, signs of toxicity, or gross pathology were seen at 215 and 464 mg/kg
      bw while doses of 1000 and 2150 mg/kg resulted in severe depression, diarrhea,
      excessive urination and mortality (in 4/5 of each group). In the animals that died,
      slight and severe haemorrhages were noted in lungs and adrenal glands and in
      liver and kidneys, respectively (Say71). Given oral doses of 50-800 mg/kg to rats
      (undiluted and 10% solution) and mice (10 and 1% solution), the LD 50 was
      between 400-800 mg/kg bw in both species. Symptoms included weakness,
      darkening of the eyes, cyanosis, laboured respiration, diarrhea, tremors,
      prostration, and signs of irritation. In rats given a single oral dose of 200 mg/kg
      bw, no methaemoglobin was found (Eas61).
           An iv LD 50 in mice of 56 mg/kg bw has been reported (Gre98). Following
      single ip injections, LD 50s in rats and mice were 25 and 10-25 mg/kg bw,
      respectively (Eas61).
      Repeated exposure
      In a poorly documented paper (summarising single and repeated exposure
      studies of over 100 chemicals), 20 6-hour exposures to 2 ppm (15 mg/m3) were
      stated to have induced initial respiratory difficulties and congested lungs in male
      rats (n=4) while no toxic signs and organ pathology were seen following 20
      6-hour exposures to 0.5 ppm (4 mg/m3) (n=4, both males and females tested)
      (Gag70).
037-7 Perchloromethyl mercaptan
</pre>

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

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

<pre>          No treatment-related mortality was observed in rats (Sprague-Dawley;
      n=15/sex/group) exposed to 0 and ca. 0.02, 0.1, and 1.1 ppm (0.13, 1.0, 8.7 mg/m3),
      6 hours/day, 5 days/week, for 2 weeks. At the highest dose level, clinical signs
      including haircoat stains, laboured breathing, tremors, and decreased body
      weight gain were seen. Necropsy observations were restricted to the lungs
      showing oedema, increased weights, and increased mucus secretion. Upon
      microscopic examination, only effects on the respiratory tract (alveolitis,
      interstitial hyperplasia, perivascular oedema, mild nasal epithelial changes) were
      seen. In the mid-concentration group, only mild nasal epithelial changes were
      reported while there were no effects in the animals exposed to 0.02 ppm (study
      reported in an abstract only) (Kna87b).
          When rats (Sprague-Dawley CD; n=18/sex/group) were exposed to 0 and ca.
      0.01, 0.08, and 0.6 ppm (0.11, 0.6, 4.4 mg/m3), 6 hours/day, 5 days/week, for 14
      weeks (70-72 exposures), survival rates were not affected. Statistically significant
      body weight (gain) decreases were found in the animals of the
      high-concentration group only: in females, throughout the study; in males, at
      weeks 2 and 3. There were no effects on food consumption. Apart from a slight
      increase in the incidence of salivation in the male animals of the
      high-concentration group and of sneezing in the female animals of the
      mid-concentration group and in the male and female animals of the
      high-concentration group, in-life observations did not show consistent
      treatment-related clinical signs of toxicity. Except for a decrease in median urine
      specific gravity in high-concentration females at study termination, no
      treatment-related, biologically significant effects were found upon interim and
      termination clinical chemistry analyses (haematology, blood chemistry,
      urinalysis). Treatment caused an increase in the absolute (males only) and
      relative total lung weights (both males and females) in the high-concentration
      group, increases in accessory lobe dry weights in the male animals of the low-
      and high-concentration group, and decreases in the wet:dry weight ratios of the
      accessory lobes in the male and female animals of these latter exposure groups.
      Furthermore, there were changes in the relative kidney (increases) and absolute
      brain (decreases) weights in all female exposure groups, but these changes did
      not show a dose-response relationship. In addition, relative heart weights were
      increased in the female animals of the low- and high-concentration groups. At
      necropsy, the only treatment-related gross finding was the finding of mucus
      within the tracheas of 2 female and 4 male animals of the high-concentration
      group. Microscopic changes were limited to the respiratory tract, especially the
      nasal cavities of the animals exposed to 0.6 ppm (4.4 mg/m3). These included
037-8 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>      residues of purulent exudates in 16/18 males and 12/18 females, acute or
      subacute respiratory epithelial inflammation in 13/18 males (mostly of slight
      severity) and 8/18 females (mostly of minimal severity), acute inflammation of
      stratified squamous nasal epithelium (“minimal” and “slight”) in 3/18 males, and
      respiratory epithelial hypertrophy and/or hyperplasia in 7/18 males (all of slight
      severity) and 2/18 females (“slight” and “moderate” or more), and respiratory
      epithelial squamous metaplasia in 2/18 males (“slight” and “moderate” or more).
      In some of the animals (5 males, 1 female), there was mostly minimal interstitial
      pneumonia. At 0.08 ppm (0.6 mg/m3), one female animal showed purulent exudate,
      stratified squamous nasal epithelial inflammation, and squamous respiratory
      epithelial metaplasia, and one male animal purulent exudate. In the animals
      exposed to 0.01 ppm (0.11 mg/m3), no microscopic changes were seen. Apart from
      one isolated tumour, i.e., a mammary gland adenocarcinoma in a female animal of
      the mid-concentration, no neoplastic lesions were observed (Kna87a).
           The committee feels it difficult to assess the significance of the changes in
      brain, kidney, and heart weights in the exposed females. In view of the lack of a
      clear dose-response, the absence of these effects in the male animals, and the
      feeling that this reactive compound will induce local effects before systemic
      effects, the committee considers these changes as probably not treatment
      related. Based on the histological effects on the respiratory tract epithelium
      found in 2/36 animals exposed to 0.08 ppm (0.6 mg/m3), the committee places the
      NOAEL in this study at 0.01 ppm (0.11 mg/m3).
           When rats (n=7), guinea pigs (n=7), and dogs (n=2) were exposed to 1 ppm
      (7.7 mg/m3) perchloromethyl mercaptan, 8 hours/day, 5 days/week, for 3 months,
      6/7 guinea pigs died within 3 weeks while all other animals survived. In-life and
      postmortem macro- and microscopic observation showed irritation (conjunctiva
      of the eyes, respiratory tract mucous membranes) to be the principle effect. This
      irritation caused secondary infections in, especially, guinea pigs (pneumonia)
      and dogs (bronchiolitis, foci of bronchopneumonia) (Hor52).
      Mutagenicity and genotoxicity
      In vitro, in bacteria, perchloromethyl mercaptan was mutagenic in S.
      typhimurium strains TA1535, TA1537, TA1538, TA98, TA100 (both with and
      without metabolic activation) (Maj82a) as well as in DNA-polymerase-deficient
      E. coli (pol A 1- assay) (tested without metabolic activation only (Ros80). In
037-9 Perchloromethyl mercaptan
</pre>

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

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

<pre>       mammalian cells, there were positive results in the mouse lymphoma L5178Y
       TK+/- forward mutation assay both with and without induced rat-liver metabolic
       activation (Maj83a). Testing in Chinese hamster ovary cells both with and
       without metabolic activation at sufficiently high doses did not induce significant
       increases in the incidences of chromosomal aberrations and SCEs. However, the
       occurrence of elevated aberration frequencies and complex chromosome
       rearrangement figures were concluded to indicate a weak potential clastogenic
       activity (Maj83b). Perchloromethyl mercaptan inhibited concentration
       dependently the DNA polymerase activity in isolated bovine liver nuclei (Dil80).
       In the morphological transformation assay in BALB/3T3 cells, a statistically
       significant increase (almost a doubling of control values) in the numbers of
       transformed foci was found at a single dose of 0.0075 µL/mL. The next two higher
       concentrations did not induce significant responses but decreases in cell
       survival (from ca. 90 % to < 60%) may have masked a weak positive response
       (Maj82b).
           In vivo, no significant increases in micronuclei were found in the bone
       marrow of mice (CDl; n=5/sex/group) exposed by inhalation to 1.6 and 4.2 ppm
       (12, 32 mg/m3), for 6 hours, and sacrificed after 24, 48, or 72 hours.
       Concentrations were selected from a preceding range finding in which 6-hour
       exposures to 2.7 and 5.7 ppm (21, 44 mg/m3) were said to cause reduced activity
       and mortality (no details presented). No reduction in PCE frequency was seen in
       the bone marrow of these animals when harvested 72 hours after ending
       exposure. The authors did not present data on possible toxic effects observed
       during the micronucleus test; due to the great variation and the lack of
       consistency in the PCE frequency determined at the various time points, the
       bone marrow toxicity could not be assessed (Maj84).
       The committee did not find data on the potential carcinogenicity or reproduction
       toxicity of perchloromethyl mercaptan.
7      Existing guidelines
       The current administrative occupational exposure limit (MAC) for
       perchloromethyl mercaptan in the Netherlands is 0.8 mg/m3 (0.1 ppm), 8-hour
       TWA.
           Existing occupational exposure limits for perchloromethyl mercaptan in some
       European countries and in the USA are summarised in Annex I.
037-10 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>8      Assessment of health hazard
       Although no data were found on the kinetics of perchloromethyl mercaptan per
       se, the compound is thought to be metabolised to the very reactive
       thiophosgene which can readily be detoxified by condensation with free or
       protein-bound cysteine, hydrolysis and/or oxidation, or reaction with sulphite.
            Perchloromethyl mercaptan is corrosive to the eyes and the skin of
       experimental animals. From 1-hour LC50 values in rats of 85-123 mg/m3 (11-16
       ppm), the committee concludes that perchloromethyl mercaptan is very toxic by
       inhalation. From dermal and oral LD 50 values of 1410 and 1780 (both in rabbits)
       and ca. 400-900 (rats) mg/kg bw, respectively, the committee concludes that the
       compound is harmful in contact with skin and if swallowed.
            Data from acute and repeated inhalation studies showed that irritation of the
       eyes and the respiratory tract is the critical effect. In a well-performed 14-week
       study using rats (Kna87a), exposure to 4.4 mg/m3 (0.6 ppm) caused increased
       lung weights and histological changes in the noses of the majority of the
       animals. After exposure to 0.6 mg/m3 (0.08 ppm), one out of 18 female animals
       showed, stratified squamous nasal epithelial inflammation, and squamous
       respiratory epithelial metaplasia and 1/18 male animals purulent exudate. No
       effects were observed at 0.11 mg/m3 (0.01 ppm).
            In in vitro mutagenicity/genotoxicity testing, perchloromethyl mercaptan was
       mutagenic in bacteria and in a mammalian cell system. It showed weak responses
       in a clastogenicity and a transformation assay. In vivo, it did not induce
       micronuclei in the bone marrow of mice after a single 6-hour exposure up to 32
       mg/m3 (4.2 ppm), but bone marrow toxicity was not clearly assessed.
            The committee did not find data on the potential carcinogenicity or
       reproduction toxicity.
            The in vitro mutagenicity of perchloromethyl mercaptan is reason for
       concern, and the compound may, therefore, be considered as a suspect
       carcinogen. On the other hand, a negative result was obtained in an in vivo bone
       marrow micronucleus assay in mice, although it is not clear whether or not the
       test substance had reached the bone marrow. The committee considers
       perchloromethyl mercaptan to be a very reactive compound which will be
       detoxified rapidly and will not pose a carcinogenic risk at concentrations low
       enough to prevent effects on the respiratory tract as described above. This is
       supported by the data on captan, a pesticide rapidly decomposing into, amongst
       others, perchloromethyl mercaptan, as evaluated by the Dutch Expert Committee
037-11 Perchloromethyl mercaptan
</pre>

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

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

<pre>       on Occupational Standards (DECOS) (Hea98). Following oral administration (the
       only route tested), captan was carcinogenic in mice, but not in rats, inducing
       intestinal tumours at high oral doses. DECOS concluded that captan was
       genotoxic/mutagenic in vitro, but not in vivo, based on the majority of negative
       results in in vivo tests, especially those of the DNA binding test and of the
       nuclear aberration test both performed in the target organ (i.e., the murine small
       intestine), and that the tumour formation in the mouse was due to overwhelming
       of detoxification mechanisms. DECOS took a LOAEL of 0.13 mg/m3 from a
       13-week inhalation study, in which minimal to mild hyperplasia of laryngeal
       squamous epithelium was found, as a starting point for standard setting for
       captan.
           Therefore, the committee is of the opinion that the NOAEL of 0.11 mg/m3
       (0.01 ppm) from the 14-week inhalation rat study (Kna87b) can be taken 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 8 is established. This factor covers the following aspects: intra- and
       interspecies variation, differences between experimental conditions and the
       exposure pattern of the worker, and the type of critical effect. Thus, applying this
       factor of 8 and the preferred value approach, a health-based occupational
       exposure limit of 0.01 mg/m3 is recommended for perchloromethyl mercaptan.
       The committee recommends a health-based occupational exposure limit for
       perchloromethyl mercaptan of 0.01 mg/m3, as an 8-hour time-weighted average
       (TWA).
       References
ACG99  American Conference of Governmental Industrial Hygienists (ACGIH). Perchloromethyl
       mercaptan. In: TLVs ® and other occupational exposure values - 1999. [CD-ROM].
       Cincinnati OH, USA; ACGIH® , Inc, 1999.
ACG00  American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2000. Cincinnati OH, USA: ACGIH® , Inc, 2000: 96.
ACG01  American Conference of Governmental Industrial Hygienists (ACGIH). 2001 TLVs ® and
       BEIs® . Threshold Limit Values for chemical substances and physical agents. Biological
       Exposure Indices. Cincinnati OH, USA: ACGIH® , Inc, 2001: 46.
Alt73  Althoff H. Tödliche Perchlormethylmercaptan-Intoxikation. Arch Toxicol 1973; 31:
       121-135.
037-12 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>Arb00a Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark:
       Arbejdstilsynet, 2000; (At-vejledning C.0.1).
Arb00b Arbetarskyddstyrelsen. Hygieniska gränsvärden och åtgärder mot luftföroreningar. Solna,
       Sweden: National Board of Occupational Safety and Health, 2000; (Ordinance AFS 2000/3).
CEC00  Commission of the European Communities (CEC). Commission Directive 2000/39/EC of 8
       June 2000 establishing a first list of indicative occupational exposure limit values in
       implementation of Council Directive 98/24/EC on the protection of the health and safety of
       workers from the risks related to chemical agents at work. Official Journal of the European
       Communities 2000; L142 (16/06/2000): 47-50.
DFG01  Deutsche Forschungsgemeinschaft (DFG): Commission for the Investigation of Health
       Hazards of Chemical Compounds in the Work Area. List of MAK and BAT values 2001.
       Maximum concentrations and biological tolerance values at the workplace. Weinheim, FRG:
       Wiley-VCH, 2001: 88; (rep no 37).
Dil80  Dillwith JW, Lewis RA. Inhibition of DNA polymerase activity in isolated bovine liver nuclei
       by captan and related compounds. Pestic Biochem Physiol 1980; 14: 208-16.
Eas61  Eastman Kodak Company. Toxicity and health summary and toxicity report on
       trichloromethanesulfenyl chloride. Rochester NY, USA: Eastman Kodak Company, Health,
       Safety, and Human Factors Lab, 1961 (available from NTIS, Springfield VA, USA; order no
       NTIS/OTS0533569).
Env80  Enviro Control, Inc. Hazard information review. Trichloromethanesulfenyl chloride.
       Rockville MD, USA: Enviro Control, Inc, 1980.
Flu31  Flury F, Zernicke F. Schädliche Gase, Dämpfe, Nebel, Rauch- und Staubarten. Berlin, FRG:
       Julius Springer, 1931: 362.
Gag70  Cage JC. The subacute inhalation toxicity of 109 industrial chemicals. Br J Ind Med 1970;
       27: 1-18.
Gre98  Greim H, ed. Perchlormethylmercaptan. In: Gesundheidsschädliche Arbeitsstoffe.
       Toxikologisch-arbeitsmedizinische Begründungen von MAK-Werte (Maximale
       Arbeitsplatz-Konzentrationen). (1st-27th ed). Weinheim, FRG: VCH Verlagsgesellschaft
       mbH, 1998.
Hea98  Health Council of the Netherlands: Dutch Expert Committee on Occupational Standards.
       Captan. Health-based recommended occupational exposure limit. The Hague, the
       Netherlands: Health Council of the Netherlands, 1998; draft report.
Hor52  Horn HJ. Perchloromethyl mercaptan (PCMM). Chronic inhalation toxicity. Falls Church
       VA, USA: Hazleton Laboratories, 1952 (available from NTIS, Springfield VA, USA; order no
       NTIS/OTS0538474).
HSE01  Health and Safety Executive (HSE). EH40/2001. Occupational Exposure Limits 2001.
       Sudbury (Suffolk), England: HSE Books, 2001.
037-13 Perchloromethyl mercaptan
</pre>

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

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

<pre>Izm82  Izmerov NF, Sanotsky IV, Siderov KK. In: Toxicometric parameters of industrial toxic
       chemicals under single exposure. Moscow, Russia: Centre of International Projects, 1982: 97.
Kna87a Knapp HF, Thomassen RW. Subchronic inhalation study with perchloromethyl mercaptan
       (PMM) in rats. Farmington CT, USA: Stauffer Chemical Company, 1987; (final rep, rep no
       T-11848) (available from NTIS, Springfield VA, USA; order no NTIS/OTS0545675).
Kna87b Knapp HF, MacAskill SM, Zwicker GM, et al. Effects in rats of repeated inhalation exposure
       to perchloromethyl mercaptan. Toxicologist 1987; 7: 191.
Maj82a Majeska JB. Perchloromethyl mercaptan (PMM) (Batch No 241). Mutagenicity evaluation
       in Salmonella typhimurium. Farmington CT, USA: Stauffer Chemical Company,
       Environmental Health Center, 1982; (rep no T-10842) (available from NTIS, Springfield
       VA, USA; order no NTIS/OTS0558749).
Maj82b Majeska JB. Perchloromethyl mercaptan (PMM) (Batch No 241). Morphological
       transformation in BALB/3T3 cells. Farmington CT, USA: Stauffer Chemical Company,
       Environmental Health Center, 1982; (rep no T-10844) (available from NTIS, Springfield
       VA, USA; order no NTIS/OTS0558749).
Maj83a Majeska JB. Perchloromethyl mercaptan (PMM) (Batch No 241). Mutagenicity evaluation
       in mouse lymphoma multiple endpoint test, forward mutation assay. Farmington CT, USA:
       Stauffer Chemical Company, Environmental Health Center, 1983; (rep no T-10843)
       (available from NTIS, Springfield VA, USA; order no NTIS/OTS0558749).
Maj83b Majeska JB. Perchloromethyl mercaptan (PMM) (Batch No 241). Mutagenicity evaluation
       in Chinese hamster ovary cytogenetic assay. Farmington CT, USA: Stauffer Chemical
       Company, Environmental Health Center, 1983; (rep no T-11711) (available from NTIS,
       Springfield VA, USA; order no NTIS/OTS0558749).
Maj84  Majeska JB. Perchloromethyl mercaptan (PMM) (Batch No 241). Mutagenicity evaluation
       in bone marrow micronucleus. Farmington CT, USA: Stauffer Chemical Company,
       Environmental Health Center, 1984; (rep no T-11857) (available from NTIS, Springfield
       VA, USA; order no NTIS/OTS0558749).
NIO99  National Institute for Occupational Safety and Health (NIOSH). Methanesulfenyl chloride,
       trichloro-. In: Registry of Toxic Effects of Chemical Substances (RTECS) [CD-ROM], issue
       July 1999. SilverPlatter International, 1999 (last update perchloromethyl mercaptan file:
       July 1999).
NLM99  US National Library of Medicine (NLM). Trichloromethanesulfenyl chloride. In: Hazardous
       Substances Data Bank (HSDB). [CD-ROM], issue July 1999. SilverPlatter International, 1999
       (last update perchloromethyl mercaptan file: January 1999).
Ros80  Rosenkranz HS, Leifer Z. Determining the DNA-modifying activity of chemicals using
       DNA-polymerase-deficient Escherichia coli. Chem Mutagens 1980; 6:109-47.
037-14 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

<br><br>====================================================================== Pagina 15 ======================================================================

<pre>Rut86  Ruth JH. Odor thresholds and irritation levels of several chemical substances: a review. Am
       Ind Hyg Assoc J 1986; 47: A-142-A-151.
Say71  Saylor JF, Bullock CH. Perchloromethyl mercaptan. Stauffer Chemical Company, Western
       Research Center, 1971; (Toxicol Lab rep T-1638) (available from NTIS, Springfield VA,
       USA; order no NTIS/OTS0545331).
Spá71  Spáilová M. Akutní inhalaní poškození perchlórmethylmerkaptanem. Prac Lek 1971; 23:
       278-9 (in Czech with English summary).
SZW01  Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2001. The
       Hague, The Netherlands: Sdu, Servicecentrum Uitgevers, 2001: 37.
TRG00  TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe.
       BArbBl 2000; 2
Ver77  Vernot EH, MacEwen JD, Haun CC, et al. Acute toxicity and skin corrosion data for some
       organic and inorganic compounds and aqueous solutions. Toxicol Appl Pharmacol 1977; 42:
       417-23.
037-15 Perchloromethyl mercaptan
</pre>

====================================================================== Einde pagina 15 =================================================================

<br><br>====================================================================== Pagina 16 ======================================================================

<pre>            Annex I
Occupational exposure limits for perchloromethyl mercaptan in various countries.
country organisation                occupational             time -weighted   type of          notea    lit refb
                                    exposure limit           average          exposure limit
                                    ppm        mg/m 3
The Netherlands
- Ministry of Social Affairs and    0.1        0.8           8h               administrative            SZW01
Employment
Germany
- AGS                               -          0.8           8h                                         TRG00
- DFG MAK-Kommission                -c         -                                                        DFG01
Great Britain
- HSE                               -          -                                                        HSE01
Sweden                              -          -                                                        Arb00b
Denmark                             0.1        -             8h                                         Arb00a
USA
- ACGIH                             0.1        0.76          8h               TLV                       ACG01
- OSHA                              0.1        0.8           8h               PEL                       ACG00
- NIOSH                             0.1        0.8           10 h             REL                       ACG00
European Union
- SCOEL                             -          -                                                        CEC00
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
     Listed among substances for which studies of the effects in man or experimental animals have yielded
     insufficient information for the establishment of MAK values
037-16      Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 16 =================================================================

<br><br>====================================================================== Pagina 17 ======================================================================

<pre>           Annex II
Figure2 Biotransformation scheme of perchloromethyl mercaptan (adapted from Env80 and Hea98).
037-17     Perchloromethyl mercaptan
</pre>

====================================================================== Einde pagina 17 =================================================================

<br><br>