<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>Methyl ethyl ketone peroxide
(CAS No: 1338-23-4)
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/050, The Hague, 31 October 2002
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<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Methyl ethyl ketone peroxide; Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of
the Netherlands, 2002; 2000/15OSH/050.
all rights reserved
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of methyl
      ethyl ketone peroxide 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 of the
      Academic Medical Centre, Amsterdam, the Netherlands).
           Literature was retrieved from the databases Medline, Embase, Current
      Contents, and Chemical Abstracts, starting from 1966, 1988, 1970, and 1970,
      respectively, and using the following key words: methyl ethyl ketone peroxide,
      butanone peroxide, MEKP, and 1338-23-4. HSEline, Cisdoc, Mhidas,
      NIOSHTIC (covering the period 1985/87 until 1997), and Poltox (Toxline,
      Cambridge Sc Abstr, FSTA) (covering information until 1994), databases
      available from CD-ROM, were consulted as well. Data considered to be critical
      were evaluated by reviewing the original publications. The final literature
      search was carried out in January 1998, followed by an additional search in
      June 2001.
           In September 2001, the President of the Health Council released a draft of
      the document for public review. The committee received no comments.
2     Identity
       name                     :     methyl ethyl ketone peroxide
       synonyms                 :     2-butanone peroxide
       molecular formular       :     C8H16O4
       structural formula       :
       CAS number               :     1338-23-4
050-3 Methyl ethyl ketone peroxide
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<pre>3     Physical and chemical properties
       molecular weight           :      176.2
       boiling point              :      80oC
       melting point              :      not known
       flash point                :      52-93oC
       vapour pressure            :      not known
       solubility in water        :      not soluble
       log Poctanol/water         :      not known
       conversion factors         :      1 mg/m3 = 0.14 ppm
       (200C, 101.3 kPa)                 1 ppm = 7.3 mg/m3
      Data from ACG99, Zei93.
      Methyl ethyl ketone peroxide (MEKP) is a colourless liquid. The pure chemical
      is an unstable peroxide capable of releasing molecular oxygen. It is shock,
      sunlight, and heat sensitive, and undergoes explosive decomposition at 110oC. It
      can also undergo spontaneous ignition or decomposition if mixed with readily
      oxidisable organic or flammable materials or chemical reactants. Because of this
      high reactivity, it is sold commercially as a colourless liquid mixture of
      approximately 60% MEKP and 40% diluent that may be any combination of
      dimethyl phthalate, cyclohexanone peroxide, or diallyl phthalate (ACG99,
      Zei93).
            The odour threshold is not known.
4     Uses
      MEKP is a commonly used curing agent for thermosetting polyester resins, a
      cross-linking agent and catalyst used in the production of other polymers and
      polyester resins. It is used in the automobile, airline, boating, fabric, and paint
      industries (Fra90, Pur79). In biochemistry, MEKP is used for inducing
      experimental lipid peroxidation in animals.
5     Biotransformation and kinetics
      There is very little data available on the kinetics of MEKP.
050-4 Health-based Recommended Occupational Exposure Limits
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<pre>          In a review on toxic effects in humans, Zeiger stated that in the working
      environment, exposure occurs by inhalation of aerosolised MEKP during the
      spraying procedure used in some of the manufacturing processes, or by dermal
      exposure to the aerosol or liquid substance (Zei93).
6     Effects and mechanism of action
      Human data
      A few cases of work-related allergic contact dermatitis have been reported with
      positive reactions to MEKP upon patch testing in the patients involved (Bhu97,
      Bou63, Mal57, Ste92).
          Fraunfelder et al. studied ocular injury from accidental direct contact with
      MEKP vapour or solvent (full strength or diluted) in 13 male patients, ranging
      in age from 22 to 68 years. There were 4 clinical ocular patterns: mild injury,
      moderate injury, severe injury, and delayed keratitis. Corneoscleral limbus and
      cornea were the primary areas of chronic irritation secondary to exposure to
      MEKP, but marked hyperaemia of bulbar and palpebral conjunctiva occurred
      with exacerbations. Significant photophobia and epiphora were common. Tear
      film break-up times were usually abnormal. Markedly decreased or absent
      conjunctival and corneal sensitivity were common, and these were permanent in
      cases of severe injury. The delayed MEKP keratitis was characterised by its
      slow progression, exacerbations and remissions, corneal hypoaesthesia, and
      similar corneal changes. Resembling delayed mustard gas keratitis, the effects
      of MEKP may be the result of its alteration of corneal macromolecules to
      produce new antigens resulting in an autoimmune response directed at the
      cornea leading to the delayed keratitis observed. Generally, a major factor in the
      severity of ocular effects was the length of time from exposure to MEKP to
      adequate lavage (Fra90).
          McGlothlin and Thoburn performed a health survey on workers exposed to
      various ketones and acrylic resins during the manufacture of fibrous
      glass-reinforced plastic tubs and showers. Environmental sampling of a variety
      of chemicals, among which toluene diisocyanate, showed that none of the
      chemicals tested exceeded the recommended OSHA standards. MEKP was the
      primary contaminant that the workers were exposed to with levels ranging from
      0.19 to 1.24 mg/m3 (0.026 to 0.17 ppm). Pulmonary function tests performed
      before and after shifts on 30 workers were usually normal, but 5 workers
      showed significant decreases in the functions over the shift. Predominant
050-5 Methyl ethyl ketone peroxide
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<pre>      symptoms were nose and throat irritation, headaches, dizziness, and breathing
      problems. One worker had a hyperreactivity to toluene diisocyanate (McG81).
           The toxic oral dose of MEPK (in dimethyl phthalate) has been reported to
      be 50 to 100 mL. Case reports showed that ingestion of MEKP resulted in acute
      toxic symptoms such as gastrointestinal bleeding, abdominal burns, necrosis,
      stomach perforation, oesophageal stricture, severe metabolic acidosis, rapid
      hepatic failure, rhabdomyolysis, and respiratory failure while temporary cardiac
      arrest and toxic myocarditis were observed as well. Upon autopsy of one case,
      massive periportal hepatic necrosis accompanied by atypical pseudoductular
      proliferation were seen (Zei93).
      Animal data
      Instillation of strong solutions of MEKP (in dimethyl phthalate) into the eyes of
      rabbits caused extensive effects on the cornea, iris, and conjunctiva while
      weaker solutions affected the conjunctiva only. Treatment with 3% solutions
      resulted in Draize scores of 57 at Day 1 and 2 following treatment, decreasing
      to 11 and 7 at day 3 and 7, respectively.* The maximal concentration not
      irritating to the eyes of rabbits was reported to be 0.6% peroxide (in dimethyl
      phthalate). No irritation occurred when eyes were washed within 4 seconds after
      instillation (Flo58).
           The maximal concentration not irritating to the shaved skin of rabbits was
      found to be 1.5% peroxide. Single application of undiluted material caused no
      immediate discomfort but there was a severe delayed reaction consisting of
      erythema, oedema, and vesiculation within 2 or 3 days (Flo58).
      Four-hour inhalation LC50 values of 1460 and 1240 mg/m3 (200 and 170 ppm)
      were found for rats and mice, respectively. Hyperaemia of the lungs, with
      petechial haemorrhages on the lung surfaces in some animals and gross
      haemorrhages in others, as well as occasional nasal porphyrin exudate were
      seen. The intraperitoneal and oral LD50 values in rats were 65 and 484 mg/kg
      bw, respectively (Flo58).
      The committee did not find adequate data on toxic effects following repeated
      exposure by inhalation to MEKP. Floyd and Stokinger reported that no
      significant amount of methaemoglobin was found in rats exposed by inhalation
*     The maximum Draize score for effects on cornea, iris, and conjunctivae is 110. Scores of 57 and of 11 and 7 are
      indicative of severe and minimal irritation, respectively.
050-6 Health-based Recommended Occupational Exposure Limits
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<pre>      to low (not further specified) levels of MEKP for 3 days or in rats given
      intraperitoneal injections (doses not presented), 3 times/week, for 5 weeks.
      When MEKP was given orally or intraperitoneally to rats at 1/5 LD50 (i.e., 97
      and 13 mg/kg bw, respectively), 3 times/week, for 7 weeks, 5/5 and 2/5 animals
      died during the study. Body weights were clearly affected in the orally but not
      in the intraperitoneally treated animals. Rough fur was seen in animals of both
      groups (Flo58).
           MEKP (in dimethyl phthalate (DMP) as 45:55 w/w solution) was tested for
      its toxic effects following repeated dermal exposure for either 2 or 13 weeks in
      Fischer 344/N rats and B6C3F1 mice. In the 2-week studies, groups of 5 animals
      of each species and sex were treated with the solution at daily doses of MEKP
      of 50.6, 101.3, 202.5, 405, and 810 mg/kg bw (rats) or 112.5, 225, 450, 900,
      and 1800 mg/kg bw (mice), 5 days/week, for 2 weeks, plus 2 consecutive days
      in week 3 before terminal sacrifice. Control groups received DMP or no
      treatment. The solution was applied to the clipped dorsal skin, but the size of
      surface area used was not reported. Treatment did not cause mortality in rats,
      but in mice, mortality, attributed to the severe skin lesions at the application site,
      ranged from 1/10 animals at the lowest dose to 7/10 at the highest dose. In rats,
      there was a dose-related decrease in body weight gain. Final body weights
      relative to those of the DMP controls ranged from 96 and 98% for male and
      female rats, respectively, of the lowest dose group to 83 and 92% for male and
      female rats, respectively, of the highest dose group (no statistical analysis
      presented). In mice, body weight gain was not affected. The primary effects
      found in both rats and mice with respect to the skin were extensive coagulative
      necrosis of the epidermis and dermis, variable degrees of inflammation of the
      adnexa, and epidermal regeneration and hyperplasia at the application site.
      Generally, in both rats and mice, organ weight changes considered possibly
      biologically relevant included decreases in absolute and/or relative thymus
      weights and increases in absolute and/or relative liver weights (especially
      marked in mice), but histological changes were not found or reported in these
      organs. Treatment-related lesions considered by the author to be secondary to
      the dermal lesions included increased haematopoiesis in the spleen of rats and
      mice and increased myeloid hyperplasia of the bone marrow in mice, primarily
      at the higher doses (Zei93).
           In the 13-week dermal studies, groups of 10 rats and 10 mice of each sex
      were treated with doses of MEKP of 1.07, 3.57, 10.7, 35.7, and 107 mg/rat and
      0.357, 1.19, 3.57, 11.9, and 35.7 mg/mouse, 5 days/week, for 13 weeks, plus an
      additional 2 consecutive days in week 14 before terminal sacrifice. As was the
050-7 Methyl ethyl ketone peroxide
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<pre>      case in the 2-week study, the solution was applied to the clipped dorsal skin, but
      the size of the surface area used was not reported. All high-dose mice, 3
      high-dose female rats, and 1 female mouse in the 11.9 mg/animal group died or
      were sacrificed during the first week of the studies. Because of the severity of
      the skin lesions — similar to those seen in the 2-week studies —, exposure of
      the surviving rats and mice of the 2 highest dose groups was preliminary
      terminated. In the animals of these groups, no body weight and organ weight
      analyses were performed. For the other groups, results showed a dose-related
      decrease in body weight gains. Final body weights relative to those of the DMP
      controls ranged from 105 and 97% for the male and female rats, respectively,
      treated with 1.07 mg/animal to 87 and 95% for males and females, respectively,
      treated with 10.7 mg/animal (no statistical analysis presented). In female mice,
      body weight gain was not affected while in males, the final body weights of the
      animals treated with 0.357 and 3.57 mg/animal were 99 and 95% of those of the
      DMP controls, respectively. Skin lesions at the application sites involved a
      spectrum of necrosis, inflammation, and acanthosis (epidermal hyperplasia) in
      the remaining rats treated with 10.7 mg and mice treated with 3.57 mg,
      acanthosis and hyperkeratosis in the other rat groups, and acanthosis in the other
      mice groups. Organ weight changes were observed in the rats of the 10.7
      mg-dose group and the mice of the 3.57 mg-dose group only, and included,
      amongst others, increases in relative weights of the heart in male rats, of the
      (right) kidney in male and female rats, and of the spleen in male and female
      mice and decreases in relative liver weights in male and female rats.
      Histological (organ) lesions were almost exclusively found in the preliminary
      terminated groups, and included spleen and bone marrow lesions similar to
      those described in the 2-week study. The authors commented that no NOAEL
      for histological skin lesions could be determined from these studies, as lesions
      were observed with administration of daily doses as low as 1.07 mg for rats and
      0.357 mg for mice (Zei93).
      It has been known for more than a decade that MEKP is used in experimental
      medicine as a model compound for lipid peroxidation in in vitro and in vivo
      experiments (And85a, And85b, Cha88, Fra89, Lit81, Sku94, Sum84, War91).
      Most of these experiments addressed the interaction between MEKP and
      vitamin E, and all of the in vivo experiments were done by single dose
      intraperitoneal administration. Pretreatment of rats with vitamin E prior to
      MEKP administration has been shown to reduce the extend of lipid peroxidation
      in the animals. Reports on the effects of vitamin E on MEKP-induced damage
050-8 Health-based Recommended Occupational Exposure Limits
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<pre>      in the brain of rats were conflicting. Summerfield and Tappel showed a
      protective effect of dietary vitamin E against DNA cross-linking and
      protein-DNA cross-linking induced by MEKP (Sum84). However, Chaudiere et
      al. found no differences in the malonaldehyde levels in the brain of neonatal rats
      maintained on a vitamin E-deficient or -supplemented diet and exposed to
      MEKP by intraperitoneal injection. The only difference seen was a small
      decrease in GSH-reductase activity in the brain of vitamin E-supplemented rats
      (Cha88).
      The in vitro and in vivo experiments from Ando and Tappel are of interest since
      they found that MEKP damaged the cytochrome P450 peroxidase activity in rat
      liver. Destruction of cytochrome P450 haemoprotein and inhibition of its
      associated peroxidase activities increased as a function of time of exposure to
      MEKP (And85a, And85b). These results coincide with the dose-related increase
      of liver weights in vivo in mice in the 2-week dermal NTP study (Zei93).
      Carcinogenicity
      Zeiger et al. cited a study in which it was reported that MEKP induced
      malignant lymphomas in C57B1 mice, without giving information on treatment
      route and regimen and corresponding spontaneous tumour incidences (Zei93).
           Logani et al. studied the tumour-promoting activity of MEKP (50% solution
      in dibutyl phthalate) on the skin of hairless albino mutant mice
      (n=12/sex/group) in a two-stage initiation-promotion model. When ultraviolet
      radiation in the UVB region was used as a tumour initiator, a weak
      tumour-promoting activity was found when applying 10 µg/animal in acetone
      twice weekly. Dibutyl phthalate alone had no effect. The promoting activity of
      MEKP was enhanced by topical treatment with diethyl maleate that is known to
      deplete intracellular glutathione levels in several tissues among which mouse
      skin. The group that had been exposed to UVB initiation and promoted with
      diethyl maleate (20 µg/mouse) and MEKP had the highest tumour yield and the
      highest percentage of affected mice throughout the study. In general, all the
      qualified tumours produced in this study were papillomatous in appearance
      (Log84).
050-9 Methyl ethyl ketone peroxide
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<pre>       Mutagenicity and genotoxicity
       MEKP (45:55 w/w in dimethyl phthalate or with a purity of 60.8%) was not
       mutagenic when tested in 2 separate studies in S. typhimurium strains TA100,
       TA1535, TA1537 and TA98, with or without metabolic activating systems
       obtained from induced rat and hamster livers, at levels of 1 to 333 µg/plate
       (Mor86, Zei93). MEKP induced a weakly positive response when tested in both
       a plate and pre-incubation assay with S. typhimurium strain TA102, a strain
       reported to be sensitive to oxidative mutagens. At a concentration of 200 µg, the
       number of revertants per plate induced by MEKP was somewhat less than twice
       the number of spontaneous revertants. Furthermore, it was stated that the
       compounds tested among which MEKP showed a linear dose-response and that
       they did not require metabolic activation for their mutagenic response (no more
       details presented) (Lev84). MEKP (45:55 w/w in dimethyl phthalate) induced a
       dose-related increase in mutation frequency in mouse lymphoma L5178Y cells
       when tested at concentrations of 0.625 to 10 or 2 to 10 nL/mL in two separate
       trials in the absence of S9 activation (vehiculum: ethanol; not tested with S9). In
       cytogenetic tests with Chinese hamster ovary (CHO) cells, MEKP (45:55 w/w
       in dimethyl phthalate; vehiculum: dimethylsulfoxide) induced a dose-related
       increase in the frequency of sister chromatid exchanges (SCE) in the absence of
       metabolic activation (dose range: 0.5-16 and 2-15 µg/mL; doses ≥20 µg/mL:
       complete lethality). With metabolic activation, a positive response was seen
       only at the highest non-lethal dose tested (50 µg/mL). Similarly, a dose-related
       increase in the percentage of cells with chromosome aberrations was found
       without S9 while with S9 activation, a positive response was seen only at the
       highest non-lethal dose tested (Zei93). In an abstract without presenting details,
       it was reported that MEKP (in dimethyl phthalate) induced a ‘slight increase’ in
       SCE in CHO cells with and without metabolic activation (Jär84).
            In vivo, there was no increase in the frequency of micronucleated
       erythrocytes in peripheral blood samples obtained from male and female mice
       dermally treated with doses of MEKP of up to 3.57 mg/animal for 13 weeks
       (see above). Treatment did not cause changes in the ratios between
       polychromatic and normochromatic erythrocytes indicating that no overt
       toxicity was induced in the bone marrow cells (Zei93). DNA interstrand
       cross-links and DNA-protein cross-links were found in the brains of rats
       intraperitoneally treated with a dose of MEKP of 3.3 mg/kg bw and a second
       dose of 13 mg/kg bw one week later (and given 3-4 hours before sacrifice).
       These types of cross-links were both reduced by (pre-)treatment with vitamin E
050-10 Health-based Recommended Occupational Exposure Limits
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<pre>       (in the diet for a total of 12 weeks, including those weeks in which MEKP was
       given), suggesting MEKP induced cross-linking by generating free radicals
       (Sum84).
       Reproduction toxicity
       Daily dermal treatment of rats and mice with doses of MEKP up to 10.7 and
       3.57 mg/animal, respectively, for 13 weeks (see above), did not affect sperm
       morphology and vaginal cytology parameters (Zei93).
            Korhonen et al. (Kor83, Kor84) reported that MEKP was toxic to 3-day old
       chicken embryos, as indicated by increased mortality and malformations when
       the compound was administered into the air chamber. The median effective
       dose (ED50) was found to be 0.19 µmol MEKP/egg.
            The committee did not find other data on the potential reproduction toxicity
       of MEKP.
7      Existing guidelines
       The current administrative occupational exposure limit (MAC) for MEKP in the
       Netherlands is 1.5 mg/m3 (0.2 ppm), as a ceiling value.
            Existing occupational exposure limits for MEKP in some European
       countries and in the USA are summarised in the annex.
8      Assessment of health hazard
       The committee did not find adequate human studies in which exposure and
       effects to MEKP could be related.
            Human and experimental animal data indicate that MEKP is severely
       irritating to eyes and skin. A few cases of work-related allergic contact
       dermatitis with positive reactions to MEKP upon patch testing have been
       reported.
            Four-hour inhalation LC50 values of 1460 and 1240 mg/m3 (200 and 170
       ppm) were found for rats and mice, respectively. Effects on the nose and lungs
       were observed in these studies. The committee did not find other studies on the
       toxic effects of MEKP following single or repeated inhalation exposure or
       studies on repeated oral administration. In rats and mice dermally treated for 13
       weeks, there was mortality in 20/20 mice and in 3/20 rats (all females) at doses
       of 35.7 and 107 mg/animal, respectively. Because of severe skin lesions,
050-11 Methyl ethyl ketone peroxide
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<pre>       exposure of the surviving rats and of mice and rats of the next lower dose group
       (i.e., 11.9 and 35.7 mg/animal, respectively) were preliminary terminated. In the
       remaining mouse and rat groups treated with 0.357 to 3.57 and 1.07 to 10.7
       mg/animal, predominantly skin effects were seen at all these dose levels.
            MEKP (in dimethyl phthalate) was mutagenic in bacteria (S. typhimurium
       strain TA102) and mammalian cell systems (mouse lymphoma cells). It induced
       SCEs and chromosomal aberrations in CHO cells. In vivo, no increase in the
       frequency of micronucleated erythrocytes was found in peripheral blood of mice
       dermally treated for 13 weeks. DNA interstrand cross-links and DNA-protein
       cross-links were found in the brains of intraperitoneally treated rats.
            MEKP (in dibutyl phthalate) was weakly positive in a two-stage mouse-skin
       tumour initation-promotion model, but adequate studies on the potential
       carcinogenic properties were lacking.
            The committee did not find adequate data on the potential reproduction
       toxicity of MEKP.
       The committee considers the toxicological database on methyl ethyl ketone
       peroxide 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.
       References
ACG99  American Conference of Governmental Industrial Hygienists (ACGIH). Methyl ethyl ketone
       peroxide. In: TLVs® and other occupational exposure values - 1999. [CD-ROM]. Cincinnati OH,
       USA: ACGIH®, Inc, 1999.
ACG02a American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2002. Cincinnati OH, USA: ACGIH®, Inc, 2002: 84.
ACG02b American Conference of Governmental Industrial Hygienists (ACGIH). 2002 TLVs® and BEIs®.
       Threshold Limit Values for chemical substances and fysical agents. Biological Exposure Indices.
       Cincinnati OH, USA: ACGIH®, Inc, 2002: 42.
And85a Ando M, Tappel AL. Methyl ethyl ketone peroxide damage to cytochrome P-450 peroxidase
       activities. Toxicol Appl Pharmacol 1985; 81: 517-24.
And85b Ando M, Tappel AL. Effect of dietary vitamin E on methyl ethyl ketone peroxide damage to
       microsomal cytochrome P-450 peroxidase. Chem Biol Interact 1985; 55: 317-26.
050-12 Health-based Recommended Occupational Exposure Limits
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<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:
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Bou63  Bourne LB, Milner FJM. Polyester resin hazards. Br J Ind Med 1963; 20: 100-9.
Bhu97  Bhushan M, Craven NM, Beck MH. Contact allergy to methyl ethyl ketone peroxide and cobalt in
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CEC00  Commission of the European Communities (CEC). Commission Directive 2000/39/EC of 8 June
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       ofCouncil 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.
Cha88  Chaudiere J, Clement M, Gerard D, et al. Brain alterations induced by vitamin E deficiency and
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DFG02  Deutsche Forschungsgemeinschaft (DFG): Senatskommission zur Prüfung gesundheitsschädlicher
       Arbeitsstoffe. MAK- und BAT-Werte-Liste 2002. Maximale Arbeitsplatzkonzentrationen und
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Flo58  Floyd EP, Stokinger HE. Toxicity studies of certain organic peroxides and hydroperoxides. Am Ind
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Fra89  Fraga CG, Zamora R, Tappel AL. Damage to protein synthesis concurrent with lipid peroxidation in
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Fra90  Fraunfelder FT, Coster DJ, Drew R, et al. Ocular injury induced by methyl ethyl ketone peroxide.
       Am J Ophthalmol 1990; 110: 635-40.
HSE02  Health and Safety Executive (HSE). EH40/2002. Occupational Exposure Limits 2002. Sudbury
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Jär84  Järventaus H, Norppa H, Linnainmaa K, et al. SCE induction in CHO cells by peroxides used in
       plastic industry. Mutat Res 1984; 130: 249.
Kor83  Korhonen A, Hemminki K, Vainio H. Toxicity of rubber chemicals towards three-day chicken
       embryos. Scand J Work Environ Health 1983; 9: 115-9.
Kor84  Korhonen A, Hemminki K, Vainio H. Embryotoxic effects of eight organic peroxides and hydrogen
       peroxide on three-day chicken embryos. Environ Res 1984; 33: 54-61.
Lev84  Levin DE, Hollstein M, Christman MF, et al. Detection of oxidative mutagens with a new
       Salmonella tester strain (TA102). Methods Enzymol 1984; 105: 249-54.
Lit81  Litov RE, Matthews LC, Tappel AL. Vitamin E protection against in vivo lipid peroxidation
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       1981; 59: 96-106.
050-13 Methyl ethyl ketone peroxide
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<pre>Log84  Logani MK, Sambuco CP, Forbes PD, et al. Skin-tumour promoting activity of methyl ethyl ketone
       peroxide - a potent lipid-peroxidizing agent. Food Chem Toxicol 1984; 22: 879-82.
Mal57  Malten KE. Kunsthars-eczeem als bedrijfshygiënisch probleem. Ned Tijdschr Geneeskd 1957; 101:
       1319-25.
McG81  McGlothlin JD, Thoburn T. NIOSH health hazard evaluation report: HHE-79-012-809. Monroe OH,
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050-14 Health-based Recommended Occupational Exposure Limits
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<pre>             Annex
Occupational exposure limits for methyl ethyl ketone peroxide in various countries.
country                       occupational exposure            time-weighted       type of exposure notea     referenceb
-organisation                 limit                            average             limit
                              ppm            mg/m3
the Netherlands
-Ministry of Social Affairs   0.2            1.5               ceiling             administrative   -         SZW02
and Employment
Germany
-AGS                          -              -                                                                TRG00
-DFG MAK-Kommission           -              -                                                                DFG02
Great-Britain
-HSE                          0.2            1.5               15 min              OES              -         HSE02
Sweden                        0.2            1.5               ceiling                                        Arb00b
Denmark                        -             1                 ceiling                                        Arb00a
USA
-ACGIH                        0.2            -                 ceiling             TLV              -         ACG02b
-OSHA                         -              -                                                                ACG02a
-NIOSH                        0.2            1.5               ceiling             REL              -         ACG02a
European Union
-SCOEL                         -             -                                                                CEC00
a
     S = skin notation; which mean 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.
050-15       Methyl ethyl ketone peroxide
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<pre>050-16 Health-based Recommended Occupational Exposure Limits</pre>

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