Ch.4 ????? ???????

1
Ch.4 ????? ???????
2
???????

• ????, ????, ???? ? ?? ?? ??
• ??? ?????? ?? ?? ??? ???? ? ??? ??? ????? ????
  ??? ?? ??
• ?? ? 1,200? ??? ????
• ????? ?? 35,000??? ????? ??
• ????? ???
• ???? ???
• ???? ???
• ??? ??
• ???? ???? ?????(aflatoxin) ?
• ?? ??(basil)? ???? ?? ?????(estragole)
• ???? ???
• ???, ??? ???, ??, ???, ???, ?? ?
• ??? ???? ??, ??, ???? ????

3
???? ??? ???

• ????? ????, ?? ???, ?? ?? ? ?? ???? ??? ??? ?????
  ??? ??? ??? ??? ??? ??? ??
• ???? ?? ??? ???? ??? ?? ???? ???? ??
• ??, ???? ??? ??? ???? ?? ??? ???? ???? ??? ??
• ????? ?? ?? ??
• ?? ?? ??(Acute poisoning effects),
• ?? ?? ??(Chronic poisoning effects),
• ?(Cancer),
• ????(Mutations),
• ?? ??(Reproductive error) teratogen(??????,
  ?????))
• CMRs ????(Carcinogen), ??????(Mutagen),
  ??????(Reproduction toxicant)? ??? ??

4
Thalidomide
5
??? ??

• Risk assessment (?????)
• ???? ???? ????? ????? ? ??? ? ?? ??? ?? ?? ?????
  ???? ??
• Risk (???)
• ????? ?? ??, ?? ?? ????? ??? ??, ??, ???? ?? ???
  ??? ??? ??
• Hazard (???)
• ?? ??? ?? ?? ????? ???? ???? ???? ???? ??
• ???? ??
• ?? ???
• ??? ??? ??? ?? ????? ???
• ?) ???? ?? ?? ?? ??
• ??? ???
• ??? ??? ?? ??
• ?) ????? ??? ?? ??? ?? ??? ?? ?? ??
• ? ???
• ?? ??? ??? ???

6
????? ???? ??? ?
7
100??? 1? ???? ??? ??? ????? ??? ??
8
???????

• ?? ?????? ????? ???? ??? ? ?? ?? ?? ??? ?? ?????
  ???? ???? ??
• ?? ???(NAS, 1983) ??? ?? 4??
• ??? ?? (Hazard identification)
• ??-?? ?? (Dose-response assessment)
• ?? ?? (Exposure assessment)
• ??? ?? (Risk characterization)

9
(No Transcript)
10
??? ??? ??

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

11
??? ?? (Hazard identification)

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

???? ??? ?? ??? ?? ??? ??? ?? ??? ?? ???
???? ??(mg/kg-??) ?? ?? ??
1. ??? ??? 15,000 ?? 1?? ??
2. ?? ?? 5,000-15,000 1??-1??
3. ?? ?? ?? 500-5,000 1??-1??
4. ?? ?? 50-500 1???-1??
5. ?? ?? 5-50 7??-1???
6. ??? 5 ?? 7?? ??
12

• LD50 (Lethal Dose 50 ???)
• ??????
• ??? ??? ????? ???? ???? ????
• ????? ????? ? 50? ???? ??
• ??? ???? ??? ?? (But ?? ?? ?? ???)
• LC50 (Lethal Concentration 50)

13

• ??? ??? ?? ??
• Ames mutagenicity assay
• ?? ??? ???? (Short-term carcinogenesis bioassay)
• ?? ??? ???? (Chronic carcinogenesis bioassay)
• 2? ??? ???
• 50?? ??? ?/?
• ??? ? ?? 2?? ???
• ??? ?? ????

14
??? ????? ?? ???? ?? ?? (USEPA, 1986)

• ????, ????, ???? ?? ??? ??
• A? ??? ?? ???? (??? ????? ?? ??)
• B? ??? ???? ?? (Probable).
• B1 ???? ???? ?
• B2 ??? ?? ??? ????? ??? ??? ??? ??? ??? ??.
• C? ???? ?? ?? ?? ?? (Possible).
• ???? ??. ??? ???? ??? ?? ?? ??.
• D? ??? ?? ?? ? (not classified). ??? ??? ???
  ?????? ?? ??? ??? ?? ????.
• E? ?? ??? ?? ?. (??? ? ?? ??? ???? ??? ??? ??
  ????)

15
??-????

• ????? ??? ????? ????? ?????? ????? ??
• ???? ??(threshold)? ??
• ??? ??? ??.

16
?????? ??

• ?? ??? ??? ??? ??? ??? ???? ?? ???? ?????
  ???(??)? ??
• ??? ?? ?? ??? ?? (??? ? ??) ?? ??? ??? ??? ?? ?
  ?? ??
• ??
• ??EPA ?? ??? ??(?? ??? ??)
• ??? ?? ?? ? ??? 95? ??

??? ?? ???? ???
Probit/Lognormal (Mantel-Bryan) ???? ??? ????? ??? ???? ?? ?? ????. M-B ??? Probit??? ??? ß1? ????.
Multihit/one-hit ? ????? ?? ?????? ????? ??? ??? k?/1?? hit? ???? ??.
Weibull n?? ??? ???? ????, ? ???? ?? ??? ??? ?? ???.
Multistage ??? ????? ???? ???? ???(k??)? ???? ? ??? ??????.
17
????? (Non-Carcinogens)

• NOAEL(No-Observed-Adverse-Effect Level, ???????)
• LOAEL(Lowest-Observed-Adverse-Effect Level,
  ????????)
• RfD(Reference dose) ????? or ?? ??
• ????? ?? ??? (acceptable daily intake, ADI)
• ??? ???? ?? ?? ?? ?? ??.
• ??(CDI? ??) ?? ?? ???? mg/kg-day

18

• ???? ??(Uncertainty factor, UF)
• ???? ???(sensitivity) ??
• ???? ??? ??? ??? ??? ????
• ???? ????? ??? ??? ??
• ?????? ?? ?.
• ????(Modyfing factor, MF)
• ???? UF?? ?????? ????? ??? ??? ?? ?? ???? ?? ??.
  1? 10??? ?? ???? default value? 1? ?

19
? 1.21.3. ???? ??  
WHO WHO EPA EPA
? ? ? ? ? ? ? ?
??? ?? ??? ???? ?? ??????? ??? ??? ??? ??, ???? ????? ????? ???? 10 ????? ??? 1-10
??? ?? ??? ????? ??? ??? ????? ???? ????? ???? ???? ??? ???? 10 ????? ???? 1-10
??????? ????? ??? ?? ????? ??????? ???? 10 ????? ??? 1-10
NOAEL ?? LOAEL? ??? ??? ???? 10 ??? ?? 1-10
????(MF, modifying factor) ???? ??? ???? ???? ???? 10 -
? ???? ??? 10,000? ?? ???. ? ???? ??? 10,000? ?? ???. ? ???? ??? 10,000? ?? ???. ? ???? ??? 10,000? ?? ???.
WHO, The International Program on Chemical Safty
(IPCS) http//www.who.int/ipcs/en/
(3) ????
20
???? (Carcinogens)

• ???????(CDI, Chronic Daily Intake)
• CDI????(mg)/???(kg)??(day)
• ??? 70?? ??
• ????(?????)X(???)X(????)X(???)
• ????(Potency factor) ?????(Slope factor)
• ?? ??? ????? CDI X PF
• ???????(DWEL, Drinking Water Equivalent Level)
• 10-6? ???? ??? ??

21
????

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

22
(No Transcript)
23
Key Steps in Exposure Assessment

1. Identify significant pathways
2. Determine concentrations in environmental media
   that are contacted
3. Assign exposure factors
4. Calculate chemical intake

24
Identification of Significant Exposure Pathways
25
lt???-??? ??? ????? ??gt
26
Concentrations in Environmental Media that are
contacted

• Sampling and Analysis
• accurate quantification of dose
• expensive
• temporal limitations
• Mathematical Modeling
• greater uncertainty
• less expensive
• retrospective and predictive
• Behavior Analysis

27
3. Assign Exposure Factors

• Approaches based on either maximally exposed
  individual (MEI) or reasonably maximally exposed
  (RME) individual
• significant pathways
• how, when, where exposure occurs
• duration of exposure
• individual variations
• Standardized exposure factors available, e.g.
  Exposure Factors Handbook, EPA/600/8-89/043 and
  updates

28
Example Human Exposure Factors
Male Female
Lifespan (yr) 70 78
Body weight (kg) 70 60
Residential exposure period (hr/d, d/yr) 24, 365 24, 365
Occupational exposure period (hr/d, d/yr) 8, 250 8, 250
Food intake (wet g/day) 1500 1500
Water intake (mL/day) 2000 2000
Air intake (m3/day) 20 20
29
4. Calculate Chemical Intake
Example Ingestion of drinking water
30
??? ??

• ??????? ??
• ?? ??? (Margin of Exposure, MOE)
• ??? ?? (Hazard Index, HI)
• RSC(Relative source contribution)
• ??? ???
• ???-20, ???-10
• ????? ??
• CDI X PF

31
?? ???

• ??? ???? ??? ??
• ????? ??
• ? ????? ?? ??? ???? ???
• ?????? ??
• ? ??? ?? ?? ??? ??? ?? ???
• ? ??? ??? 1 ??? ?? ????
• ???? ??? synergy ?? ???

32
??? ???? ??
???????(individual lifetime risk) ??(dose) ?????(potency)
???????(population risk) ??????? ?????(population exposed)
?????(relative risk) ?????? ???(incidence rate in exposed group) /??????? ???(incidence rate in nonexposed group)
??????(standardized mortality or morbidity ratio) ???? ???(mortality in exposed group) / ??????? ???(mortality in general population)
????? ??(loss life of expectancy) ??????? 36?(avg. remaining lifetime)
33
??1

• ????? ?? ????? ?????? ???????? ??-???? ???? ??
  ?????? ??? ???.
• ? ?? ???? ??? ??? ??, ????? ???? ??
  chloroform(CHCl3)? ????. (????
  6.1103(mg/kg/day)-1)
• ?? 70kg? ??? 0.1mg/l ??? chloroform? ?? ?? ?? ???
  2l? ??(70? ??)?? ?? ??? ???? ?? ??? ????.

34

• 1. ?? ??? ?? ?? chloroform?? ??? ??? ?? ?? ??????
  ???? ???? ???? ????.
• CDI1??????/??0.1(mg/l) X 2(l/day)/70(kg)0.00286
  
• ???CDI X PF(SF) 0.00286 6.1 10-317.4 10-6
• 2. ?? ? ??? 500,000?? ? ?? ???? ???, ??? ? ??
  chloroform?? ?? ?? ?? ??? ??????
• 500,00017.410-670 0.12 ?/?
• 3. ???? ??? chloroform? ?? ??? ?? ? ??? ?? ??? ??
  ?? ???? ????(???? ?? ?? ???? ?? 100,000 ?? 193???
  ????.).
• 1935 965 ?/?
• ??? ?????? ?? 0.12?? ??? ? ?? ??

35
??2

• ??? 60kg? ???? ??? ?? ???? ?? ????? ????? ? ?
  ???? ????.
• ????? 20?, 1?? 50?, 1?? 5?? ????. ???? ?? ?? ?
  2??? 1.5m3/??? ??? ??? ??? ?? ? ? 6??? ?????
  1m3/??? ??? ??? ??.
• ????? ????? 0.02(mg/kg/?)-1?? ???? 80? ????
  ????? ??? ?? ??? 0.05mg/m3?? ????.

36
??3

• ?? ?? ??? ???? ???? ????? ?? ?? ?? ??? 0.3mg/l ??
  ????? ?? 10cm ? ??? 1km ??? ??? ???? ??. ????? 1?
  ???? ???? ???? 10???.
• ???? ???? ???? ????
• ???? ??? ??? ??1000m100/1010000?
• ???????

37

• ???? ????? 0.02(mg/kg-day)-1? ? ??? 70kg ? ??? ?
  ?? 10?? ?? 2??? ?? ?? ???? ??? ???? ????.
• ??? ???????(DWEL) ?? ?? ???? ??? ????? ???? ??.

38
??? ??? ????

• ??? ????
• ?????? ???? ??
• ???? ??
• ??? ??, ?????? (I)? ????
• ??-?? ????
• ????? ??? ???? ??? ? ? ??? ???? ??
• ?????? ???? ???? ???? ????
• ?? ?? ?? ???? ??? ?? ??? ??
• ??? ????? ?? ???? (??? ????)
• ??? ????? ??(extrapolation)?? ??? ?? ??
• ???? ????? ??? ???? ??? ?? ?? ??? ??? ???? ???
  ??
• ??? ????
• ?? ???
• ????? ??? ?? ??? ??

39

• ??? ??? ????? ?? ??
• ??? ????? ?? ??? ??
• ?? ??
• ?? ???
• ????? ?? ???? ?
• I, SF, RfD ?? ?? ?? ?? ????? ?? (Monte Carlo
  Simulation ?)
• ???? ?? ???? ?? ??

40
???? ?? ????

• ?? ??? ??? ?
• ?? EPA??
• ??? (10-4 - 10-6)
• ???? (???? 1 ??)
• ????? ??? ????? ???? ????? ?? ?? ??
• ?????? ??? ????? ???? 1 ????? ??
• ???? ??
• ??? ??? ??? ??? ?? (???, ??? ??)
• ???? ??? ??? ??? ??? ???/???, ???/?? ?, ???/
  ???, ???/???
• ??? ??? ??? ????? ???? ?? (???? ??? ???? ????)
• ???? ??? ???? ?? ??? ???? ??? ?????

41

• ???? ?? ????
• ???? ?? ???? ???? ???? ?? ????? ?? ??? ?? ?? ????
  ?? ???? ?? ??? ???.
• ??? ?? ????? ???, ???, ??? ?? ?? ??? ??? ??? ????
  ??
• ???? ???? ? ?? ??? ????? ???? ????? ??
• ?? ????(??)
• ????/????(???, ????)
• ????/????(??)
• ??????(???)
• ??????(??)
• Solution ?
• To the best of the knowledge ???, ??? ??? ???
  ??? ????
• ???, ????? ??? ????? ?? ???? ??? ??? ??? ??,
  ????? ?????? ??? ?? ??

42
????? ??? ??

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

43
????? ?????? ????
????? ?? ? ?? ? ??
???

• ??,??, ??
• ????

• ??????
• ??? ???

?? ? ?? ??
??? ???
??? ??

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

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

• ????? ?? ???? ??
• ???? ??

44
??? ??? ?? ???

• ?????? ???
• 2005. 12. 30 ??
•  ???? 7? 4? ??1?? ??? ?? ?????? ??? ??, ?????
  ???? ? ?? ??? ??? ????????? ????.
• ????? ????? ?? ?? ?? (????????? ?2005-19?
• http//newchem.nier.go.kr
• ??2? ???????? ????(2006-2010)???? ??, ??, ?? ?
  ??? ????? ?????? ????? ??? ????? ????? ???? ???

45
???? ??? ????
?1?. ????? ???? ?4?. ???? ????
?1?. ??????   ?1?. ????????  ?2?. ????????  ?3?. ????????  ?4?. ?? ????? ? ?????  ?5?. ?? ???? ? ?????  ?6?. ???????  ?7?. ??????  ?8?. ???????  ?9?. ??????  ?10?. ??????  ?11?. ??? ? ??? ????  ?12?. ??????  ?13?. ?????  ?14?. ????????(?????)  ?15?. ????????(?????)
?2?. ???? ????   ?1?. ????????  ?2?. ????????  ?3?. ????????  ?4?. ?? ????? ? ?????  ?5?. ?? ???? ? ?????  ?6?. ???????  ?7?. ??????  ?8?. ???????  ?9?. ??????  ?10?. ??????  ?11?. ??? ? ??? ????  ?12?. ??????  ?13?. ?????  ?14?. ????????(?????)  ?15?. ????????(?????)
  ?1?. ????????  ?2?. ???? ??????  ?3?. ?? ??????  ?4?. ??? ??????  ?5?. ???? ????  ?6?. ?? ??????????  ?7?. ???? ?????   ?1?. ????????  ?2?. ????????  ?3?. ????????  ?4?. ?? ????? ? ?????  ?5?. ?? ???? ? ?????  ?6?. ???????  ?7?. ??????  ?8?. ???????  ?9?. ??????  ?10?. ??????  ?11?. ??? ? ??? ????  ?12?. ??????  ?13?. ?????  ?14?. ????????(?????)  ?15?. ????????(?????)
?3?. ????? ? ????? ????   ?1?. ????????  ?2?. ????????  ?3?. ????????  ?4?. ?? ????? ? ?????  ?5?. ?? ???? ? ?????  ?6?. ???????  ?7?. ??????  ?8?. ???????  ?9?. ??????  ?10?. ??????  ?11?. ??? ? ??? ????  ?12?. ??????  ?13?. ?????  ?14?. ????????(?????)  ?15?. ????????(?????)
  ?1?. ???????  ?2?. ???????   ?1?. ????????  ?2?. ????????  ?3?. ????????  ?4?. ?? ????? ? ?????  ?5?. ?? ???? ? ?????  ?6?. ???????  ?7?. ??????  ?8?. ???????  ?9?. ??????  ?10?. ??????  ?11?. ??? ? ??? ????  ?12?. ??????  ?13?. ?????  ?14?. ????????(?????)  ?15?. ????????(?????)
46

• Dr. Bruce Ames, known for his work in the
  development of short-term mutagenicity tests,
  gave a seminar on the Davis Campus on March 1,
  1986. I wrote the following article based on
  notes I took during the seminar. This article was
  edited by Dr. Ames and he added some information
  I had missed during his seminar
• Based on this index, a glass of chlorinated tap
  water has an index (based on it's content of
  chloroform, a trihalomethane) of about 0.3. A
  glass of well water contaminated with
  trichloroethylene at about 3 ppm (the worst well
  in Silicon Valley), had an index of about 1
  mainly due to the fact that TCE is substantially
  weaker than chloroform as a carcinogen.
• He stated "I'm just very skeptical of water being
  a serious contender for any kind of carcinogenic
  risk".
• Eating grains containing EDB had an index of
  about 0.4, about equivalent to a glass of
  chlorinated tap water. A few strips of bacon
  (nitrosamines) had an index of 9, and a peanut
  butter sandwich (aflatoxins at average 2 ppb) an
  index of 28. (FDA allows 10x this.)
• Dr. Ames also had good news for the beer drinkers
  of the world. Ethyl alcohol (in its various
  forms) is considered a human carcinogen of the
  liver, mouth and esophagus. It has recently been
  shown to cause cancer in rats which would give a
  daily bottle of beer on the scale an index of
  2700 based on the rat data.
• WATER, Vol. 27, Number 2 (Summer 1986).
• Arthur L. Craigmill Toxicology Specialist, U.C.
  Davis

47

• Thus, according to the HERP index (Human Exposure
  Rodent Potency),
• consuming one gram a day of dried basil (that's
  one twenty-eighth of an ounce) or
• eating one raw mushroom a day is 100 times more
  hazardous than
• drinking a quart of chlorinated water every day
• and 25 times more hazardous than drinking the
  most contaminated well water in the Silicon
  Valley in California.
• HERP (Human Exposure Rodent Potency) index ???
  ???? 1? ?? ???? ? ????? ??? ?? 1/2? ?? ???? ????
  ? ??? ?
• New York Times
• May 6, 1987
• PERSONAL HEALTH By JANE E. BRODY

48

• Ames? ?? ???? '?? ????? ???? ?? ??? ????? ???
  ???? ?? ??? ????? ???? 100? ?? 1,000?? ? ?? ????
  ?? ??? ????? ???? ??' ? ??. ??? ???? ??, ???, ???
  ????? ???? ?? ????? ????? ??. ??? ???? ????? ??,
  ??? ?? ????? ???? ?? ??? ?????? ???, ????? ????
  ?? ??? ???? ?? ??? ????. ??? ????? ???
  ??????(EDB)? ???? ?? ???? ??? ??? ????? ???? ??
  ??? ? ??? ???? ?????? ??? ??? ??. Ames? ??? ???
  ?? ? ?? ???? ??? ?? ??EDB? ???? ?? ??? 10,000?? ?
  ?? ?? ?? ???? ??? Rachel Carson? ???? ??? ????
  DDT? ???? 1.000?? ???? ??? ??. ??(basil)? ? ?,
  ??? ? ???? ?? ?? ? ?? ? ???? ??? ??? ??? ??? EDB?
  DDT ???? 100???1,000?? ?? ?? ???? ??? ??? ??.

?? ??? ??(????)
0.0003 DDT, ?? ???
0.0004 EDB, ???? ?
0.001 ??? ???? 48???? 1?(?????)
0.03 ???? ???? 1?(?????)
0.03 ???? 1?(Symphytine)
0.07 ???? 1???(?? ??????)
0.1 ???? 1?(?????)
0.1 ???? 1?(????)
2.8 ?? 12???? 1?(????)
4.7 ??? 8???? 1?(????)
49

• ?? "?? ??? ??? ???? ??"  2007-10-12 1138 ???
  ?? ?? ? ?? ??? ????? ?? ????? ????? ???? ???
  ??????.???? ??? ???, ????? ???? ?? ?? ?? ???
  ??? ??, ??? ??? ?? 75??? 1??? ?? 109.4 ??????? ??
  ?????? ????? ?????.?? ??? ????, ??? ??? ??? ??
  ?? ?????? ? ?? ????? ?? ??? ?? ?? ???? ?? ?? ???
  ??? ? ? ??? ??????.(??? ???)

50

• Arsenic Blackfoot syndrome