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  • WHO-EM/CEH/129/A

    -2005

  • ii

    2000:

    Hazardous chemicals in human and environmental health (a resource book for school, college and university students) (WHO/PCS/00.1)

    ..

    .

    .

    ©2005

    ..

    . .

    .)7608(11371) :202 670 2535+:202 670 2492 + :int.who.emro@DSA .(

    ) :202 276 5400+ :int.who.emro@HBI.(

    asp.publication/ceha/int.who.emro.www://http

  • iii

    :

    :

    :)(

    :)(

    :)()(

    )(

  • iv

    iii

    ix

    x

    1-11-12

    1-1-121-1-22

    1-1-2-121-1-2-23

    1-241-34

    1-3-151-3-25

    1-4) (51-4-15

    1-4-1-151-4-1-261-4-1-361-4-1-46

    1-571-5-18

    1-5-1-181-5-1-28

    1-5-291-5-2-19

    1-5-3101-5-4111-5-511

    1-6121-6-1131-6-2131-6-315

    1-7151-7-1161-7-2171-7-3171-7-4171-7-518

    1-818

    2-212-1222-2222-324

  • v

    2-4252-4-1252-4-225

    2-5272-627

    3-313-1323-233

    3-2-1333-2-2343-2-336

    3-3363-4383-540

    3-5-1423-5-242

    3-6433-7463-848

    4-534-154

    4-1-1564-1-1-1564-1-1-257

    4-1-2574-1-2-158

    4-1-3594-1-3-1594-1-3-2614-1-3-362

    4-1-463

    5-675-1685-2685-3685-469

    5-4-1695-4-1-1695-4-1-2705-4-1-3705-4-1-470

    5-4-2705-4-2-1715-4-2-271

    5-4-3715-4-4735-4-5) (73

  • vi

    6-776-1786-2796-3796-4–80

    6-4-1806-4-2816-4-3) (816-4-4816-4-5826-4-6(IPM)826-4-782

    85

  • vii

    142637475869710812917

    1018112212351338144215451647174918(GV)61196220632168

    1525384115D.D.T136)(14716822923

    1026112712331334143515361637173918411942205521712272

  • viii

  • ix

    .

    . .100.000

    2,000 ..

    .

    .

    .

    . .

    . .

    .

    .

    .

    150/1992

    . .

    . .

    ..

    . ..

  • x

    ADIAQGCFCCNSDNAFAOGV

    HEIAIARCIPM

    JECFA

    JMPR

    LOAELNOAEL

    PAHPCBPVCTDI

    WHO

  • 1

    1.

    :

    .

    .

    .

    .

  • 2

    1-1.

    ..

    ..

    .

    ) (.

    .

    1-1-1

    ) () () .(

    ) (.

    1-1-21-1-2-1

    :)1 ()2 ()3 ()4 (.)1(0,5/

    95/.

    ..

    .2800/ .

    .0,5-1/.

    (Dental Fluorosis).

    .10/(Skeletal Flurosis)

    ..

    )2(.

    .4%.

    .

    .

  • 3

    )3( .

    ) (

    .)4(

    ..

    40/.

    1-1-2-2

    .150.

    .

    ..

    .1,5

    ..

    14/ . .

    0,01–200/.

    .0,270/.

    ..

    0,01/.:

    )(:

    1,8/

  • 4

    ..

    ) (.

    .

    .(IARC)).(

    ..)1(.

    1.

    (Cd).

    (Cr)

    (Pb):

    )(

    1-2..

    :

    )(:(Alkaloids).

    (Allergens).(Cyanogens).

    (Enzyme Inhibitors).(Glucosinolates).

    .

    )(:).(

    1-3(Foodborne intoxication)(Foodborne

    infection).

    .

    .

  • 5

    1-3-1) (

    . .

    .) (

    ).(80.

    .

    ..

    .

    1-3-2) (.

    .18-36) (

    )(4-8

    .) (.

    .)(.

    1-4) () (

    .) ((ergotalkaloids)")1 "((tricothecenes)

    (Fusarium)")2( "

    (Aspergillus)) (.

    1-4-11-4-1-1

    .(Aspergillus Flavus)

    (Aspergillus Parasiticus)(B1, B2, G1, G2).(B1)

    .

    //

    19878

    6 .

    .

    .

    36.

    .

    E

    ) (.

    )1(:

    )2(

    B2

  • 6

    . ..

    .

    1-4-1-2

    .

    .

    .

    .

    .

    ..

    1-4-1-3(B1)(hepato-carcinogen)

    .

    (B1)).(

    1-4-1-4.

    )2.(

    .

    2.---.--.--) ….(

    BG(B) :

    .(G) :

    .

  • 7

    1-5.

    ..

    ..

    .

    . .

    .

    (occupational exposure).

    .)3(

    )4.(

    3.)(

    –X

    )()

    (

    .

    4.¹

    *********-*--*--**************

    )(*********-**

    ¹.

  • 8

    1-5-1

    ..

    30,000..

    ..)

    (..

    1-5-1-1.

    .

    .40%.

    .

    ..

    .

    1-5-1-2

    .)(

    ..

    5 . /

    1930-195019511952195640

    1957-1958

    19591960-196311141

    19661970) (

    1973-19751603226

    1930-1960

    .

    ) (

    .

    .5 .

    )3(

  • 9

    1-5-2

    .8000.

    ..

    .20.

    .

    . .

    ..

    ..

    1-5-2-1.

    .

    ) (.

    .

    .) ((Dermatitis)

    ..

    .)(

    .)6.(

    .

    6 .

    : ) (Bysinnosis :)(

    /

    )7.(.

    ..

    .

  • 10

    .

    .) (

    .

    1-5-3)(

    ..

    .)(.

    (3MgO.2SiO2.2H2O)90% ..

    7

    )(pH

    pH

    3,1-2-

    pH

    pH

    )3,2 (

    (mesothelioma).(asbestosis)

    .

  • 11

    .

    1-5-4

    .2500

    ..

    ..

    .) (

    (PAHs))4.(

    ..

    .

    ) (

    ..

    ..

    .)8.(

    .

    1-5-5.

    . .)(

    ..

    42.(aplastic anaemia)

    .

    ..

    )4(

  • 12

    8.

    ) (AluminaAluminum chlorideAmines, aliphaticAmines, aromatic

    )(AmmoniaArsenic compoundsAsbestos

    ) (Bitumen fumesTert-Buty1 alcohol) (Chromium and its compoundsCobalt and its compoundsCoke)(Copper and its compoundsCrude oilHydrocarbons, aromaticHydrogen chloride)) (

    (Hydrogen fluorideHydrogen sulfide KetonesLead and its compoundsMineral oilsNickel and its compoundsNitrogen oxides)(PalladiumPhenol PitchPhosphoric acid Platinum Polynuclear aromatic hydrocarbons (PAHs)

    )(

    Petroleum solventsSulfuric acid TetraethylleadVanadium compounds

    1-6

    ) ().(..

    ) (.

    ..

  • 13

    1-6-1

    .) ()6(.

    .

    .. .

    .

    .(DDT))5(

    ." ".

    “Phenoxyacid”.

    1-6-2.

    ..

    . .

    .

    :...

    ..

    .

    )5(DDT

  • 14

  • 15

    1-6-3

    .

    .

    ..

    .

    ..

    .

    .

    .

    1-3/.1-9 %.

    ) (.

    ..

    ..

    .

    .

    .

    .

    1-7)

    7.(..

    .

    .

  • 16

    .

    ..

    1-7-1

    ..

    ) ( .

    .198696) (

    10%2%.

    .

    )7 (

    1997

    )(

    .

    20,000.

    234.

  • 17

    1-7-2

    )9 (.

    (SO2))NO2 , NONOx ((CO)(O3)

    (SPM)(Pb).

    9.

    ) : ((NO2 , NO) NOx , SOx

    :) ( :) ((SO4),

    (NO3)SO2-2)(

    )(SO2)) ((SOx)(NOx.

    )(NOxCOPb)(.

    .

    1-7-3

    ) (.

    (VOCs).18.

    ) (

    .

    .(Phytotoxic)

    .

    1-7-4

    .

    .

    ) :.(

    .

    .) ()

    Polychlorinated dibenzo-dioxinsdibenzo-furans

    _

  • 18

    PAHs ().(

    )" (".

    1-7-5

    ..

    /)2 (..

    ...

    1-8

    .

    ..

    ..

    )10 (.

    10.¹

    1974)(28

    19762,3,7,8-tetrachloro-dibenzo-p-

    dioxin

    )(

    1979)(200,000

    1984/)(50050001984isocyanate)(2500200,0001986)(1986)(1000

    ¹

    .

    1967

    100,000 .

    ExxonValdez1989.

    40

    70002

    250.

  • 19

    :

    ..

    . .

    .

    .

  • 20

  • 21

    2.

    :

    ..

    ..

  • 22

    2-1

    ..

    .

    :)()()(

    .)9 (.

    2-2

    ..

    ..

    ..

    ..

    ..

    .)11.(

    ..

    ...

    .

    11 .

    Paraquat, captafol, 2,4-D, mancozeb )(Beomy1, DDT, lindane, zineb, malathion Hexachlorobenzene, benomy1, zineb Organochlorine pesticides )(Hexachlorobenzene

    :

    ..

    .

    )8(

  • 23

  • 24

    ) (.

    ..

    ) … () ()

    :.(.

    3-6.

    . .

    .

    )3.(

    2-3

    ..

    .

    .

    .) (.)

    () ().(

    .) (

    .

    .

    ..

    .

    .

    .

    .

    /1952

    .3500 -

    4000

    ) (

    .

    .

  • 25

    .

    .

    .

    ..

    .

    ..

    .

    2-4

    ..

    )10.(

    2-4-1

    .

    .) ( .

    2-4-2

    .

    ..

    .

    1981

    20,000

    340.

    .

    .

  • 26

    )10 (

    370“BlackFoot”428.

    .

    50-60..

    .)(

    ) (.700.05/..

  • 27

    30.

    -.

    200,000.

    .

    ..3

    ..

    .

    2-5

    ..

    .) (

    ..) (

    ..

    ..

    .

    ..

    .

    “Biotransformation”. ..

    .

    2-6

    . .

    ..

    )11.(

    .

    .

    )11(

  • 28

    :.

    :.

    .)3+3=6.( :

    ..

    .)3x3=9.(:.

    ..)3-2=1.(

    .(dimercaprol)

    .

    .

    ).(

    ).(.

    .

    .

  • 29

    :

    :) () ().(

    .

    ..

    .

    .

    .

    .:

    . :

    .:

    .) : (

    .

  • 30

  • 31

    3.

    :

    .

    .

    .

    .

    .

  • 32

    3-1

    ..

    .

    )5.( .

    )(.

    ./

    . .) (

    ..

    24..

    ) (.

    ." "" ") .() (

    10-20..

    .)(.

    .)

    () ().(

    ) () ()

    () (..

    ) (.“Local Effect”

    “Systemic Effect".

    ).( .

    .) (.

    ..

    ..

    .

  • 33

    ) (.

    ..

    ..

    .) (

    .

    3-2.

    .“Inhalation Toxicology"

    “Respiratory Toxicology".

    .

    .

    3-2-1)

    (.

    )) (13.(

    .)

    .( .

    )12.() (

    .

    .).(

    .

    . .

    ) (..

  • 34

    .) (“mucociliary clearance” .

    3-6.

    )13(

    3-2-2.:

    )(.)(.)() (.

    .) (.

  • 35

    )(..

    .

    .5-30

    )(.1-5

    ).() (3-2-1.

    .1.

    ) ()14 (.

    ) (.

    )12 (.

    12.

    )(

    ).(.3

    ).(

    .) (.

    .).(

    ..

    .

    30-5

    )(

    5-1

    1

    )14(

  • 36

    3-2-33-7

    ..

    40-70.80%.

    ..

    .

    .)

    .()

    .(

    ...

    .

    20-50.

    .

    ..

    .

    ..

    .)15(.

    3-3)16.(

    ..

    ..

    ) (..

    .

    )15(

  • 37

    )16(

    (Hepatocyte))()

    ()()

    .(.

    ..

    .)Hepatotoxicants (

    :)13(.)Steatosis (

    ..) (

    ..

    .(PCBs) (Polychorinated biphenyls)

    ..

    )(

    : :

    . :

    .

  • 38

    13.

    (necrosis)(steatosis)Allyl alcohol+Allyl formate+Aflatoxin++Beryllium +Bromobenzene +Bromotrichloromethane ++Carbon tetrachioride ++Cerium +Chloroform ++Cycloheximide +Dimethylaminoazobenzene ++Dimethylnitrosamine ++Ethanol+Ethionine+Galactosamine ++Mithramycin +Phosphorus ++Puromycin +Pyrrolizidine alkaloids ++Tannic acid ++Tetrachoroethane ++Thioacetamide +Trichloroethylene ++Urethane +

    (Angiosarcoma).)Metastasis (

    .3-7.

    3-4)- (

    . .

    .(electrolytes)) (

    ).(.

    .)17 () (“nephron”.

    ..) () () (

    .) (.21%

    ..

  • 39

    ..) (

    ..

    ..

    )17(

  • 40

    (nephrotoxicants):

    )(

    .)(.)(.)(.

    70 %(electrolytes).

    .(electrolytes)

    ..

    ...

    ..24-48.

    .

    ).(

    ) .(

    .

    .

    3-5.

    )18 ( .

    ...

    .

  • 41

    )18 (

    . …

    ..

    . .

    ..

    ..

    .

    : . :

    .

  • 42

    3-5-1)19 (

    ) (..

    “neurotransmitters”..

    ) (“myelin”.) (.

    ..

    “blood brain barrier".

    .

    . .

    ..

    ) ().(

    3-5-2

    .)14 ( .

    14.kanamycin

    kainate

    azide

    ..

    .)()(

    ) (..

    .. .

    )19() (

    )(

  • 43

    ..

    .

    ..4006000

    .

    "“as mad as a hatter” .

    .

    (CS2).

    1776..

    )( ..

    ) (.

    .

    .

    ..

    ..

    ..

    3-6

    .

    ) (..

    “Immunotoxicants”. :

    ).( :

    )Leukocytes (.

    :

    ) (

    .

  • 44

    ) ((Neutrophils)(Macrophages)..

    .(Phagocytosis)

    ..

    .) (.

    " "“antibody”.520

    .100 .

    ) (.

    TB.(B)..

    ..(B).

    .

    .

    ..

    .(immunosuppression)

    ..

    ..)

    ( .(Polychlorinated biphenyls)

    .)15 (

    .

    : *. *. *.

  • 45

    15.

    (carbamates, organochlorines,

    organophosphates)

    AzodyesBHTBHA

    EDTAmercurials(toluene diisocyanate, trimellitic anhydride)

    (allergicreaction).

    ).(.

    .B" "

    ...

    ..

    ..

    ..

    .

    ..

    ..

    ..

    .

  • 46

    .

    ...

    .. .

    .

    ..

    ..

    3-7

    ).(

    ).(

    .)Spermatogenesis.(

    ..

    ) (15%.

    3%.) (.

    .) .(

    ) (..

    .(teratogens).

    ) (.

    .) : (.) (.) (.) (.

    .

    .20-70.

    ) (..

    ..

    .

    ) (

    .

  • 47

    )16.(

    16.

    AldrinArsenic

    Benzene

    Cadmium

    Carbon disulfide

    Chlorinated ompounds ) (

    2,1–3–1,2-Dibromo-3-chloropropaneDichloroethylene)(Dieldrin

    Hexachlorocyclohexane

    Lead.

    Mercury

    Polycyclic aromatic hydrocarbonsPolychlorinated biphenyls

    Trichloroethylene)(

    ..

    . .

    ..

    .

    .

    .

  • 48

    3-8.

    ..DNA

    (deoxyribonucleic acid)) (.(DNA)

    ..(DNA)

    ) () ( .

    ...

    ..

    .) (Neoplasm.

    “Benign”.

    “malignant”..

    .

    .) (metastasis.

    ..

    .:

    )( :..

    DNA.)( :

    “neoplasms”.)( :.

    ) ().(

    ..(IARC)

    35.“mutagens”DNA .

    .

    .)17 (.

    :*

    .*

    .

    : *. *. *.

    .

  • 49

    17.2-2-aminonaphthalene4-4-aminobiphenyl5-5-azacytidine

    AflatoxinsAlcoholArsenicBnzeneBenzidineChromium compoundsCoal tarsMineral oilsNickel compoundsNitrogen mustardShale oils

    )(SootSulfur mustardTobacco smokeTreosulphantriethylenethiophosphoramideVinyl chloride

    PVC(Polyvinyl chloride).

    PVC ..197440

    .PVC

    . .

    ...

    ..

    .30%.

    (nitrosonornicotine).

    (PAHs).

  • 50

  • 51

    :

    .

    .

    24

    3..

    .

    .

    (lipophilic)) (.

    .. .

    .

    .

    .

  • 52

  • 53

    4 .

    :

    .

    .

    (NOAEL):.

    (TDI):.

    (ADI):.

    .

    .

    .

  • 54

    .

    ...

    ..

    .."

    "“dose-effectrelationship"“dose-responserelationship".

    ..

    .

    .

    .

    ..

    ..

    "".

    . .

    .

    .) : (

    /.) (.) (

    .) (.) () (.

    .

    4-1

    .. .

    .

    =×.

    .

    . *

    . *

    . *

    .*

    . *

    .

  • 55

    )(.

    .

    .)20 (

    ." "

    .–-..

    )20(–

    –-)20(..

    .

    ](bronze diabetes)[

    .

    .

    1493-1541

  • 56

    .“Paracelsus”)1493-1541 (–.

    .

    .“NOAEL”.

    ..

    ) .(

    .–

    -“LOAEL”.“LOAEL”

    ..

    .

    .

    .

    ."

    .") (.

    .

    ." "VSD

    .VSD

    ." ".

    4-1-14-1-1-1

    ]tolerable daily intake[(TDI).

    (TDI).

    NOAEL

    .

    .

    .

  • 57

    4-1-1-2

    .

    ..

    .

    .

    ..4-1-3-1.

    100NOAEL)

    " "(1010

    .100

    )3(.100.

    NOAEL–)(

    .5000-10000.

    ..

    )10 (.

    .10.

    4-1-2(TDI)TDI

    .TDI

    ..

    TDI.TDI

    TDI.

    .TDI.

    (TDI)

    .

  • 58

    4-1-2-1

    ..TDI

    ..

    . .

    )18(

    . .

    .

    .

    –(genotoxicity).

    .

    .

    .)(

    .

    )

    (.

    :1 :

    ).(

    2 :)

    acrylonitrilebenzo[a] pyrene.(

    2 :.

    )DDTsaccharinurethane.(

    .)

    .(

  • 59

    3 :)

    manebzineb(.

    4:

    )caprolactam(.

    4-1-34-1-3-1

    WHO1993.120

    95.:

    ..

    ).(

    ..

    :(TDI)

    .(TDI)NOAELLOAEL.

    (TDI).

    ).(:

    NOAEL TDI=UF

    (TDI) (bw) P GV=C:

    NOAEL :–.

    NOAEL(LOAEL)(UF).LOAEL

    .(UF)NOAELLOAEL

    (TDI).

    (case – by – case) .110,000. :

  • 60

    )(1–10

    )(1–10

    1–10

    1-10

    10,000(TDI).

    .

    TDI = –)/ (

    .bw = ) (–60.

    510.P = (TDI) .

    .0.011.

    10%(TDI).

    C = –21100.755.

    GV = .

    )(.

    60270 .

    100,00070.

    .

    10.

    ..

    ..

    .)18 (

    (WHO).

  • 61

    18 .(GV)

    )/(0.016×10 -4

    )(0.003-1.5

    .0.01

    .)(0.001-

    501 20.0310 .

    DDT0.002-0.2-

    4-1-3-2 .

    .)

    (.

    .

    ..

    .

    ..

    .

    )(.Air Quality Guidelines

    (AQG).(AQG)

    .

    )4-1-2-1(..

    .

    )(.(AQG).

    .

    .

    -5

  • 62

    .

    .

    4-1-3-3

    (LOAEL).(NOAEL).

    (LOAEL)(NOAEL).

    . .

    .

    ..

    .

    ..

    .)5-3(.

    (AQG)

    .

    ..

    ..

    )19 ()20(.

    19.

    100/360/330/310/3

    1530

    80.5-1/3

    400/3150/324

    150-200/3100-120/38

    500/3350/3

    10

  • 63

    20.

    Acrylonitrile2 × 10-5

    4 × 10-3

    4 × 10-6)((VI)4 × 10-2

    4 × 10-4

    1 × 10-6

    1/3

    4-1-440

    .(WHO)(FAO)

    (JECFA)(JMPR)

    .

    (ADIs)(Codex Alimentarius Commission)

    .(JECFA)(JMPR)

    )()

    (.

    (teratogenicity)..

    (NOAEL)(NOAEL)

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  • 64

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  • 65

    :

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  • 66

  • 67

    5 .

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  • 68

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  • 69

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  • 70

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  • 71

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  • 72

  • 73

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  • 74

  • 75

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  • 76

  • 77

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  • 78

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  • 79

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  • 80

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  • 81

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  • 82

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  • 83

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  • 84

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  • 85

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  • 86

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  • 87

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  • 88

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