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MALATHION 217 Sample matrix Human blood Human blood 7. ANALYTICAL METHODS Table 7-1. Analytical Methods for Determining Malathion or Biomarkers of Exposure in Biological Samples Preparation method Collection of blood samples, 0.1 M phosphate buffer (pH=8.0) Collection of blood samples, tris(hydroxymethyl)aminomethane, sodium chloride, HCl, centrifuge Blood Microtiter assay using acetylthiocholine, AChE, Ellman assay reaction mixture Human serum Human urine Human urine Human urine Human urine Analytical method Spectrophotometer (at 410–412 nm) Colorimeter analysis (at 412 nm) Microtiter assay; absorbance measurement (at 405 nm) Sample detection Percent limit recovery Reference No data No data Ellman et al. 1961 No data No data Knaak et al. 1978 No data No data Doctor et al. 1987 Extraction with hexane GC-FPD 0.001 mg/L No data Fournier and Sonnier 1978 Extract with diethyl ether, centrifuge, acidify, extract with hexane, alkylate with BF3-methanol, purify on silica gel (elution with benzene/ethyl acetate Hydrolysis of MCA and DCA with 1.0 N KOH, 90 C, 4 hours, extraction with hexane, derivatization with PFBB Solid-phase extraction, methanolic HCl extraction, derivatization with diazomethane, Acidify to pH 3.7, extract twice with CH2Cl2/diethyl ether (1:4), centrifuge and concentrate GC-FPD 0.002 mg/L (DCA) 0.005 mg/L (MCA) GC-FPD (phosphorous mode) Isotope dilution Ion Trap GC-MS Isotope dilution HPLC/MS/MS 0.014 mg/L (DMTP) 0.025 mg/L (DMDTP) 6.5 ng/mL (DCA) 4.4 ng/mL (MCA) 0.5 µg/L (DCA) 98–101% for DCA 98–104% for MCA 88% (total malathion) 120% (DMTP) 70% (DMDTP) 106–114% (DCA) 50–60% (MCA) Bradway and Shafik 1977 Fenske and Leffingwell 1989 Draper et al. 1991 75% Baker et al. 2000; Beeson et al. 1999 DCA = malathion dicarboxylic acid; DMDTP = O,O-dimethyl phosphorodithionate; DMTP = O,O-dimethyl phosphorothionate; FPD = flame photometric detection; GC = gas chromatography; HCl = hydrochloric acid; HPLC = high performance liquid chromatography; KOH = potassium hydroxide; M = Molar; MCA = malathion monocarboxylic acid; MS = mass spectrometry; PFBB = pentafluorobenzyl bromide
MALATHION 218 7. ANALYTICAL METHODS pentafluorobenzyl bromide. However, the procedure is not specific for malathion since DMTP and DMDTP are common to several types of organophosphorous insecticides. The detection limits were 0.014 mg/L for DMTP and 0.025 mg/L for DMDTP. Ion-exchange resins and anion-exchange solidphase extraction have been used to isolate metabolites of malathion from urine (Lores and Bradway 1977; Muan and Skare 1989). The MCA, DCA, DMDTP, and DMTP metabolites were derivatized with diazomethane and assayed using GC-nitrogen-phosphorus-detection (NPD). A detection limit of 2 µg/mL for each metabolite was reported. A later modification of this procedure utilized isotope dilution ion trap GC-MS to detect the diazomethane derivatives to improve the detection limits. The lowest limits of detection for DCA and MCA were 0.006 and 0.004 mg/L, respectively. A recent method for identifying and quantifying malathion diacid in urine samples collected from nonoccupationally exposed populations utilizes isotope dilution high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS); the method has the advantage of not requiring derivatization of DCA ( Baker et al. 2000; Beeson et al. 1999). Using this method, urine samples are acidified (10% sulfuric acid) to a pH of 3.7 and extracted with methylene chloride and ethyl ether (1:4). The organic extracts are combined and concentrated for HPLC injection and MS/MS analysis. The analytical limit of detection was 0.0005 mg/L and the recovery was 75%. The advantages of this technique are the high specificity and sensitivity that are achieved by chromatographically separating out unwanted contaminants that could interfere with the mass analysis and the use of isotope dilution to correct for sample recoveries. The most commonly used assay for determining ChE activity is that of Ellman et al. (1961). In this method, RBCs are suspended in a buffer (e.g., 10 µL blood in 6 mL of 0.1 M phosphate buffer). For assay of only RBC ChE, the suspension is treated with quinidine sulfate to inhibit PChE. Total esterase activity is determined in the samples with no addition of quinidine sulfate. The production of thiocholine formed in the hydrolysis of acetylthiocholine is measured by coupling of the reactive thiol with 5,5'-dithio-bis(2-nitrobenzoate) (DTNB) to give a thionitrobenzoate (TNB). The TNB is a yellow anion and its formation can be measured spectrophotometrically. The production of TNB is rapid and the concentration of DTNB used in the assay does not inhibit the enzyme. Absorbance is typically measured at 410–412 nm, but other wavelengths have been used. Because a nonlinear reaction of the thiol reagent with reduced glutathion of RBCs is possible, a sample blank is required. This method has been adapted to assay cholinesterase in other tissues such as lung, brain, liver, stomach, heart, and muscle. An adaptation of the Ellman assay is a microtiter assay method for AChE that has been developed by Doctor et al. (1987). The AChE samples to be assayed are added to microtiter plates and enzymatic hydrolysis is
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TOXICOLOGICAL PROFILE FOR MALATHION
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MALATHION iii UPDATE STATEMENT A To
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MALATHION viii Managing Hazardous M
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MALATHION xi PEER REVIEW A peer rev
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MALATHION xiv 3.2.3.2 Systemic Effe
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MALATHION xvii LIST OF FIGURES 3-1.
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MALATHION 1 1. PUBLIC HEALTH STATEM
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MALATHION 11 1. PUBLIC HEALTH STATE
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MALATHION 14 2. RELEVANCE TO PUBLIC
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MALATHION 24 3. HEALTH EFFECTS oral
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MALATHION 26 3. HEALTH EFFECTS sing
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≤
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MALATHION 30 3. HEALTH EFFECTS Resp
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MALATHION 32 3. HEALTH EFFECTS Rena
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MALATHION 34 3. HEALTH EFFECTS Stud
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MALATHION 36 3. HEALTH EFFECTS Fran
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MALATHION 38 3. HEALTH EFFECTS more
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MALATHION 40 3. HEALTH EFFECTS the
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a Key to figure 1 2 3 4 5 6 Species
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a Key to figure 15 16 17 18 Species
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a Key to figure 24 25 26 27 28 29 S
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a Key to figure 40 41 42 43 44 45 S
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a Key to figure 55 56 57 58 59 60 S
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a Key to figure 67 68 69 70 Species
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a Key to figure 83 84 85 86 87 88 8
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a Key to figure 91 Species (Strain)
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a Key to figure 93 94 Species (Stra
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≤
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≤
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MALATHION 64 3.2.2.2 Systemic Effec
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MALATHION 66 3. HEALTH EFFECTS 1965
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MALATHION 68 3. HEALTH EFFECTS Hepa
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MALATHION 70 3. HEALTH EFFECTS appr
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MALATHION 74 3. HEALTH EFFECTS Meta
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MALATHION 82 3. HEALTH EFFECTS Clin
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MALATHION 84 3. HEALTH EFFECTS mala
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MALATHION 86 3. HEALTH EFFECTS Tera
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MALATHION 88 3. HEALTH EFFECTS for
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MALATHION 90 3. HEALTH EFFECTS sugg
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Species (Strain) Systemic Exposure/
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MALATHION 94 3. HEALTH EFFECTS Endo
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MALATHION 96 3. HEALTH EFFECTS Othe
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MALATHION 98 3. HEALTH EFFECTS derm
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MALATHION 100 3. HEALTH EFFECTS al.
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MALATHION 102 3. HEALTH EFFECTS of
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MALATHION 104 3. HEALTH EFFECTS per
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MALATHION 106 3.4.1.1 Inhalation Ex
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MALATHION 108 3. HEALTH EFFECTS was
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MALATHION 110 3. HEALTH EFFECTS fir
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MALATHION 112 3.4.2.3 Dermal Exposu
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MALATHION 114 3. HEALTH EFFECTS neu
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MALATHION 116 3. HEALTH EFFECTS aci
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MALATHION 118 3.4.4.1 Inhalation Ex
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MALATHION 120 3. HEALTH EFFECTS agr
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MALATHION 122 V E N O U S BLOOD 3.
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MALATHION 124 3. HEALTH EFFECTS Tab
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MALATHION 126 3. HEALTH EFFECTS mus
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MALATHION 128 3.5.2 Mechanisms of T
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MALATHION 130 3. HEALTH EFFECTS pla
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MALATHION 132 3. HEALTH EFFECTS In
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MALATHION 134 3. HEALTH EFFECTS Ove
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MALATHION 138 3. HEALTH EFFECTS whe
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MALATHION 140 3. HEALTH EFFECTS the
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MALATHION 142 3. HEALTH EFFECTS org
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MALATHION 144 3. HEALTH EFFECTS The
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MALATHION 146 3. HEALTH EFFECTS pla
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MALATHION 148 3. HEALTH EFFECTS org
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MALATHION 150 3. HEALTH EFFECTS stu
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MALATHION 152 3. HEALTH EFFECTS Par
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MALATHION 154 3. HEALTH EFFECTS exp
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MALATHION 156 3. HEALTH EFFECTS wer
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MALATHION 160 3. HEALTH EFFECTS Lee
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MALATHION 162 3. HEALTH EFFECTS res
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MALATHION 164 3. HEALTH EFFECTS inf
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Page 257 and 258: MALATHION 238 9. REFERENCES *Agency
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Page 261 and 262: MALATHION 242 9. REFERENCES *Brown
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MALATHION 268 9. REFERENCES *Prabha
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MALATHION 270 9. REFERENCES *Roy RR
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MALATHION 272 9. REFERENCES *Singar
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MALATHION 274 9. REFERENCES *Thongs
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MALATHION 276 9. REFERENCES Viccell
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MALATHION 278 9. REFERENCES Yess NJ
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MALATHION 280 10. GLOSSARY Ceiling
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MALATHION 282 10. GLOSSARY Mutagen
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MALATHION 284 10. GLOSSARY Risk—T
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MALATHION A-2 APPENDIX A are not ex
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MALATHION A-4 APPENDIX A Was a conv
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MALATHION A-6 APPENDIX A Was a conv
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MALATHION A-8 APPENDIX A If an inha
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MALATHION A-10 Uncertainty Factors
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MALATHION B-2 Interpretation of Min
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MALATHION B-4 APPENDIX B (8) NOAEL
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1 2 3 4 12 → → → → → Key
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MALATHION C-1 APPENDIX C. ACRONYMS,
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MALATHION C-3 APPENDIX C MFO mixed
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MALATHION C-5 > greater than $ grea
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