??????????????1975?,????????????????1983????????????????????????????(National Research Council of the National Academy of Sciences, NAS-NRC)??????????

1
??????
2
1. ????????
3
??????

• ?????????????????????????????????????
• ????????????????????????????????????????????????,?
  ???????????????????????????

4
????????(I)

• ?? -
• ??????????????1975?,????????????????1983???????
  ?????????????????????(National Research Council
  of the National Academy of Sciences,
  NAS-NRC)??????????

5
?? -
????????(II)

• ???????????(92.01.08)? ?? ?
• ?????????????,??????????????
  ????????,??????????????????????,
  ???????????????,????????????

6
?????????

• ???????
• ?????????
• ??????
• ?????????
• ??????
• ?????????
• ?????????
• ?????????
• ?????????

7
???????????

• ??????????
• ?????????
• ??????????
• ???????
• ?????????

8
?????????

• ????????????
• ??????
• ???????????????
• ??????????
• ?????????

9
???????????

• ???? (Hazard Identification)
• ???? (Toxicity Assessment)
• ???? (Exposure Assessment)
• ???? (Risk Characterization)

????? ????????,??????,???????????????????
10
??????????????
11
?????????

• ?????
• ????
• ????

????

• ????
• ??????
• ?????

12
2. ????

• --??????????????????????

13
???????

• ??????????????????,????????????????????????????
  ??????????,????,?????????????,????????????

14
???????

• ????????,?????,?????????????????????????????
• ?????????,????????????????,??????????????????????
  (in-vitro test) ?????????????????????

15
???????

• ???????????????
• ??
• ????
• ????
• ????????????
• ??????????
• ???????????????

16
?????????????????????????????????????????,??????
??????????
??????????
????? ????? ?
???? ??
?????? ?
?????????
???? ?
17
??????????

• ???????
• ?????????
• ??????

18
????????

• ???
• ???
• ???
• ???????
• ??????????
• ??????(??/??)
• ??????
• ?? / ??????

• ?? / ????????
• ??
• ??
• ??????
• ???????
• ?????????
• ?????(??/???/??)

19
??????

• ???????
• ????
• ?????
• ????(??)
• ????
• ???
• ??????
• LD50?????
• LC50?????
• ???????
• ?????????

• ???????
• ????
• ????
• ????????
• ????????
• ??????
• ?????????
• ????
• ????
• ???
• ??????????

20
?????????????(I)

• ?? / ???????
• ???????
• ??????
• ?????
• ???
• ????
• ????
• ??????????

21
?????????????(II)

• ?????????
• ??????
• ??????????
• ???????
• ?????????
• ???????
• ????????????
• ????????

22
3. ????(Toxicity Assessment)

- ????????????????????????
23
???????
?????????? ?????????? -
Paracelsus (1493-1541)
??????????????????
24
???????

• ????????????,???????????????,???????????????????
  ??
• ??????????????(1)?????????????,?????????????????
  ???(2)??????????????(3)?????????????,?????????????
  ??

25
????

• ???????????(systemic toxicant)?????
  (noncarcinogen) ???????????????
• ????(Reference DoseRfD) ?????????(mg/kg-day),????
  ???????????????????
• ????????(RfD)???10???????
• ????(RfD)?????????(threshold)

26
????
????(RfD) ??????????,??? ?????????????(level),??
??? ????????
NOAEL
RfD
LOAEL
27
??????????

• UFLOAEL-NOAEL 10
• UFINTERSPECIES (???) 10
• UFSUBCHRONIC-CHRONIC (???-??) 10
• UFHUMAN VARIABILITY (?????) 10
• UFDATABASE INSUFFICIENCIES (?????) 10
• MF 1- 10

MF ??????????????
28
????

• ????????,????????????,???????,???????????????,?
  ??????? ????????,?????????????????????????????????
  (Carcinogens) ?

29
???

• ????????????????????(Cancer Slope Factor CSF)???
• ??????????????/??(Risk / Dose)? Risk/(mg/kg-day)
  ?
• ?????????( Threshold)?

30
???????-????
31
??????????(I)

• ??????????????????????
• ??????????40-50 ??? ??????????(the lowest cancer
  risk observable)?1/50 ,??,?????????????????
• ?????????????????????

32
??????????(II)
????(species)????????

• ????
• ??? (?2???????????70??????)
• ??
• ????
• ???????

33
???? Cancer Potency Factors
??? ???? per mg/kg/d ???? per mg/kg/d
Arsenic A 1.8 50
Benzene A 2.9 x 10-2 2.9 x 10-2
Benzo(a)pyrene B2 12 6.1
Cadmium B1 - 6.1
Chloroform B2 6.1 x 10-3 8.1 x 10-2
Chromium VI A - 41
Dioxin B2 1.6 x 105 -
1,1-Dichloroethylene C 0.58 1.2
1,1,1-Trichloroethane D - -
34
??????

• ????(Laboratory Animal Studies)
• ?????(Acute toxicological studies)
• ?????( Chronic toxicological studies)
• ????(Genotoxicity)
• ????(Immunotoxicity)
• ????(Developmental Toxicity)
• ????(In vitro studies)
• ????(Human Studies)
• ??????(Epidemiological Studies)
• ????(Case Studies)

35
??????

• IRIS ???????? ( Integrated Risk Information
  System ), US EPA
• HEAST ???????(Health Effects Summary Table), US
  EPA
• Provisional Values from National Center for
  Environmental Assessment (NCEA) , US EPA
• ??ATSDR(??????????) Chronic Minimum Risk Levels

36
4. ???? (Exposure Assessment)

• -- ??????????????????,?????????????????????

37
???????

• ??????????????????????????????????????????????????
  ?(exposure scenarios),?????????????????,??????????
  ????????,???????????,????????(Most Exposed
  population)???????????????????????

38

• ???????? ?
• ??, ??, ????, ????
• ?????? ?
• ??, ??, ????
• ?????? ?
• ppm , ?g/m3
• ????????? ?
• ?/?, ????

39
????????????
??????
????
????
???????
????
????
????
????
????
??????
????
?????
40
???????-???

• ??????
• ???? (Biological Monitoring)
• ??????????????????????????????????????????????,??
  ???????,???????????

41
????????

• ???????????????????????
• ?????????????????????????????????????????,????????
  ????
• ?????????????
• ??????????
•  

42
- ???- ?????????- ????- ????????
???????
???????

• ???? (Exposure Pathways)
• - ????
• - ????
• - ??????

43
??????

• ????????DI (mg/kg-day)??????
• DI (Ca ? IH ? ET)/BW
• ??
• Ca ????????????,mg/m3
• IH ?????,m3/hr
• ET ??????,hr/day
• BW ??,kg

44
?????????????
NIOSH 1976
45
??????

• ????????DI (daily intake ,mg/kg-day)??????
•  
• DI (Cw ? Iw)/BW
• ??
• Cw ?????????,mg/L ? mg/kg
• Iw ??????,L/day?kg/day
• BW ??,kg

46
????????- ??????

• ?????DI (mg/kg-day)??????
• DI (Cw ? SA ? PC ? ET ? 10-3)/BW
•  
• ??
• Cw ???????,mg/L
• SA ??????,cm2
• PC ??????,cm/hr
• ET ?????,hr/day
• BW ??,kg

47
?????????????
48
????????-???????

• ?????DI (mg/kg-day)??????
• DI ( CS ? AF ? ABS ? SA ? 10-6 ) / BW
• ??
• Cs ????????,mg/kg
• AF Adherence factor,mg/cm2
• ABS Absorption factor (???)
• SA ??????,cm2/day
• BW ??,kg

49
??????

• ????(??????????),?????????CDI (chronic daily
  intake)???????
• ??
• C ???????????,mg/L or mg/kg
• CR ?????,L/day or kg/day
• EF ????,days/year
• ED ????,years
• BW ??,kg AT ????,days

50
???? (Risk Characterization)

• --???????????????????,????????????????????????

51
?????????

• ???????????
• ??????????,??????????,???????????
• ?????????????????????????
• ?????????????????????????

52
????

• ???????????????????????????????????????,???????
  ?
• ??????????????????,????? (margin of
  exposure)????????????????????????
• ??????,??????????????????????? (unit
  risk),?????????????,??????????????????

53
?????????? (I)

• ???????? (HI)
• ??
• I ????, (mg/(kg-day))
• RfD ????, (mg/(kg-day)

54
?????????? (II)
??????????
?? CDIi ?i???????????????,(mg/(kg-day)) RfDi
?i?????????????,(mg/(kg-day))
55
??????????(III)--?????

• ????? (total exposure hazard index, THI)
• ?????????????
• THI HI (pathway 1)HI (pathway 2).
• HI (pathway i)
•  
• ????????1,?????????????????????1,????????????
  ???

56
?????????Reference Doses (RfDs)
Reference Dose mg/kg/d
Acetone 0.1
Cadmium 0.0005
Chloroform 0.01
1,1-Dichloroethylene 0.09
Methylene chloride 0.06
Phenol 0.04
Toluene 0.3
Xylene 2.0
Adapted from US EPA IRIS.
57
??????? (I)

• ????(Risk) CDI SF
• ??
• CDI ???????? ,(mg/(kg-day))
• SF ??????,(mg/(kg-day))-1

58
??????? (II) --??????

• ???????????????????
• (?????10-6, ?????)?
• ??
• Riskt ??????????
• Riski ?i ?????????

59
?????????

• ?????????????,??????(Monte Carlo
  Analysis)?????????
• ??????????????,???????????????????,????????????(d
  istribution),??????????????????????????????????,??
  ???????????????????????

60
????????????

• ????????????????????,?????????????????????,???????
  ?????????????,????????????????
• ???????????????,???????????????????????

61
?????????

• ????????????
• ????????????????????????????????
• ??????????????????????????????????????????

62
??

• ???????????????????????????????
• ???????????????????,?????????????,??????????,?????
  ??,??????,????????????