CARCINOGENIC RISK ASSESSMENTS




                               OF




                POLYCHLORINATED  BIPHENYLS  (PCBs)
Executive Summary
     This document  presents the HERD risk assessment for



carcinogenicity of  PCBs  and summarizes the results of four



previous PCS risk assessments for cancer conducted by FDA,  OTA,



and CAG/SPA, and OTS.   (Unfortunately, no consolidated



assessment can be developed from these sources, because of  the



different units and different techniques used.  However,  the



results from these  various  risk assessments are consistent,



though not directly comparable).







     In light of these  earlier assessments we chose studies by



NCI (three positive dose  levels)  and  Kimbrough  (one pusitive



dose level), respectively,  from which to extrapolate



carcinogenic risks  at low exposures.   The NCI study has  been



criticized by other authors as having too few animals in each



sex-dose group;  nowever,  the  study  was used because no



consistent differences  or trends  in responses by sex were found

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and with pooled data  for  males  and  females it allows the best
characterization of dose-response,  unlike  the Kimbrough study
with only one dose  level.   Cur  results  are within a factor of
three of the  FDA risk assessment  of  carcinogenicity of PCS,
which used both Kimbrough's  data  and the  NCI data.

     Estimates of human exposure  come  from the Exposure
Evaluation Division of  OTS.   Other  relevant features of the
risk assessment are :  1)  The  extrapolation distance between the
lowest experimental dose  (1.25  rag/kg/day)  in the NCI study and
many of the exposure  estimates  can  be  very large.  The larger
the distance  the less confidence  one might have in the
assessment.   2) The dose-response data  for total malignanciess
nre also linear, this corresponds well  with the "linearized"
upper 95% confidence  limits  from' the GAG model.

     For regulatory purposes  and  for the purposes of comparing
risks of PCBs with  those  for  other  chemicals,  it is suggested
that the number from  the  95%  upper  confidence bound found in
the multistage model  in that  table  be  used.  This model is
routinely used by CAG to  set  air  and water quality criteria and
standards.  The. estimates of  exposure  for  which carcinogenic
risks are calculated  are  based  on conservative assumptions.
Few, if any,  individuals  will be  exposed to these relatively
large amounts, of PCBs.  The  carcinogenic risks calculated for

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typical members  of  exposed groups are believed  to  be  no  higher



and probably much  lower  than those presented in  this  document.








Previous Quantitative  cancer Risk Assessment








     This memorandum  summarizes and pulls together  for the



first time the information available from previous  quantitative



risk assessments of  PCBs,  and updates and fills  in  gaps  in  that



area.  It concludes  with  on an HERD risk assessment of PCBs.








     The first risk  assessment to be summarized  is  that



conducted by the EPA  Carcinogen Assessment Group (CAG) for  the



Office of Water  Regulations and Standards, Criteria and



Standards Division  (EPA,  1980) .  This risk assessment was used



to set an ambient water quality criteria level as shown  in



Table 1.  (CAG Table page  C-84).   In Table 1 are the estimated-



concentrations of PCBs  (or virtually safe doses) corresponding



to lifetime cancer  risk levels  of 10"~7,  10"^,  and 10~5.  These



concentrations are,  as  CAG said,  "exceedingly low."  The cancer



risk levels stand for additional  incidence of  cancer in an



exposed population.   CAG  used the "linearized"  multistage model



( Crump,  1931)  which  is linear at  low doses or  exposures so  that



the additional lifetime risk is directly proportional to PCB



intake.   CAG's risk assessment  considered only  the



bioaccumulation of  PCBs in fish and  shellfish,  plus exposure

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through drinking water.   Exposures  from other food sources,
air, or occupational exposures  were  not included in the
criteria level derived  by  GAG  using  Crump's  model.

     For experimental data,  CAG  chose  the  study by Kimbrough et
al. (1975)  of Sherman rats,  although CAG indicated that rats
appear to be much less  sensitive  to  the acute and subacute
effects of PCBs than man or  non-human  primates.  In 184 rats
treated with 100 ppm PCS in  their diet,  Kimbrough observed 26
hepatocellular carcinomas  compared  to  1/173  hepatocullar
carcinomas in controls.   CAG considered all  of the mouse
studies of PCBs unsuitable for  a  quantitative risk assessment
of cancer because none  of  them  involved feeding for most or all
of an animal lifetime.  They also criticized the NCI study of
PCBs (NCI,  1978), the only other  long-term major study of PCB
exposure that suggested a  carcinogenic effect, as using too few
experimental animals to establish a  basis  for assessming
carcinogenic risk.

     Crump conducted the  PCB risk assessment (conversation with
Qiao Chen,  November 18, 1982) but documentation of some details
is incomplete.  He combined  the Kimbrough  animal data for
hepatocellular carcinoma and liver  neoplastic nodules, the two
tumor types observed in the Kimbrough  study.  At control the
proportion responding was  1/173,  but at the  high dose the
proportion responding was  170/184.   Crump  assumed that the

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average  weight  of  a test rat was 400 grams  resulting  in a



conversion  from 100 ppm to 4.42 mg/kg/day.   ( CAG  normally



assumes  rats  weigh 350 grams).







     The  formula  for calculating VSD's for  humans  is  then
     VSD  = 70
           q2 x  (2  +  CT. OOb^kg x 46,000)
where 2  is  a daily  consumption of 2 liters of drinking  water,



6. 5g is  an  assumed  daily consumption of fish and shellfish,



46,000 is the  bioconcentration factor (because of  the size  of



this factor all of  risk  comes from comsumption of  fish  and



shellfish,  not water),  10"^ is the presumed acceptable  lifetime



risk, and 70kg is.the weight of a human.  The above formula



appears  on  p.353  of the  Friday, November 28, 1980,  Federal



Register EPA Water  Quality Criteria Document;  Availability



(L'.S. EPA 1980),  and q2  is the potency calculated  from  Crump's



model using 1/173 at 0 mg/kg/day and 170/184 at 4.42



n;g/kg/day.  Thus, q2 for rats = .69 and qi. for humans is



achieved by multiplying  by a species conversion of  5.85.  This



gives 4.01.  Thus.  VSD = 5.8 x 10~7 mg/1 or 0.58ng/l.   This  is



close to .79ng/l, the value derived by CAG for 10~5 risj< in



(Table 1).  The small difference between CAGs risk  assessment

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and our reconstruction  of  it is unexplained, perhaps  Crump  made
an adjustment for  the number of days  in the experiment  (730)
versus the numer of  days  the animals  were exposed (645) .

     CAG noted several  drawbacks of  the Kinbrough study.  Since
it had o.nly one dose  level  it could  not provide any evidence  of
the shape of the -dose-response  curve  and it tested one  species,
one sex, and only  one commercial mixture of PCBs.  CAG  added
that Kimbrough's experimental design  was good in that the
dosing was for a large  proportion of  the liftapan of  the
animals, the food  route was  appropriate, and the dose over  time
was uniform.  Also,  there  was good documentation of the intake
dose, a sufficient number of test animals were used for
statistical tests  of  increases  in tumors, and a thorough
description of the pathology was provided.  Finally,   CAG noted
that an "acceptable  no  carcinogenic  level" could be established
with greater certainty .if  better quantitative data on
c^arcinogenicity had  been available.   They also felt that
studies with larger  numbers  of  animals  designed to measure
relatively small effects were needed.

     The second risk assessment to be  summarized is  that
conducted by the PCB Risk  Assessment  Work Force of the  Food and
Drug Administration  ( Cordell et al.,  1982).   This group used
both the Kimbrough (1975)  data  and the  NCI (1978)  data  to
estimate carcinogenic risk  to humans  from consumption of fish

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contaminated  with PCBs.   FDA used linear extrapolation  from



high doses  in  the animal studies to the lower exposures  of



consumers  of  PCB contaminated fish and water.   Linear



extrapolation  was defended  by the authors on the grounds  that



one cannot  deduce or directly observe the shape of  the  low end



of the dose  response curve  with precision, and  among the



available  methods,  linear extrapolation from high  to low  doses



appears  to  be  consistent with what is known about  the



biological  mechanisms  of carcinogenesis as well as  least  likely



to underestimate cancer  risk.  They also point  out  that  linear



extrapolation  as used  by Qrump is the limiting  case  (upper



confidence  limit on  risic) on his multistage model at low



doses.   Hence,  "linearized"  multistage model (Crump, 1981).



"Instead  of  using the entire  Crump's model, however, the authors



placed 99%" upper confidence  bounds on the animal response..data



to control, fdr.the  effect of sample size so. that they could



make comparisons between experiments.  Use of upper bounds  on



risk along  with  linear extrapolation involved an additional



degree of  conservatism in  their risk assessment.







     An  additional  element of uncertainty was brought out by



the FDA  that was not considered in the CAG assessment.   That



is, there  is an  absence  of  toxicity data on the  particular set



of PCBs  that occur  as  residues in fish.   Due to environmental



transformation,  the  chemical composition of PCB residues  found



in fish  differs  from that of industrial  PCB products (e.g.,

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ArocLor 1254 and  1260) ,  although a typical PC3 residue  in  fish



resembles the Aroclor  1254  mixture more  closely that it does



the other Aroclors.   For this  reason it  was uncertain that  the



available tqxicity data  from Kimbrough and MCI represented  the



toxicity of the PC3 mixture ingested by  humans who consume



fish.







     FDA's upper  confidence limits, on risk were thus computed



from the NCI Aroclor  1254  Fisher 344 rat  data, for both sexes



combined, on total malignancies  and liver carcinomas plus



adenomas.  These  data  are  shown  in Table  2 (FDA Table 5).



However, estimated risks from  the one sex Sherman rat data  on



Aroclor 1260 from the  Kimbrough  study were also computed.



Because the relative  susceptibilities of  humans and



experimental animals  to  the carcinogenic  effects of PCBs were



not known, FDA noted .that  the  risk estimates could obviously



severely over-estimate or  under-estimate  human risks.  The  FDA



risk estimates from the  NCI and  Kimbrough data, however,



demonstrated remarkable  agreement showing that the various  rat



strains used reacted  similarly  to PCS carcinogenic insult.



These risks are presented  as rates per 100,000 in Table 3 (FDA



Table 6) for various  tolerances  or "acceptable: d'aily intakes"



of PCBs and percentiles  of  fish-eating populations.  Exposures



in ng/1 or ppb are not directly  given.   Therefore it is



difficult to compare  the result  of this  risk assessment with



that of CAG's (already discussed)  or that of OTA's (to be

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discussed).   Table  4 (FDA Table 7) was derived  by  assuming that



the carcinogenic  risk  is  evenly distributed over a  70-year


period and  by multiplication of the size of the  fish-eating



population  at risk  times  the risk estimates shown  in  Table 2.



FDA also  noted that our Table 3 (from their Table  6)  may


underestimate- risks to  neonates who receive PCBs in mother's



milk, but who also  continue to consume food contaminated  with



PCBs after  childhood and  throughout their lives.






     The  third risk assessment uo be summarized was prepared



for the U.S.  Congressional  Office of Technology Assessment by


Kenneth Crump,  who  was  involved in the first risk assessment



discussed here  ( Crump and  Masterman,  1979).  Crump selected


three data  sets  to  use  in  his computation of virtually  safe



doses by extrapolation  of  the results of- animal experiments to


low dose levels.  These', data sets are shown in Table  5  (OTA



Table 11).  Crump's  rationale for selection of data sets  as  the


basis for risk  extrapolation was as follows.'  First,  Crump



agreed with CAG in  not  using the NCI  1978 study was not used



because it  involved  relatively few animals (only 24 per dose



group, whereas  the  usual NCI bioassay uses 50  (NCI, 1978)).


Second,  the Kimbrough study  was used because it provided  the



most convincing evidence of  the carcinogenicity of  PCBs


(Kimbrough  et  al.,  1975).   The study  involved  a relatively
                 x

large number  of animals and  the increased incidence of



hepatocellular  carcinomas  in the treated  group was  highly

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 significant.   This study was used with two endpoints,



 hepatocellular carcinomas and liver neoplastic  nodules.   Third,



 Crump used the Industrial Biotest study  (Industrial  Biotest



 Laboratories,  1971 from an unpublished report.   Reasons  for



 this  choice are not clear (Some of the data  from this  testing



.company  have  been found to be fradulent).  The  slides  from this



 "study were examined at least .twice, with markedly  different



 results.   Even so,.the rediagnosis of the liver  pathology had



 indicated a significant tumorigenic effect.  There was also



 unusually high mortality and interim sacrifices  further  reduced



 the numbers of animals on test.







      He  then  selected several high-to-low dose  extrapolation



 procedures:  the probit moilel (Mantel, et al. ,  1975),  the one-



 stage or  one-hit model (Crump et al..,  1977)  and  the multistage



 model (Crump,  1981).   The gamma multihit model  (Rai and  Van



 Ryzin,  1978)  was also considered but could not be  used :   it



 requires  data with at least two positive experimental  doses and



 thus  could not be applied to either of the Kimbrough and



 datasets, and when the computer algorithm for computing  the



 estimates failed to converge for the third data  set (Industrial



 Biotest) .







      Table 6  (OTA Table 12)  presents the computed  maximum



 likelihood estimates  in ppb of the lifetime dose required to



 produce  additional risks over background of 10"^,  10"^,  and





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10"5.   Recall  that GAG considered risk levels  of  10~7,  10~6,
and  10"5  for  its  virtually safe doses (Table 1).   Lower  95%
confidence  bounds for each of these virtually  safe  doses were
also computed  from various models.  Likewise,  as mentioned
earlier,  the gamma multihit model was applied  only  to  the third
data set  since  this  model could not be applied to data
containing  only one  experimental dose."  In the case  of one
experimental dose,  however,  the one-hit model  and multistage
model produced  identical results.

     Crump  believed  that the Kimbrough study provided  the most
convincing  evidence  of the carcinpgenicity of  PCBs,  he used
these data  to calculate  risks for estimated PCS exposures.  The
fact that only one  dose  level of PCB was tested in  the
Kimbrough study meant  that the .one-hit model was the -only one
that could  be utilized.   "Crump then, converted  PCB exposure
levels  from the the  FDA  Total Diet Study (Johnson and Marshe,
1977) to equivalent  exposures in rats.  The FDA Total  Diet
Study exposure levels  come from a market  basket of food
(representing the  basic  2-week diet of a 16-to-19 year old
male) which was collected in each of several geographic
areas.  The various  foods were prepared in the  manner in which
they could  normally  be eaten and were  then analyzed  for  the
presence of various  substances,  including  PCBs.  The estimates
of dose from this  study  were felt to be  tenuous,  however.
Exposures to PCBs  in  Michigan sport fish  came from a 2-year

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(1973-1974) study made  under an FDA contract (Humphrey,  1977)
of persons who regularly  consumed  PCB-contaminated Lake
Michigan sport fish  and  randomly selected persons who did  not
consume such fish (Humphrey,  1977).

     Crump's then fitted  a  one-st.jp model to the animal  data  to
estimate the extra risk of  hepatocellular carcinomas at  this
dose.  Crump did not mention allowing for any difference
between the composition of  PCBs in  food  to which humans  are
exposed being and the composition  of Aroclor 1260 used in  the
experiment.  But, neither  CAG nor  FDA considered the difference
between the types of PCBs  in fish  and Aroclor 1254 and 1260.
Crump did comment that  PCB  levels  in human adipose tissue  are
likely to.be much greater  than corresponding levels in rats for
a given level of dietary  exposure,  but this also was not used
in the risk estimates.  ..The estimates are given in Table 7  (OTA
Table 13).  Upper confidence  bounds  on these risks are not
listed, but could as the  author said that they could be
obtained by multiplying all corresponding risks by 1.5.

     From the estimates, in  Table 7  Crump computed that
nationwide exposure at  the  dietary  level detected in the 1976
Total Diet Study (3.3 ug/day to 8.7  ug/day)  ould cause  4.1 to
11.1 extra hepatocellular carcinomas in  the U.S.  Crump  also
used the one-hit model  with estimates of PCB levels in Lake
Michigan fish, to find  an average  excess of 0.22 hepatocellular

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carcinomas  among  residents of Michigan Cbunty exposed  to PCBs

in Lake Michigan.   Crump did not indicate hepatocellular

carcinomas  in  rats  might translate into cancer at  other  sites

in man.   Crump  went on to estimate the risk of hepatocellular

carcinoma  in breast-fed infants and concluded that  the risk

could be at much  higher than for the U.S. population in

general.                        .



     Comparison of  results from the FDA, OTA, and  CAG risk

assessment  is difficult due  to the different units  in which

risk is expressed  in each assessment and the paucity of

explanation in  each risk assessment of some crucial assumptions

that may have been  made in each risk assessment.  Table  8

presents the extra  lifetime  risks  of cancer associated with

consumption of  PCBs in food  calculated by FDA and OTA in their

separate risk assessments.  CAG1s risk  assessment is not

compared here as  they presented their data only in  terms of

virtually safe  dose (Table  1).   Differences are readily seen.

These are primarily due to the different assumptions made in

the amount of PCBs  that would  be ingested and in the size of

the exposed population.   FDA's  risk assessment applies to the

15% of  the total  U.S.  population expected to consume the  fish

species known to be the most highly contaminated with PCBs.

The OTA calculations  are  based  on  FDA's  Total Diet Study  (3.3

and 8.7 ug/day) and on estimates of the  PCB intake of people
           /
who consumed more than 24  Ibs.  of  Lake Michigan sport fish per

year.
                               13

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     CAG and OTA both used  the  Kimbrough  experimental data.
However, CAG used conversions  for  exposure  concentrations due
to bioaccumulation  levels  in  aquatic  organisms which OTA did
not use.  All three risk assessments  are  in general poorly
documented and justified.   It  is  not  always clear whether
estimated virtually safe doses  or  increases in risk app:.y to
for animals or humans.   None  of the  three published risk
assessments explicitly refers  to  species-to-species conversions
(or any other conversions)  applied to either the exposure
estimates or the risks from the model.  Though we learned from
personal communication that CAG did  use species-to-species
conversions.

     F~)A used linear extrapolation while  OTA (Crump)  used the
one-hit model, but  this  difference,  is not  great because the
one-hit model is nearly  linear  at"low doses.   Another
difference is that  FDA used the NCI  study on  Aroclor 1254 and
while OTA used the  Kimbrough  study on Aroclor 1260.  Not only
were the number of  dose  levels  different,  but the responses and
tumor types were different.   Finally,  CAG,  FDA,  and OTA
probably used different  exposure  assumptions  about the
bioaccumulation or  biocohcentration  levels  in aquatic
organisms.  It is at least  known  that  CAG used a
bioconcentration factor  of  46,000.
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 HERD  Risk  Assessment




      We  now  updated and expanded the quantitative risk


 assessments  conducted  by CAG,  FDA,  and OTA.  Oncologists  from


 the HERD Oncology  Branch reviewed the NCI report "Bioassay of


 Aroclor  1254  for Possible  Carcinogenicity" and extracted  the


 detailed tumor  data presented  in' TabLe 9.  Categories for


 leukemias, malignant  lymphomas,  liver carcinomas, stomach


 adenocarcinoma  and gastrointestinal tract malignancies, and all


 malignant  tumors combined  were  established.  The data are


 presented  for males,  females,  and sexes combined.




      The categories of  stomach  adenocarcinoma and


gastrointestinal tract  malignancies ha/e an additional combined
                    "*
 subcategory, labelled "Morgan,  et al.".   Morgan et  al.,  1981


 reviewed the specimen's  of  the  stomachs of the Fischer 344 rats


 in the MCI study of PCBs and found  an incidence of   '


adenocarcinoma  of the glandular  stomach of 0/47,  1/48, 3/48 and


 2/48.   The "Morgan, et  al." subcategory  for stomach


adenocarcinoma  includes the tumors  in the combined  subcategory


because Morgan  included  but did  not  review the  adenocarcinomas


of the glandular stomach already  noted by NCI scientists.   The


Morgan, et al." s-ubcategory for gastrointestinal  malignancies


 is also a summation of  the combined  subcategory alone and  the


Morgan, et al. data.
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     The tumor categories  in Table 9 correspond with  the
categories in Table  2  (used  by  FDA for animal data in risk
extrapolation to humans) except that FDA combined liver
adenomas with carcinomas,  and  leukemias with malignant
lymphomas labelled hematopoietic neoplasms by FDA).   Liver
adenomas are frequently  defined to be benign.  (Personal
conversation with scientists in the Oncology Branch).  Note
also that a summation  of all the tumor categories in  Table 9
beginning with leukemias would  not be expected to add to'the
category of any malignancy.   This  is because any animal may
have had more than one type  of  tumor.  Thus, perhaps  any
malignancy would best  be called "at least  one malignancy."
Also, not all the tumor  types  observed in  the NCI study are
listed in Table 9, only  those  that were malignant.

     In parentheses  after  some  of  the tumor incidences in Table
9 are p-values derived using the Fisher Exact Test (Cox,
1970) .  In the cases where more than one Fisher Exact Test p-
value has been calculated  in a  given row,  a simultaneous
comparison using the same  control  group has taken place and the
Bonferroni inequality  was  used  to  maintain a significance of
p =  .05.  This occurs  for  the  following reason.   When results
for a number of treated  groups  are compared simultaneously with
those for a control  group, a correction is usually employed to
ensure the overall significance level that one has chosen.  The
Bonferroni inequality  requires  that for k  treated groups the p-

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value  for  such  simultaneous comparisons be less  than or  equal
to p-value/k.   In  the  case  of Table 9 a p-value or a-level of
0.05 was chosen.   The  only  dose levels or categories which were
statistically significant at a = 0.05 were the combined  data by
sex at  100 ppm  in  feed (or  5.00 mg/kg/day) for any malignancy.

     NCI's 'report  on  their  PCS; bioassay ( NCE, 1978) states on
pp. 25-26,

           "It is concluded  that under the conditions
          of this  bioassay,  Aroclor 1254 was  not
          carcinogenic in Fischer 344 rats;  however
          a high incidence  of hepatocellular
          pro-1 iterative  lesions, [hyperplastic
          nodules, adenomas,  and  carcinomas]
          in both  male and  female rats was related
          to treatment.   In  addition, the  carcinomas
          of the gastrointestinal tract may  be
          associated with tre'atment in both males
          and females  [none  of these lesions  were
          found in control  animals  in this study."]

     NCI did not establish  a category of "any malignancy' ;
therefore they did not conduct any  test  of statistical
significance for such  a  category.   However, as shown in Table 9
the p-value for the statistical  significance  of  the  21/48

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animals with any malignancy  at 5 mg/kg/day compared with  9/48

animals in control was  highly  significant at 0.0074.  The data

for female rats at 1.25 mg/kg/day were also significant;  it  is

not clear whether this  is  a  statistical aberration, as none  of

the higher doses was  significant.




     Leukemias and malignant  lymphomas are an. important tumor  

category in this study.   66.1  percent (41/62)  of the animals

with any malignancy had  one  of these  tumor types.  However,

this category  is difficult to  study  because of the high

background incidence  of  these  malignancies in  Fisher 344

rats.  Historically (up to 1979,  at  least), 6.5 percent of the

male rats and  5.4 percent  of  the  females  have  had spontaneous

occurrences of leukemias  or  lymphomas (Gart et al., 1979)  .

Similar rates  in the  1978  NCI  bioassay were 20.0 (19/96)

percent in male's, and  23.0 percent in females.  The-se
                                                 *

differences suggest that  the  significant  trend observed in the

NCI* study reflected a  real increase,  but  additional work would

be needed to settle the matter.




     Two additional tests  were conducted  of the data at each

subcategory, males, females, and  combined sexes.  The technique

used to derive both tests  comes  from  Armitage  (1955).  The

first test is a test  for  departure from linear trend.  If  the

p-value for departure  from linear trend is small, then the null

hypothesis of  linearity  (whether  the  association between dose



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 and  response  is a linear one) is rejected and one  concludes
 that  dose  affects cancer incidence but in a manner more
 complete  than linear.   Otherwise/ not significant  (N.S.)  is
 indicated.   For the  NCI data only, the female data for any
 maligancy  is  rejected  at p < .05 as being linear in  dose-
response.   However,  small numbers of animals and respondents  in
 some  tumor  categories  make interpretation of this'  test
 difficult.  The second test determines whether the (linear)
 slope  of  the  dose-response curve is different from zero at a
 one-tailed  level  of  significance.  If the p-valuo  for slope is
 small  then  the  inference is that the slope is .significantly
 different  from  zero  (in a positive direction),  indicating a
 tendency  for  increasing values of dose to be associated with
 increasing  values of response.   Not significant (N.S.) is
 indicated  if  the  p-value is greater than OT05." "The  categories
 of "any malignancy"  for males and combined sexes are highly
 significant for slope  at p = 0.002 and 0.005,  respectively.
 For the other tumor  categories  small numbers of animals and
 responding  animals present a problem of interpretation, though
 high significance was  observed  for slope  in  the data for males
 with  leukemias  and combined sexes with malignant lymphomas.

     One additional  test was  conducted on the  dose-response
 data  for any  malignancy to determine whether there  was a
 significant difference  between  the  male  and  female  responses
 across dose levels.  The method  used was  Cbchran's  method of

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standardized  difference  (Gochran,  1954).   No statistically
differences (at an  a-level of  0.05)  were  found.   This test was
primarily conducted  to  see  if  there  would  be  problems in using
the combined data for any malignancy  as a  basis  for risk
extrapolation, and  it was determined  there would be none from a
statistical viewpoint.

     There are several  reasons  for  using  the  "any malignancy"
data as a basis for  risk assessment.   First/  they are markedly
statistically significantly  higher  at the  high  dose,  the test
for positive slope  is highly significant and  there is no
significant departure from a linear  trend.  These data also
have denominators of 48, a larger number than the 24  animals of
each sex, so that confidence limits  an extrapolated dose-
response curve would be narrow.   FDA  used  the identical
categories of total  malignancies  in  Table  2 as  a basis for part
of their risk assessment.  Available  risk  extrapolation  models
do not preclude the  use of data where there are  no
statistically significant increases over control  at any  (or
even all) dose levels,  though  there may be a  substantial impact
on p-values and confidence limits.   Better  discrimination
between  these models also can be obtained  if  there is an ample
range of doses over  which the response is  noted.   Measures  of
goodness-of-fit of  the  models  to  the  available data are  also
more meaningful with a  larger number  of different dose-response
data points.

                               20

-------
     NCI did  not  analyze  the  data for "total malignancies" or


"any malignancy".   Since  NCI  stated  that "under the conditions


of this bioassay,  Aroclor 1254 was not carcinogenic ..."  the


ectablishment of  a  tumor  category where  significance occurs may


seem to be like  "fishing" for statistical significance.  We do


not regard this as  a  serious  objection because there is solid


independent confirmation  of carcinogenicity from the Kimbrough '


study (1975), presented in Table  5,  where the high incidence of
            *

hepatocellular carcinomas was observed 26/184 at 5 mg/kg/day


compared to 1/173 at  control  (highly significant by the Fisher


Exact Test at p < 0.0001) .





     A high incidence of  liver neoplastic nodules was  also


observed by Kimbrough with 146/184 at 5~  mg/kg/day compared to  -


0/173 at control  (so  obvious  that no statistical test  of


significance was  reported) .   However,  like  adenomas,  neoplastic..


nodules are not malignant and the significance of their


appearance is not -entirely clear.  (Personal  conversation  with


scientists in the Oncology Branch).





     A question arises here:,   why  were the  tumor types  between


the NCI study and the Kimbrough study  so different?  The main


tumor types observed  in the National  Cancer  Institute  (NCI)


Bioassay on PCBs were, in order of decreasing incidence,


hematopoietic neoplasms (leukemias and malignant  lymphomas),


liver carcinomas, stomach adenocarcinomas,  and gastrointestinal




                               21

-------
tract malignancies.  On  the  other hand,  hepatocellnlar
carcinomas were the main  tumor  type  identified  by Kimbrough.  A
possible explanation for  this difference is  that two different
Aroclors were tested in  two  different  strains.   The NCI studied
Aroclor 1254 in Fisher 344 rats  and  Kimbrough used Aroclor 1260
on Sherman rats.  We do .not  know what  the  polychlorinated
dibenzoturon concentrations  were in  these  two studies.
(Kimbrough, 1975 and NCI,  1978)   The degree  of  variability
between different strains  within a species can  be as high as
the .degree of variability  between  different  species.  Also,
while the Aroclors are mixtures  they differ  in  both the degree
and structural location of chlorination;  for Aroclor 1254 the
major component (53%) is  C12HSC15  and  for  Aroclor 1260 the
major component (42%) is  C^2H4C^6*
"*>              .        B               
    .The Kimbrough study  will allow  only the crudest forms of
risk modelling as it has  only one  nonzero  dose  level.   However,
there is no question as  to the  statistical significance of the
increase in hepatocellular carcinomas observed  by Kimbrough.
The NCI study will allow  much more mathematically sophisticated
risk modeling and measures of goodness-of-fit of  the models to
the data;  but, standing alone is difficult to interpret,
because of the question of statistical significance of the
various tumor types.  Indeed, NCI  concluded  that  its study did
not establish carcinogenicity.   There is also some  question
about the validity or advisability of using  the category  of

                               22

-------
 "any malignancy".  FDA combined  conclusions from the two


 studies  to estimate cancer  risks  to  humans.  That  is also the


 course that this assessment  follows.


      Table 10  presents maximum likelihood  estimates  and lower


 95 percent confidence limits on  dose  for  a range of  excess


 risks from IxlO"1 (1 in 10)  to lxlO~8  (1  in 100,000,000)


 (hereafter called virtually  safe  dose).   The  data  used here are


 the Kimbrough  data for hepatocellular  carcinomas.   Because


 Kimbrough tested only one nonzero dose  level,  the  only models


 that could be  used were one-hit or simple  linear extrapolation.


 As linear regression-gives nearly the  same results as the one


 hit models at  low doses,  only one-hit  extrapolation  was


 employed.   The computer program  used was  that  for  the


 multistage model/ which degenerates to a one-hit model  when


only one  positive dose level is available.  The  confidence
                                                  "  j ;         
                  -..-.          ...             *
 limits on  these virtually safe doses are- tight,  roughly within


 a  factor  of 1.5 of the point estimates at  a risk of  1x10"^ (1


 in 1,000,000) .





      Table 11  presents a similar  range of  excess risks  of any


 malignancy over background based on the. NCI PCS  Bioassay,


 derived using  five of the most widely known and  used


 extrapolation  models:  The multistage, logit, probit,  Weibull,


 and gamma-multihit.   The  logit and the probit ordinarily  are


 expected  to give similar  results, because of their similar


 functional form.  Estimates from the one-hit model were similar



                               23

-------
to those from the multistage  model.   Simple linear


extrapolation is approximated  by  the  lower confidence limits on


virtually safe doses  (that  is,  upper  confidence limits on risk)


from the multistage model.  Two  types  of  background were


assumed for incorporation  in  all  models  except thr


multistage.  Independent background  implies that any ongoing


background carcinogenic processes are  independent of the


carcinogenic response  induced  by  the  administration of the


carcinogenic agent under study.   Additive background implies,


on the other hand, that cancers  induced  by administration of


the chemical under study add  to  already  on-going carcinogenic


processes,  as if arising from  an  effective background dose,


acting by the same mechanism  and  producing similar types of


tumors.  It is not cltar at this  time  which of these two is the


more valid assumption, therefore  for  the  four models available
            **

that consider both, types of background,  both.are presented.


The multistage model  is consistent with  both assumptions so,


traditionally, one does not speak  of  it  as either additive or


independent.  Goodness-of-fit  p-values were also calculated to


give an idea of the fit of  the model  to  the data.






     It can be seen from of Table  11  that the estimates of


virtually sa-fe dose at a risk  of  IxlO"6  (1 in 1,000,000)  from


the independent background  models  vary a  million fold from 10~2


.for the probit to 10~8 for  the gamma-multihit.  The additive


background models, including  the  multistage model,  are all in




                               24

-------
the area  of  0.16  x 10~4 to 0.17 x 10"3 mg/kg/day.   The

goodness-of-fit  test  results show the multistage model to  be

the model  with  the best fit to the data  (p > 0.9000)  and the

additive gamma-multihit,  the worst fit (although it  is still.

quite  adequate)  at p  = 0.5391.




     Tables  12  and 13  present the results -of two suggested

methods for  placing confidence limits on virtually  safe dose,
                                      *
one by using  the  variance  of log-dose,  the other by  using  the

variance of  the  reciprocal of dose.   The confidence  limits in

Table  12,  based on the variance of log  dose are generally  much

wider  than those  in Table  13, based on the variance  of the

reciprocal of dose.   Confidence limits  from the independent

models vary  widely, while  thos.^ from the additive models are

within factors of  5 of each other by the two methods  and are

within factors of  4 -to 20"of their maximum likelihood  estimates

at a risk  of  IxlO"6.




     The confidence limits for  the multistage raodel,  calculated

by a method  unique  to  that model,  are within a factor  of 1.8 of

its maximum  likelihood estimate of virtually safe dose  at  a

risk of IxlO""*5.   Thus  the  multistage confidence limits  are much

more narrow or  "tight-"  See Figure  1,  which shows upper

confidence limits  on risks,  rather than lower confidence limits

on dose.
                               25

-------
     Table  14 presents,  for a range of excess risks from  1x10"^

to IxlO"8, a table of maximum likelihood  estimates for leukemia

alone over  background based on the NCI PCB bioassay.  Leukemia

alone was chosen because  of the  high percentage of pathology of

this type in the NCI bioassay.  The risks predicted by the  same

range of independent and  additive  background models are within

factors of  5 of similar  estimates  based on any malignancy.

Again estimates of confidence limits on virtually safe dose

based on the variance of  log dose  vary more widely than

estimates based on the variance  of the reciprocal of dose.  The

multistage estimates are  also narrow and  this model produces

the best fit among the models examined.  Overall there is much

consistency between the  estimates  based on any malignancy and

those based on leukemia  alone.

            "              "*"                                 .     -
  -'. We "now consider "-how  estimates of virtually safe doses  for

risk of hepatocellular carcinoma from the Kimbrough study

compare with estimates of  virtually safe  dose based on any

malignancy or leukemia alone from  the NCI study.  Based  on  the

multistage, the best fitting model,  the maximum likelihood

estimates from Table .10  compare  very well (within a factor of 1

to 2) with each other, the  confidence limits within a factor of

1 to 3.  Tt seems then that it makes little difference which

study is used, Kimbrough  or NCI, to base  quantitative estimates

of cancer risk to humans.   The decision on which study to

choose for extrapolation  might be  based on the likelihood of


                               26

-------
exposure  to  a  particular type of Aroclor since apparently  the

tumor types  were  different for tests of Aroclor  1254  and  1260,

though strain  of  animal  may have been just as  important.   The

extent to which one  expects perfect site concordance  would  also

dictate the  choice  of  a  study.  Remember that  FDA used  both

studies in its  risk  assessment of PCBs.   .        -            ..




     With these preliminary remarks and tabulations,  we use for
                                                  *
exposures of various subpopulations provided by  the Exposure

Assessment Branch,  Exposure Evaluation Division  of OTS  to

estimate additional  or excess lifetime risk.  The NCI data

(used by  FDA)  and the Kimbrough data (used by  FDA, CAG, and

OTA) are used  as  the bases for extrapolation.




     Table 17  presents the excess or additional  lifetime risk

estimates based on.,  total  malignancies  in the NCI study.  The

model used to  derive these excess risks was the  Crump

multistage model and program  (used  by  FDA,  CAG, and OTA in

their assessments).  A species conversion factor of

approximately  5.85 was used for the transformation of rat risks

to human risks; i.e., humans  are presumed to be roughly six

times as.sensitive to carcinogenic  effects  of chemicals as

rats.  The estimated exposure duration in years was used to

modify the risk estimates  for the proportion of an average

human lifespan of 70 years that an  individual in a given

exposure category might  be exposed  to  PCBs.   If the exposure



                               27

-------
duration was 38.5 years,  as  in  the  case  of  exposure
loading/unloading a liquid assuming  PCBs  are  present in the
liquid at 25 mg/kg then  the  cancer  risks  were reduced by a
factor times 38.5/70 or  0.55 of  their  original  size.  (It would
be best to base such proportion  of  lifetime calculations on
results from a differential  exposure study;  however, none was  .
available and this simplistic multiplication  factor is
currently the state-of-the-art  in  this area.)   Both "most
likely" or point estimates of excess cancer risk and 95 percent
upper confidence limits  on excess cancer  risk  are presented.
The upper confidence limits  from the multistage model exhibit
linearity at low exposures.  They also assume  additivity.
Additivity, as mentioned  earlier, assumes  that  the effect of a
carcinogenic agent is to  act through the  same mechanisms as
that operating for background process.; The upper confidence
limits are not markedly  more conservative .than  the point
estimates of risk in the  case of the NCI  total  malignancies
category.  Many other factors mentioned in  the  other Agencies
^-isk assessments influence the  results.   Among  these are the
dissimilarity between residues  in fish and  water and Aroclor
1245, the levels of PCBs  in  human adipose  tissue,  and the small
sample sizes in the NCI  study.

     The extrapolation distance  between the lowest experimental
dose in the NCI study (1.25 mg/kg/day, the  lowest  of any level
in either the NCI dataset),  and  the highest and lowest exposure

                               28

-------
levels  is on  the  order of from 6 to 45,000,000/000.   This  is  a
very wide range.   Keep in mind that generally the  further  the
distance over  which  risks are extrapolated the less confidence
one could have  in  those  risk estimates, and that errors could
go  in either direction.

     The assumptions  used'to derive the exposure levels shown
in  Table 17 are discussed in the exposure assessment  for
incidentially  - produced  PCBs (Versar 1983).  One  purpose  of
the exposure and  risk  assessments is to provide guidance in
establishing a permissable  level of PCBs in other  chemicals.
Using conservative assumptions,  the exposure assessment
estimated the  upper  limits  of exposures that may result when
PCBs are present as  impurities in a variety of chemicals and
products^ at levels of  50  ppm,  25 ppra,  and 2 ppm.    The exposure
levels in Table 17 correspond  to the upper limits of exposure
for the various scenarios when the concentration of PCBs is
25ppm.  Few, if any,. individuals will  be exposed  to these
relatively large amounts  of  PCBs.  Thus, the maximum likelihood
of excess risk in  Table 17  applies to  highly exposed
individuals.  The  excess  carcinogenic  risks to typical members
of  the exposed groups  are  believed to  be no higher than those
in  Table 17 and are probably much lower.
                               29

-------
                          References


Armitage, D.   (1955).   Tests  for linear trends in
proportions and  frequencies.   Biometrics, 11, 375-385.

Bioassay of Aroclor  1254  Nd  for possible carcinogenicity.
Carcin. Tech.  Rep.  Ser.  No.  38.   RHS Publ.  No. (NIH) 78-
838.   1978.

Cochran,. .G.   v!954) .   Some  methods or strengthening the
common  x tests.   Biometrics  10, 417-451. -

Crump, K.S., Guess,  H.A. ,  and Deal, K.L..  1977.   Confidence
intervals and  tests  of  hypotheses concerning dose response
relations inferred  from animal carcinogenicity data.
Biometrics 33:   437-451.

Crump, K.S., and Masterman,  M.  "Assessment of carcinogenic
risks  from PCBs  in  food."   April 1979.   Working  Paper IV.

Crump, K.S.  An  Improved  Procedure for  Low-Dose  Carcinogenic
Risk Assessment  from Animal  Data.  Jou-rnal  of Environmental
Pathology and  Toxicology,   vol.  5, No.  2, 1981,  pp.675-684.

Cordell, F.  June.  1982.   "Risk assessment in a Federal
regulatory agency :   human  consumption of some species of
fish contaminated with  polychlorinated  biphenyls .( PCBs)."
Environmental  Health Perspectives.- Vol. 45.   /  .

Environmental  contaminants  in food.  U.S. Off ice. of '  ,
Technology Assessment.   December 1979.       '

Humphrey, H.E.B.   1977.   Evaluation of  changes of the level
of polychlorinated  biphenyl's (PCB) in  human tissue.  Final
Report oh FDA  Contract  233-73-2203.

Industrial Bio-Test  Laboratories, Inc.   1971.  Reports to
Monsanto Company.   Two-year  chronic toxicity with Aroclor
1242,  1254, and  1260 in albino tats.  Unpublished reports.
November 12, 1971.   IBT No.  B7298.

John T. Gart,  Kenneth  C.  Chu, Robert E. Tarone,  "Statistical
Issues in Interpretation of  Chronic Bioassay Tes^.s  for
Carcinogenicity," Journal  of  the National Cancer Institute
Vol. 62, No. 4,  April  1979.

Johnson, R.D. ,  and  Marshe,  D. D.   1977.   Pesticide and other
chemical residues  in total  diet  samples (XI).  Pesticide
Monitoring Journal  11:   116-131.
                            30

-------
Kimbrough,  R.D. ,  Squire,  R.A. ,  Linde, R.E., Standbury, J.D. ,
Mental,  R.J.,  and  Burre,  V.W.  1975.  Induction of liver
tumor  in Sherman  strain female  rats.  J. Nat'l  Cancer
Inst.   55:   1453-1459.

Mantel,  N. ,  Bohidar,  N.R., Brown, C. C. ,  CLminera, J.L. ,  and
Tukey,  J.W.   1975.   An  improved Mantel-Bryan procedure for
the  "safety"  testing  of carcinogens.  Cancer Research  35:
865-872.

Miller,  R.G. ,  Jr.   Simultaneous statistical inference.
McGraw  Hill  Book  Co.,  New York  1966, pp.6-10.

Morgan,  R.W.,  Ward,  J.M., Hartman,  P. E.  "Aroclor 1254-
induced  intestinal  carcinoma  and adenocarcinoma in the
glandular  stomach  of  F344 rats."   Cancer Research, 41, pp.
5052-5059,  1981.

Rai, K.  and Van Ryzin,  J.  Risk assessments of toxic
substances  based on a generalized multihit  dose response
model.   Proc.  SIMS  Conference Alta,  Utah,  June 1978:   26-30.

USEPA "Ambient Water Quality Criteria for  Polychlorinuted
Biphenyls"  EPA 440/5-80-008.  October 1980.

USEPA "Water Quality  Criteria Documents; Availability" Part
V Environmental Protection Agency Friday.,  November 23, 1980,
pp.79339, 79353.                                       .

Versar,  "Exposure  Assessment for  Incidentally  .Produced  .    -
Polychlorinated Biphenyls (PCBs)",  Washington,  D. C.  U.S.
Environmental  Protection  Agency,  Office of  Toxic
Substances  68-01-6271,  1983.  (Draft Final Report)
                            31

-------
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-------
Table I-  C2J31 s Table  for Water  Quality Criterion of PC3s

PC3 Exposure        Lifetime  Risk  Levels  and Water Quality Grit*

                                             10"6
10'
                                                             10
                                                               -5
   2. liters  of
   drinking  water
   and consumption
   of 6.5g contaminated
   fish and  shellfish
   per day*
                             0.0079  ng/1    0.079 ng/1   0.79 ng/1
   Consumption of fish
   and shellfish only*
                             0.0079  ng/1    0.079 ng/1   0.79 ng/1
*Approximately 99% of the PCB exposure results  from aquatic
 organisms, which exhibit an average bioaccumulation  potential
 of 31,200-fold.  The remaining  1% of OCB exposure  results from
 drinking water.
                              34

-------
      2:  Aiimal Data Osed for Risk Extrapolation to finnans in FDA ^ssessnent
                                       Dose of roclor 1254 fed
Aiimal Studies
pan 0
nnAg/day 0
25
1.25
50
2.50
100
5.00
NCT aioassay - Fischer                .            \
 .  Fischer Rats fed            .       .
  Total Malignancies                       /

      Males            .            5/24              2/24         9/24        12/24
      Females                      4/24-           "  13/24         8/24         9/24
      Qanbined                     9/48             15/48        17/48        2J/48

Liver Ccircinona & AJenonas
      Males                        0/24             0/24         V24         2/24
      Fenales                      0/24             0/24         1/24         2/24
      ODtnbined                     0/48             0/48         2/48         4/48

Hematopoetic Nsoplasms
      Males--    "                   3/.'4             2/24          5/24  -       9/24
      Eenales                      4/24   ,  '.        6/24       '   6/24         6/24
      Oanbined                     7/48     "        8/48         11/48        15/48
                                      35

-------
Table 3:  Cbper Csnfidencs Limits (99%1 on Lifetime Risks* of Oncer in Eaters of  Fish Spe<
       Studies
en which risks
are based
               50th Percentile Eaters
                                901
Jsuning        /ssuning   ssuning    ssuning
Nb Tolerance    Tolerance . Tolerance   Tolerance
                * 5 ps
                                 Lake**
                           USA   Michigan
                               fi-6
                                         1 ppa
                      Assuning
                      Ma Tolerance
                            Lakes* "
                      USA
Kimbrcugh - Pats
Liver
Nd Bioassay - Tbtal
Malignancies for Male
and Eemale
1.3    13.4   .    1.2
4.1    58.0       3.7
0.8
2.7
                                         0.5
3.4    4.1.. 4
                                         1.6       10.6
                                             36

-------
>le 31 Upper 'Confidence Limits (99%) on Lifetime Risks* of Cancer in Eaters of Pish Species of Interest

imal Studies !
which risks '
) based


i


.ibrough - Rats
er Carcinoma 
[ Bioassay - Total
i Llgnancies for Male
j Female
I Bioassay - Liver
rcinomas and Adenomas
r Male and Female
[ Bioassay ;
natopietic for
ie and Female-
Mi risks are lifetime
i
50th Percent lie Eaters
i
Ass, uning Assuning A3 sun ing"
to jlblerance Iblerance Iblerance
 Lake** = 5 ppn  2 ppn
USA Michigan .
i  .
l i
1
1.3 18.4 1.2 0.8
1 i;

4.1 58.0 37 2.7


0.9 12.75 0.9 0.6


2.7 38.25 2.4 1.8 ,
risks computed as rates per 100, 000 of

90th percentile Eat

Assuning Assuning Assuning
Iblerance to "tolerance Iblerance
= 1 ppn  Lake** = 5 ppn
USA Michigan


., : .
0.5 3.4 41.4 3.1


1.6 10.6 129.2 9.8


0.4 2.5 30.5 2.3
.

1.1 7.0 85.3 6.5
the population at risk.
Hisk calculated for Lake Michigan sportsfish eaters who consume an average of 1.7 jjyAg/day pen
>r 3.9 iigAg/day at the
90th percentile. Risks in other areas
having similar sportefish consuiption
and PCB contamination are probably similar.
! i
i
! i.
i
i 
i

!

!
37,

i
i

i








n PDA Assesanent

rs

ssuning Assuning
blerance Iblerance
2 ppn = 1 ppn




2.3 1.4


7.2 4.4


1.7 1.0


4.7 2.9













-------
ible 4t   Upper Cbnfidence Limits on Number of New Cancers per Year in Eaters of Fish Species of  Interest i
                                                                n FDA Assesanent
ilmal
zudles on wliich
isks are based
50th Parcentile Eaters
90th Perce
                                                                               ntile Eaters
Assuning
NJ Tolerance
      Lake**
USA   Michigan
Assuning   Assuming    Assuning
Tblerance  Tblerance   Tblerance
 5 ppn    = 2 ppn     = 1 ppn
Assuning
No Tblerance
      lake**
USA   Michigan
                                                    Assuning
                                                    Tolerance
                                                    = 5
          A3sunIng    Assuning  ,
          tolerance   Tblerance
          3 2 ppn     = 1  ppn

imbrough - Rats
Ivor Carcinoma 6.2 10.4 5.8 3.8' 2.4 16.3 23.4 14.7
Q Bloassay - Total
alignancies for Male .
nd Female 19.6 32.8 17.6 .12.9 7.6 50.6 73.1 46.8
"
Q Bioajsay - Liver
arcincmas and Adenomas
or Male and Female 4.3 7.2 4.2 2.9 2.0 12.0 17.3 10.9
Q Bloassay
smatopoietic
or Male and Female 12*9 21.6 11.4 8.6 5.3 33.4 43.3 31.0
f
All risks are the increased nunber of cancers per year for the population at risk (15.2% of U.S. populat
considering a 70 year life span.
*Dl air ra1 /-*! at*orl fr\tr I* nlrn Ml r*Klrtnn arwtt*l-ci f4 oH cal-^fr-a uiKrt r*r\r\atma ark nttc\-=u-ci 1 f unAtr* /rlatt Dr*O

10.0 6.7
34.3 21
fl.O 4.7
22.5 13.8
on)
or  3.9  pgAg/day at tho 90th percentile.  (4,000,000 people assured exposed).   Risks may be similar for
sportsfish eaters in other areas) but data not available to make estLnate.
                                                          38

-------
Table 5:  Data sets used by Qnjnp for CTCA in calculating virtually safe coses



Data Set No.I Kiabrcugh-jt^aL. (1975)  rat study with Acclor 1260

                           fepatocellular carcinonas

Dietary level    .      No. of animals          No., animals with fepatocellular carcinomas
(pan)    (mg/kg/cay)

  0             0      . -     173                        .   .      1
100     .      5.0    ' .       184                                26    


Data Set No. II-Kimbrough e^^  (.1975)  rat study with Acoclor 1260

                            Liver neoplastic nodiles

Dietary level  .        No. of animals          No. of animals with Neoplastic nocules
(ppn)    (mg/kg/cay)

  0            "0           173                                a
100           5.0        '  184                               146


Data Set No. ni-Incustrial Bio-Test rat experiment with Aroclor 1260

                " .          liver neoplastic nocules

Dietary level       -  No. of animals          No. of -animals with Nsoplastic nocules
 (ppa).    (mg/kg/day)         .   '

  00              23                                1
  1           0.05           25                                0
 10           0.5            23                 .               9
100           5.0            27                                7
                                         39

-------
   le 6:  Virtually  safe doses ccnputed by Crunp for OTA fran data in Table 5
Data Set
Analytic Method
              la   Etofait
              Ib   CneHit and
                   Multistage

              Ila  Brobit
              Hb  Cne-Hit and
                   Multistage

              Ilia Probit
              mb cne-Hit
                   Multistage
Maximum Likelihood
estimates of dose in
ppb corresponding
to extra risk o
extra risk of
Virtually safe doses
(lower 95% confidence
 bounds for dose) in
 ppb. corresponding to
                                    KT8
                                     ICT5
                            10-
         lor6
10'
  ,-5
0069
00063
0046 .
0046
.636
.063
.465
.465
6.36
.634
4.65
4.65
1.96
.0051
.025
.00055
.176
.00235
.00205
14.2
.511
.180
.0511
1.29
.235
.205
43.6
5.11
.552
. .511
3.97
2.35
2.05
                                           40

-------
Table 7.  Estimates of lifetime extra risk io hunans of hepatccellular carcinona
          based en a one-hit model (2) to the Kimbrough et'al.  (1975)
          rat study (appeared in OTA docunent)


                                       Risks calculated fron converting"- honan	
                                       dose to animal dose en the basis of

Hunan PCS Dosage                       gen in diet          mg/frg/day

3.3 u3/cay                              1/328,000           1/764,000
(1976 Total Diet Study)                 .                            -   .

8.7 yg/day                              1/123/000          ' ]/2S8,UOO
(1975 Total Diet Study)               '         '         

127 yg/day                              1/3,000             1/20,000
(A/g. intake of people consuming
more than 24 Ibs./yr. I^ke Michigan
fish, aumphrey (1977) 
                                             41

-------
Table 3.  Extra lifetime risks of cancer associated with consumption of PC2s
          in food (appeared in CIA docunent)


                                Extra lifetime                Upper limit of new
Dose (ug/day)                     risk/100,000                    cancers/year


     9.2  .              .           4.4             		       21
     14.9                          7.2                              34
     20.1C                          9.8                              47

coat3       -                               "..-                           .  '
     3.3d            '               0.13                              4
     8.7                           0.35                             11 '
     127f                        -5                      .          

"Based on Md bioassay and total malignancies  for males and females.
^Based on Kimbrough (1975)  study and hepatocellular carcinomas,
C8ased on highest consuners (90th percentile)  of  fish species contaninatecl with
 PCBs if tolerance established at 1.2 of 5  ppnu
(jBased on FDA Total Diet Study.  1976.
Based on FDA Total Diety Study.  1975.
'Based on average intake of people consuning more than 24 Ibs/year Lake Michigan fish.
                                           42

-------
Die 9:  Ail ma I Data Used for OTS Risk Extrapolation to I lama ns*



lignancy Category
taimals Par Dose Ifivel**

{ Malignancy
les
nales
nblned
ukanias
les
males
nbined
lignant Lymphomas
les
males
nibined
ver Carcinoma
les
males
mblned
omach Adenocarcinoma
les
males
mbined (original report)
mbined (Morgan et al.)
PP"
in feed 0
ihgAg/day o
5/24
4/24
9/48
3/24
4/24
7/48
0/24
0/24
0/48
0/24
0/24
0/48
0/24
0/24
0/48
0/47
25
1.25 .
2/24 (N.S,)
13/24 (.0093)
15/48 (N.S.)
2/24
6/24
8/48
0/24
0/24
0/48 
I
0/24
1/24
V48
0/24
1/24
1/48
1/48
, 50
2.50
9/24 (N.S.)
8/24 (N.S.)
17/48 (N.S.)
5/24
6/24
1V48
0/24
0/24
0/48
J/24
0/24
1/48
1/24
1/24
2/48
3/48
100
5.00
12/24 (N.S.)
9/24 (N.G)
21/48 (.0074)
8/24 (N.S.)
4/24 (N.S.)
12/48 (N.S.)
1/24 (N.S.)
2/24 (N.S.)
3/48 (N.S.)
2/24 (N.S.)
0/24 (N.S.)
2/48
0/24 (N.S.)
0/24 (N.S.)
0/48 (N.S.)
2/48 (N.S.)
Risitiye
Slope
0.002
(N.S.)
0.005
0.014
N.S.
0.080
, 0.063
0.015
. 0.004
0.030
N.S.
0.016
N.S.
N.S.
N.S.
N.S.
P-Value
p-va
frc
N.
P
N.
N
N.
N
N
N
N
N
N
N
N
N
N
N
***
lue for departure
n linear trend
S.
< .05
S.
S.
S.
S.
S.
S.
S.
S.
S.
S.
S.
S.
S.
S.
                                                             43

-------
 Sable 9  /ftimal Data Used tor OTS Risk Extrapulation to Hunana*  (Continued)
lalignancy Category
Jastrointestinal Tract
Malignancies (including
Jejunum, Cecun, and
Stomach
1ales
females
Xxnbined (original report)
Ddmbined (Morgan et al.)
in feed 0
mgAg/day 0
0/24
0/24
0/48
0/48
25
1.25
I
0/24
1/24
1/48
1/48
taimals Per
50
2.50
1 !
2/24
1/24
3/48
4/48
Dose Level**
100
5.00
1/24 (N.S.)
0/24 (N.S.)
1/48 (N.S.)
3/48 (N.S.)
P~
Positive p
Slope
N.S.
N.S.
N.S.
0.044 1
/alue***
value for departure
from linear trend
J.S.
M.S.
M.S.

  *From the National Cancer Institute bioassay of Aroclor  1254
   except as noted.   Morgan et  al.  (  Cancer  Research 41, 5052-5039,
   December 1981)  re-examined the whole-tissue specimans of startach
   taken frcm the  NCI bioassay  and  presented malignancy data per combined
   sexes only.

 **Mjmbers in parenthesis are Fisher  Exact Test p-values for statistical
   significance over control.   Hie  Bonferroni ineojuality was employed to correct
   for lowered p-values due to  multiple comparisons with the same control group.
   N.S.  indicates  not significant at  thea =  0.0500 level.

***1he technique used to derive these numbers canes from (bchran (1954) and Annltage
   (1955).  If the p value  for  positive slope is small the Inference is that the slope
   is significantly  different frcm  zero (in  a positive direction), indicating that there
   is a  tendency for dose to be associated with increasing values of response.  Otherwise
   N.S.  (not significant) is indicated if the p-value is greater than 0.10.  If the p-value
   for departure from linear trend  is small  the null hypothesis of
   linearity (or whether the association between dose and  response is a
   linear one) is  rejected.  Otherwise N.S.  is indicated.      .
                                                           44

-------
labl 10
                                                               Exoit Rlik to R*l ol lUpatocal lular  Carclnoo* Ovor  Uackyround
                                                                          (0t*4 on Klabrough PCB Bloattay)
Mod* I
Multlttag*
  (On*-tt*g*l*
                    |.0006-OI        t.O.IOt-02        I.OOOE-0)       I.OUOE-04        I.OOOC-OJ        I.OOOE-06       |.i)OOE-OI        I.UlOE-Oa
                                                                  LlkcllbooJ Etl*lt  ol  Virtually  Sal*  Oat* tor  Halt
0.miOOE02    0.69ilEOI    0.6t6TO}E00     0.6B6192E-OI    0.666J6U-02    0.6B6J3Bt-0>     0.6061 J8t-04    0.6 16 J)B-01
                                                    tit On*-$|il*d lo.ar Coaf|  an  Virtually Sol* Ooiat lor Rait (oy/kg/dayl
Multlttag*
  lUna-ttagal*
0.324'i2Ei02    O.J0029JOI    0.4B026E00     0.4J80|E-OI    0.47)IE-02    0.497JI6E-OJ     0.487IJ6E-04    0.
9II76E-OS
III* ultlttay* nodol dtgnnoral of  to  Ilio  tpoclllc <:a>* ol th* one-hit odul ahen  only  on*  potlllv* 4as lav*l It avallabla.
                                                                        45

-------
     labl* II
                                                                                 I
                                                                   Exceii Hltk  |o >ia It  o4  Any  Malignancy Over  Background
                                                                              (Bated on  NCI  fCU Bloattay)
Hod* I
                    I.OOOE-OI
                                    I.OOOE-02
                                                     .OOOE-03
                                                                    I.OOQE-04
                                                                                     I  030E-03
                                                                                                     I.OOOF-06
                                                                                                                     I.OOOE-OI
                                                                                                                                      I.OOOE-08 '
                                                                likelihood Eftlaat* ol Virtually Sal* Dot*  for Rail  lag/kg/day)
Goodn**t ol III
!* p-value'
Multlttag*
                   0.338381E402     ,3373694EOI    0.333443E00    0.333234E-OI     0.333133E-02    0.333233E-03    0.333233E-04    u. 333233E-103     >0.000
Independent ' .
Problt" O.I88339E02 O.II|OI7EOI O.I43637E400 0.276096E-OI 0.638313E-02 O.I82634E-02 0. 367* 12E-03 O.I9260IE-
i
Independent
loglt" 0. I836|)E02 0.486|19E00 0. I3I306E-OI 0.47I073E-01 O.I3I28IE-04 0.478783E-06 O.I3I330E-07 0.479380E-
Independent
Nalbull" 0. I79320E02 0.327304EIOO * 0.634606E-02 0. I3I939E-03 0.266236E-03 0.337I92E-07 0. I06392E-08 0.2I8707E
lnd*p*nd*nt GBMM*
Hultlhlt" 0.939I99EIOI O.I13339E-OI 0.338I4U-04 0.494380E-OI O.I34404E-09 0.260I33E-I2 0.303551E-I3 0.97467JE
Additive
Problt" 0. I93480E402 0. I23692E40I 0. I20492E400 0.1I9983E-OI 0. II9934E-02 0. II9929E-03 0. II9929E-04 0. II9928E-
Addltlv* '
Loglt" O.I92963EI02 O.I23398EOI O.II7993E00 0.|UA3E-OI O.II74IJE-02 O.II7407E-03 O.II7407E-04 O.II7407C
Additive
Hclbull" O.I90640E<02 O.II3363EOI O.I09303E00 O.I0893IE-OI 0. I08874E-02 0. IOR869E-03 O.I0886UE-04 0. 1088601-
03 0.8632
09 0.1801
10 0.8937
18 0.6784
1)3 0.8336
1)3 0.8349
03 0.8632
\
Additive Gao*i* . . ,
Multlhlt" 0.2I3479E02 O.I66643EOI O.I620IOEtOO O.I6I348E-OI O.IAI302E-02 O.I6I498E-03 O.I6I497E-04 O.I6I499E-03 0.3391
?  .
 'Any p-yalua yral*r than 0.30  Indicates  an  adequate lit ol the node I lo  III*  data,
"In nany experiments the res^onte  ol  lotereil  alto occurs pontaneouiIy In control  anlaol*.   lull  background >ay b* aisuaiad  lo b*  ellhor  lnd|>*ndenl  ol  Hi*
  Induced raiponiei or additive  In    nechanlitlc Banner.  II In* apontanfoua and  Induced  r**pon*  *r* **iu*)*4 lo b* Independent,  than  Ih* |>robablllly ol
  ob*rvlng  retponi* ol either  typ*  at dot* d It  given byi  PMdl - q   (I - q) Plill,  xh*r* 0 <  q < I donate* th* tponlaneuut background rale.   Under  Hi*
  addltlvlty *u*ptlun,  th*  background r*tpont* *>*y b* contld*r*d  arising  Iron  an  *ll*ctlv* background dos* * > 0, l|h P*ld)   P(d  *  l.   Although  Ih*
   anner In uhlch background  r*tpont*  It accommodated It crucial, th* extent to h^^  Independence  or *ddltlvlty It Indicated by llhor  biological  lefliVv  or
  CKpor ln|^^^data It aomewliot  unclear at  th 11 tin*.
                                                                                  46

-------
l.bl. 12
               9).Of Ona-Sldad Loxor Conlldanc* Lloltt  on  VIrtuaI Iy  SaI a Oo* lor fUtt In ig/kg/day  In  lob I a  II  ttatad on th* Variance ol  Loj-Uoni
                                                                         (Baiad  on  MCI  PC6  Qloatiayl          '                              !
Nod* I
                    I.OOOE-OI
                                    I.OOOE-02       I.OOOE-OJ
                                                                     I.OOOE-04
                                                                                     I.OOOE-OJ
                                                                                                     I.OOOt-06
                                                                                                                      t.OOOE-07
                                                                                                                                      I.OOOE-08
Multlttay*
                   0.20I9J6E02     O.I90a09E40l     .0. l897e>E00    0. U68)E-OI     0. I8967JE-02    O.I89672E-0)    O..I89678E-04     0. I896I2E-0)
lnd*p*nd*n|
Problt1 - 0.220746E40I
Loylt* C.II9026EOI
Independent
Welbull* . O.U3I92E40I
Independent Oammt
Nultlhlt* 0. I6914IEIOO


Additive
Problt* (i.260OEOI

Addltlv*
Loylt1 (I.274J34E10I

Addltlv*
Melbull* (l.2)49)aOI
Additive Goa
MulllMI* 0.497889E 1 1 72E-1 1 0.649296E-19 O.I27II3E-46 0.248641E-S4
1
; . i

0.6J4469E-OI 0.34347U-02 0.3)723E-0) 0.3J6484E-04 0.3J640JE-05 0.5J6J96E-06 0.5>6^3-07
' -1
..
1
i
0.370630E-OI 0.4B4I97E*02 0.476910E-OS 0. 476 1 50E-04 0. 41607 2E -05 0. 4 V6064E -06 0.4J6U6i-07
i
i
0.44I988E-OI O.J67162E-02 0.)606I9E-01 O.J39932E-04 0. J39883E-05 0.)i9878E-06 O.J5J)uE-07
i
0. I9091JEIUO 0. I7I334E-OI O.I69708E-02 0. I69323E-OJ 0. I69306E-04 0. I6950JE-05 0. I6:07E-06
la B>ny *xparla*nlr.  In* r*ipont*  ol  Interctt alia occur  >pont*n*outl y  In  control  nlol$.  Ihli background *ay  ba  a>un*i|  to b* allhar'
 lnd*|i*ndnt ol th*  Inducad  rsponsas .or  addltlv* In a nachanlatlc aannaro   M  tno  pontan*out and Inducad rosponi*s  aro  tstuaad to bu
 Indapandont,  lh*n vlic  probability ol  obturvlng a ratponta ol allhar  I ypa  at  do*  d l> glvan byi  PMdt   q    (I  - q>  P(dl,  uliar* 0 < o, < 1
 danol*> Iho aponlaiiaou* bacfcyround ral*.   Uiidar  Ilia addltlvlty oiuaptlon,  th* background roiponi* o>ay  b con>ldrd  at  arltlmj Iron an
 allacllva backyround dot*   >  0,  ullli  P*(dl  - Pld  .  Although th* aannar  In uhlch background ratponsa It  accoanudat *d  It crucial, II 
 axlont to ulilch I mlapandanc*  or  addltlvlly It Indlcatad by althar biological  Ihaory or  oxpar I nan I al data It tonltal  unclaar al Ihlk llua.
                                                                              47

-------
table II
       91.Of One-'iMed  Lover  Conlldonce Llalts on Virtually Sale Doses, lor Rats  In  a>g/kg/day  In  Table II Bated on the Variance ol  the  Heclprocal  ol  Uute
                                                                 (Bated oa NCI PCB Bloasaayl
Model
                    I.OOOE-OI
                                    I.OOOE-02       I.OOOE-OJ
                                                                     i.oooE-04        I.OOOE-OI        I.OOOE-O&       I.OOOE-OI        i.oooc-uo
Mulllatage
                    0.20I916C02     O.I90809EOI    0. I89785E00    0. U9eiJ-OI     0. I8967JE-02     0. I89672E-0)    0. I096I2E-04    0. lt9672E-01
Independent
Problt* 0.999|22EOI
Independent
Loglt' 0.)60906EOI

Independent
Welbull* 0.129801EIOI
Independent Oarja
Hultlhll* 0. I90484EOI
Additive
Problt* 0.6J99J8EOI
Additive
Loglt* 0.634I26EOI

Additive
Wolbull* 0.6J2956EIOI
Additive Gaoma
Multlhlt* 0.874I28EOI

0. I6J994E00 0. I3JI9JE-OI 0.231194E-02 0.4800J7E-0) O.II807IE-OJ 0. J125J6E-04 O.I0187SE-04
< ' . !
0.)98872C-OI 0. II7040E-02 0.269J04E-04 0.6707IIE-06 O.I7490JE-07 0.470661E-09 0. I295J7E-IO
t

0.1701IIE-OI 0.436419E-01 0.6647181-0} 0. I049J9E-06 O.I7J944E-08 0.297762E-|0 0.}2IIOU-I2
i
0. II1728E-02 0. I29I98E-0) 0. I76I77E-OB 0.244809E-II 0.4I7882E-I4 0.68272IE-I) 0. II41I9E-I9

D.)I))I6E00 0.2942J4E-OI 0.2922I9E-02 ' 0.2920I9E-OJ 0.29I999E-04 0.29I997E-OJ 0. ^91 99SE -06
i
O.J0291IE400 0.28I468E-OI . 0.2794I7E-02 0.2792UE-0) 0.279I9JE-04 O.J79I90E-OJ 0. 2JI9 1 90E-06
'..'' i

0.270681E00 0.249I66E-OI 0.247II8E-02 0.2469I4E-OJ 0.246894E-04 0.246892t-05 0. 246n92E-06
.,
0.)2627IE00 0.499J07E-OI 0.496S67E-02 0.496J01E-OJ 0.4621JE-04 0.446279E-OS 0. ^9620 IE-06
In ntny xparlBtnt* lh rctpont*  ol  lntratl  ) >o occurs tpont *nou I y  In control  anlatli.   Ihl  background nay b atu*d to b Illior
 lnd*pndanl ol Ib* Induced roponto  or  eddltlv*  In   cbanlatlc maar,   II  lha  ipontoneoua  and  Induced retuontoi are astuved lo b
 Independent, Ihen the probability  ol  obervln||   reaponae ol either type et doae d la  given  byi   P'ld)  q  II - a,-) PUodll, hore 0  <-i|  <  I
 denotes Hie tpontaneou* beckground rate.   Under  tbe  oddltlvlly aiauaptlon,  the background retpont* *ay be con>lderd aa arltlng lro  an
 ellectlve background dose > >  0.  l Ih  P'(d)  - Pld   x).  Although the' Manner  In uhlch  background  rasponsv Is accoainodalad It crucial,  the
 extent to h I ch Independence or eddlllvlly  It Indicated by either biological  theory  or  exper laental  dale Is iononhal unclear al thlt  Una.
                                                                           48

-------
table 14
                                                                     Excess Risk fo Hats at leukeale Over Background
                                                                            (Based on NCI PCD Bloassayl
Hod* I
                    I.OOOE-OI
                                     .OOOE-02
                                                    I.OOOE-01
                                                                    I.OOOE-84
                                                                                    I.OOOE-0)
                                                                                                    I.OOOE-06
                                                                                                                     i.uooE-oJ
                                                                                                                                      .003E-08
                                                                                                                                  Goodness  el  lit
                                                                                                                                  test  p-velue*
                                                       Maxliuai  Likelihood  EitUate ol Virtually Sale Dot* to Rats |pg/kg/dayl
Multistage
0.873338E02    0.827988E40I    0.t2)601E00    0.02)I7|C-0|     0.82JI27E-02    0.021I21E-03    0.e2JI22E-Q4    0.62JI22E-OJ     >0.100
lndB*nd*ot
  Pr ob11 
                   0.Jam02    0.26J4UOI     O.I2444aEtQ|     0.291421EIOO    0.6J99JU-OI    0.274622E-OI     0.I062-02     0. 186n2t-02    0.6768
lnd>p*ndont
  Log It"
0.a41)IOE<02    0.I62IJEOI    O.JJ86IE00    0.241262E-OI     O.I10I18E-02    0. IH09JE-OJ    O.SIJOJ-05     0. 68692t-06     0.6616
In pendent
  M.lbull"
                   O.B)IUJE02    U.48I62EOI     0.289M4E00    0. U1108E-OI    O.I06IJ3E-02    0.642J9JE-04     0.58906IE-OJ     0.2J55J9E-U6    0.6)1)
Independent Oe
  Nultlhlt"
                   0.886i2E02    0.441I>4E*OI     0.243)22E00    O.I12JIIE-OI    O.J2J29JE-OJ    0.)8420oE-04     0.2I8JO-OS     0.|IIO?E-06    0.6S62
Additive
  Problt'"
                   0.8J7JJJE02    0.566187EOI     O.J44626E00    0.)4249)E-OI    0.342282E-02    0.34226IE-OJ     0.542218E-04     0. 4,22)SE-OS    0.67J9
Additive
 . Loglt"
0.816617E02    O.J6482JEOI    0.}4207IE00    0.98)JE-OI     O.JJ96I2E-02    O.JJ9389E-OJ    0.514S87E-04     O.SJ938JE-05    0.6111
Additive
  Helbull"
                   0.8403'IE02    0.)6I226E0|     O.J17097E00    O.U4II9E-OI    0.334482E-02    0.3J4438E-01     0.314436E-04     0..'44J34-0)    0.6718
Additive Gtmmm
  Multlhll"
0.8JI>30El02    0.6I)6IOEOI    O.J9497IE400     0.39292JE-OI     0.327I)E-02    0.392697E-03    0.592694E-04     0. )<>2690E-Oi    0.6610
 Any p-velue grenter thin 0.30 Indlcetet  en  adequete  lit  ol  the eiodel  to tne dele.
In aany experl>i*nl> th* response ol  Interest  elso  occurs  spontaneously In'control anlaials.  Ihls background aay  ba  assumed  to be eltlior Independent o| the
  Induced responses or acdltlve In a Mechanistic  Banner.   II  Ihe spontaneous and Induced responses ore  assumed  to  be  Independent.  thn the probability ol
  observing a response of either  type  f dose d  Is given byl   P*ldl   n, 4 11 - 4! Pld). Nhere 0 < q <  I denotes  the  spontaneous backyruund rate.  Under  Ihe
  addltlvlty assunptlon, Ihe background response  nay be  considered as arising from an ellectlve background  dose    >  0,  with  P*(d)  - f*('l   ).  Although  (lie
  anner In Hhlch beckgruund response  Is acconuodated  Is crucial,  the extent to uhlch Independence or  addltlvlty  8>  (nd'lcaled by either  biological) theory or
  experlaental dale Is sctaevhat unclear at  this  tlee.                                                                    i


                                                                          49

-------
labl
               91. Ill On*-Slded  Loiter  Confidence Haiti an Virtually Sal* Doses  lor  lUtt  la  g/kg/dey la table |4 Uase4 on the yarlencu  al  toy-Hose
                                                                    (Based on NCI PCS Bloassay)
Had. I
                    I.OOOE-OI
                                    I.OOOE-02
I.OOOE-0)       I.OOOE-04.        I.OOOE-0)        I.OOOE-06
                                                                                                                      I.OOOE-0?
                                                                                                                                      I.OGOE-00
Multistage
                    0.)7i)l)E02     0.1)ie84EOI    0. J14006E 400    0.11K07E-OI     0. 111B80E-02    O.JJJ888E-OJ    0.>afaE-04     0. :i J J888E -0}
Independent
Problt* 0. |7tt40IE<02 0.2407J7E-OI 0.9974S6E-04 0. IO)32lC-01 O.I96042E-01 0.36J3JiE-0 0.2J097JE-IO
Independent
Loglt* O.ia7lt02 O.S27032E-02 0.773747E-06 0. I|29E-09 0. I6I647E-I1 0.2J0974E-I7 0.129II2E-2I
Independent  
Melbull* 0. ia't64IE02 0. J67066E-02 O.JI5628E-06 0.2}'i-|0 0.2I78E-I4 O.IIt||lE-l O.I46879E-J2
Multlhlt* 0. ial4E\02 0.2J77IJE-02 0. I267B1E-06 0.387124E-II 0.248JJOE-IJ 0.|2I977E-|9 0. JSJ026E-24
Additive  ;
Problt* 0. |3l94JE02 0.947604E-OI 0.661969E-02 0.64I149E-OJ 0.6J89J6E-04 0.6J8696E-OJ 0.6JV67IE-06
Additive
Loglt* 0. (6))E-07
0. 31J617E-07
i
0.72|3aE-07
In >aay *prli*nt th' ropant*  ol  Inlarxt  lia occur! tpontnoi(t I y  |n control  nlaalt.   Ih( bickgrouad my b* a*a4  lo  b*  llhar
 lnd*p*ndnt ol III* |qdL^d r>pan>*t  or  addltlv* In a chanlttlc *nar .   II  th  (pontaavous and Induod rciponiot *r* aua*d to  b
 Independent, then the probability ol  abiorvlng a raipont* ol either type at  du*e  d It  given byi  P'ldl > n '(! - i)l Pldt,  hr  0  < <|  <  I
 denote! the ipcntaneouk background rate.   Under  the addltlvlty ettunptlon,  the  background response nay be considered al arltlng |roi an
 ellectlve background dbie   >  0,  llh  P'(d>  - P(d * v).  Although 'the oannar  In "Men  background response Is accovaodal ed  Is crucl.il,  (he
 extent to oh I clt Independence or addltlvtty Is Indicated by either biological  theory  or  experimental  data Is souenlial unclear at this llo.
                                                                         50

-------
fable 16
        91.01 Onu-SI
0. I2Ollt-07
0.49J586E-08
0. 2)(<066E-Oa
0.99<ny exparlaent* the reiponte  ol  Intereit  alia occurs *pont encoutl y  In  control  anlvalt.  Tblt background  y  bo  auaed to be either
 Independent ol thu Induced r*ipon>>  or  additive In  echenlttlc Banner.   II  the  pontnoou end Induced retpontei  are  attuaxl to b
 Independent, then the probability  ol  obtorvlng a retponto ol either  type at  dote  d U given byi  P'ldt - 4    IT- <)1  riiodll,  oltare 0 < 
 ellecllve backgrotnd dote  >  0,  ullh  P*ld)   Pld * ).  Although lh aanner  In. iitiicb background response Is  accoonodalad  Is  crucial,  gi>
 extent  to uhlch I idupandance or addlllvlty  Is Indicated by either biological  tlmory  or  exparlnental data Is  somexliat  unclear  at this I la.
                                                                          51

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' .
Table 17i Excess Lifetime Cancer Risk From PCI) Exposure Derived Using the Multistage Model.
Daalsi NCI Total Malignancies Category
Estimated Individual exposure* Duration of Haxlmtm
Bxpoaure tyi>e Exposure .icenarlo During period or exposure Cl let lino average exposure** Likelihood
|mg>yl| (mg/kg/aay) |mg/kg/da9l (years) Estimates of
Excess Risk
\ .
Ambient
Inhalation o deference scenarios '
o Exposure at the average urban atmospheric level I'.SxlO"1 1.4x10"' 1.4(10'' 70 6.2xlO~7
(5 ng/m1)
o Exposure at the average rural atmospheric level J.5xlO~* 1.4xlO~e 1.4x10"" 70 6.2x'iO~*
(0.05 ng/mj)
o Exposure, ot the PCB level of quant Itatlon for air 69 2. 7x10" J 2.7xlO"J 70 I.2XIO"1
(1ft ug/mj) '
o Exposure t>t a distance of 800 m (0.5 mile) down-
wind of a large capacity chemicals manufacturing
plant with PC Be present In the process stream at ...
25 mg/kg 2.910~J ' l.lulO"6 l.lxlO'* 70 4.9x10"'
o exposure at a distance of 600 m (0.5 mile) downwind
of a largt capacity Industrial Incinerator burning , ,
< wastes containing 50 mg/kg PCOa <2.410~2  <9.4xlO"7 <9.4xlO"' 70' <4.2xlO~'
Ambient
Ingest Ion o Reference scenarios ' '
o Averag< adult Intake of PC Da via food during 197Q . '
as reportud by FDA <6,.9ilO~i <2.7xlO"5 <2.7xlO~5 70 <1.2xlO"5
o Ingest Ion of fish containing 2 ppm of PCBs (I.e.,
the 1977 proposed FUA tolerance level for PC 8s In
the edible portion of fish) 4.75 1.9x10"* 1.9x10** 70 8.410~5
\ . " '

951 Upper
Confidence Limit
on
Excusa Hick
I.OxlO'6
1.0xlO"B
2.010"J
a.ixio"1
<6.9xIO"7
2.0xlO"5
I.4xl0"4
52

-------
Table 17  (Continued)
Bxpoaure type Kxpoeura ccenarlb
Amblant ,
Ingeatlon o Ingestlon cf flah or water obtained from water
bod 1 oo down atrekm of chemical plants discharging
waatewater containing 100 ug/1 of PC Da
o Ingbatlm of groundwater drawn from walla located
down gradient from a landfill receiving waatea
containln) 50 mg/kg PC Do
o Consumers of water contaminated by dlachargca from
a typical aluminum forming plant with 66 general
hydraulic ayatema aeaumlng
- All ayatema contain SO mg/kg PCOa In July 1984
and thereafter
- All ayatvmu contain 1,752 mg/kg' PCBa from July
1984 to July 198S and contain SO ng/kg thereafter
-July 1984 to July 85
-after July 85
o Conaumere of water contaminated by dlachargera
from a typical petroleum refinery with 8 heat
tranafur ayatema aaaumlng
- All ay at fma contain 50 mg/kg PCOa July 1984
to July 1985 and contain 50 mg/kg^ thereafter
- All aysteua contain 176 my/kg PC Da from July 1984
to July 1985 and contain 50 mg/kg thereafter
-July 19B4 to July 85
-after July 85
- All aystena contain 441 mg/kg PCBa from July 1984'
to July 1985 and contain 50 mg/kg thereafter '
-July 1984 to July 85
-after July 85
Eatlmated Individual exposure*
During pe Clod 01! 'ekpoBUre llfefTino average
|mg/yf|
2.710"4
to 110
<7.7xlO"6

4,J10"6 -
to 4.S10~J
1.U10"4
to 1.1x10"*
4510"' -
to 4.5xlO"J
' t
\
l.OxlO"7 ,
to l.lxlO~J
S.OxlO"7
to 2.1xlO"J
l.OxlO"7 -
to l.lxlO~J
i.210~' ,
to S.6xlO"J
l.OxlO"7 ^
to l.lxlfl"1
(ag/kgYdly)
l.lxIO"8 ,
to S.lxlO"1
O.OxlO"10

to l.SxlO"7
to 4.1xlO"6
to l.BxlO"7

to S.lxlO"8
J.OxlO"11
to 9.0xlO~8
to S.lxlO"8
to 2.2xlO"7
to S.lxlO"8
img/icg/
l.lxlO'8 to
S.lxlO-1
<1.0xlO"

1.8K10"10 _
to 1.8x10"'
to 2.1xlO~7
2.110"l ',
to 2.1x10"'

1.2xlO"U
to 5.1x10""
l.JxlO"11
to S.lxlO"8
to S.lxlO"8
1.2xlO~U 
to S.lxlO"8
to S.lxlO"8
Duration of Maximum
expoauro l.lkellhooil
(yeara) ' Batliuatea of
Ktceai Rlak
70 4.9x10"' ,
to 1.1x10"'
70 
-------
Table 17 (Continued)
Eat 1 nated
Exposure type Exposure acenarlo i>urln<| faflod
1
Occupational
Inhalation o lluforonce scenarloa
o Exposure at. the O3HA atandard for VCUn in air .
(1,000 ug/a') 2.1xlO~J
o exposure at the. level of quantl tat Ion' for PCDa
In air (10 ug/n1) 2}
o Expoaura at the HIOSII reconnended atandard for
PCDa In air (1 ug/a1) 2.1
1
o Transfer and handling operation acenarloa  .
o Loading/unloading a liquid aaaunlng PCBa are preaent ,
In the liquid at 25 ag/kg. 6.010~2
o Load InQ/unloid Ing a powder aaaualng PCBa ace preaent ,
In the powder -i 25 ag/kg  2.9x10"'
o Loading/unloading a powder aauunlng conpllance with '
the rtSI'A nuleanr: duet atandard and aaaunlng PCBa .
are pri aunt In the powder at 25 ag/kg 8.8x10"*
Individual ex
ot fiKp6surfi
|B9/K9/nayl
9.0xlO"4
9. OxlO"5
2.1x10"'
1.1x10"'
J.xlO-*
poaure*
LUe'tlue average
|ag/Kg/aayi
5. OxlO"2
5. OxlO'4
5.0xlO"S
1.1x10"'
6.2xlO"7
1.9xlO"5
Duration of
expoauto
(yearat 
18.5
18.5
1U..5
18.5
ia.s
IB. 5
Haxliiua
Likelihood
Kal liiatea of
Exceau Rlak
2.2
-------
Tabla 17 (Continued)
Exposure typu
Occupat lonal
Inhalation
Exposure ticenarlo
o Exposure to fugitive emissions for  worker
stationed sla meters downwind of leaking
equipment assuming PCBs are present In the
emitted chemical at 25 mg/kg
o Expouurd during open-eurface tank operations
(e.g., decreasing tank) assuming tank liquid
temperature of 7S*C and assuming PCBs are
present In the liquid a 25 mg/kg
o Exposure to evaporative emissions during
non-spray coating operations assuming a
coating temperature of 75*C and assuming PCBs
are present In the coating at 25 mg/kg-
o Exposure to paint mists during spray painting
assuming PCBs are present In the binder at
25 mg/kg
o Exposure to paint mists during spray painting
assuming PCBs are present In the solvent at
25 mg/kg
o Exposure to paint mists during spray painting
assuming PCBs are present In the pigment toner
at 25 og/kg
o Exposure to evaporation emissions during liquid
product formulation assuming a liquid temperature
of 25*C. open formulation tanks, and PCB concen-
trations In the liquid at 25 mg/kg
Estimated Individual exposure* Duration of
OurlnQ' pflflod 'of Mpndlire "Lifetime average exposure
Img/yrj  (mg/Kg/aay) |mg/Kg/aayi . (year a) *
9.2*10"^ 1.6xlO"5 ?.OxlO"* 18.5
6.5xlO~2 2.5xlO"6 1.4x10"' 18.5
4.6xlO"! 1.8xlO"5 9.9x10"' 18.5
S.Sillu"11 2.2-10"* 1.2*10"* 18.5
.4xlO"1 2.5xlO"5 1.4x10"* 18.5
tt.2xlO"2 1.1x10"* 6.9xlO"7 18.5
2.510~J 9.axlO"fl 5.4xlO"8 18.5
Hi I Imt.m
Likelihood
Eatlmetes of
Excess Risk
B.exjO"'
.2xlO"7
4.4x10"'
5.1x10"'
6.2x10"'
2.4x10""
951 Upp(
Confldunce Limit
on
Exueus Hlsk
1.0x10''
7.1x10"'
8.8x10"'
1.0x10"*
S.lxlO"7
4.0xlO"8
                                                                               55

-------
Table 17 (Continued)
Exposure type
                   Exposure scenario
     Estimated Individual exposure*            Duration  of    Haxlaja            95% Upper
Pur ImT period 'ot''apBBP?f  Lifetime average     exposure     Likelihood      Confidence Lluli
Ig7ylr'        lag/It<]/dBy|    |ng/kg/day|       (years)       Estlaites of           on
         .                                      .              Excess Risk        Excess Risk
  Occupational
    Innalat Ion
Exposure to alsts during air-blast pesticide
spraying assuming PCBa are present In  the  active
peatlcldo  Ingredient at 25 ag/kg

o Exposure to evaporative ealaalons during  grain
fumigation assunlng PCDa are present  In  the
fumlgant at 25 ag/kg

o Expoi:ui:e to oil mists during operations  such  as
printing and netalworkIng assunlng compliance
with the OSIIA standard for alneral oil nlat and
assuming pCBs are present In the oil  at  25  ag/kg

o Exposure to evaporative ealsslons during  foamed
plast'.cs manufacturing operations assuming  PCDs
are present In the blowing agent (which  con-
stitutes approximately 17 percent by  weight of
the foam formula't Ion) at 25. mg/kg
8.6x10"*        J.JxlO"8    I.8xlO"8



                <6.5xlO'6   <1.6xlO"6




                l.lxlO"5    6.2x10"*





                1.9x10"'    J.JxlO"6
                                                                           2.9xlO~l
                                                                                  ,
                                                                           l.OxlO"1
                                                                                                                            18. S
                                                                                                                             18. &
                                                                                                                             18.S
                                                                                                                             18.5
                                                                                                                                               "9
                                                                                                                                        B.OxlO
                                                               
-------
Table 17 (Continued)
. estimated Individual exposure'
Bxpoaure type Kxpouuce acenarl'b During patioa
img/yri
Occupational
Inhalation o Bxpoaure to evaporative emissions during
plaatlc manufacturing operations assuming PCBs .
are preunnt In the plaatlc at 25 mg/kg 7;110"*
o K.poauie during manufacture of aaphalt roofing <2.1xlO"l
* products to (.4
o Exposure to evaporative emissions during paper
manufacturing assuming PCua are present In waste- 
paper furnish ati
- 12 mg/kg 9.2*10"}
- 5 mg/kg 1.9*10"i
- 2.5 ng/kg . -2. 0*10 .
o Exposure to evaporative emlsalona during paper
manufacturing assuming PCua are present In the
printed Ink of tJaetepaper furnish ati
2 mg/kg 6.0x10"'
- 25 mg/kg 7.5*10~i
- 50 mg/kg 1.5*10"*
o Exposure durlilg rereflnlng of waste oil assuming
PCDs r present. In the waste oil ati
2 mg/kg 7.8*10"'
- 25 mg/kg 9.7*10"*
50 mg/kg 1.9*10-*
oc exposure I. iieflme average
img/Kg/tiay!
2.8xlO"5
<9.0xlO"' .
to 2.5x10"*

7'.8*10"7

2.4.10'*
2.9*10";
5.910"7

l.OxlO"7
1.8*10"'
7.4*10"'
lg/icg/aay
1.510"5
<5.0*10"' to

2.0*10"!
8.4*10"'
4.110"7

l.'6*10"7
1.2*10"7

1.7*10"7
2.1*10"'
4.1*10"'
Duration of
exposure
(years) 
18.5
18.5

18.5
18.5
18.5

18.5
18.5
18.5

18.5
18.5
18.5
Max Inurn
Likelihood
Kat lua tea of
Bxcesi- Risk
6.6i!lO"6
to li.2xlO"J

i.'7i!io;

7.'l'lO"?
1.4xlO"7

7.510~
9.110"7
1.8.10"'
95t Upper
Cunfldunce l.lml
on
B.cuas Hlak
l.lxlO"5
to'l.OxlO"4

6i2xlO''
1.2xlO'7

9.6.10'^
1.2x10';
2.4*10'7

1.1x10'?
1.5*10''
1.0x10''
                                                                               57

-------
Table IT (Continued)
Exposure^ type Exposure scenario
Occupational .
Inhalation o Exposure during garment dry cleaning operations
assuming ?CIa Ire present In the cleaning fluid
at 25 ng/kg
o Sampling and Maintenance operation acenarloa
o Exposure during on-line repair of equipment
leaking gas/fluid containing PCOa at 25 ng/kg
o Kxpoauie during aampllng assuming the proceaa
stream contains PC Da at 25 ng/kgi
o Expoauie while cleaning equipment containing a
fluid In which PC Da are assumed to be present at
25 ng/kg
o Expoauie while repairing equipment off-line
assumlrg the equipment contains a fluid In
which IClla are present at 25 ng/kg
o Bxpoauie during filter removal assuming PCBs
are present at 25 mg/kg
o Expoauie during removal of atlll hot tons
assuming PCBa are present In the stilt
bottoms ati
200 nig/kg
2500 mg/kg
- 5000 tug/kg
o Exposure during cleaning of spilled liquids
assuming PCOa are present In the liquid at
25 mg/.g
Estimated Individual
During perioa or exposure
T9/y 1 l-9/ig/a.,
1.6xlO"2 6.1xlO"7
. 1.7xlO~l 6.6x10"'
1.6 l.4xlO~*
S.OxlO"1 2.0xlO"5
2.5x10"' 9.8x10"'
l.lxlO"1 5.1*10*'

9.8xlO~l 1.8x10"!
25 9*.8xlO"*
i.OxlO"1 7.8x10"*
exposure*
LlieTTmu average
rl (ng/kg/dSJi
1.4xlO"7
1.6x10"'
7.7xlO"5
l.lxlO*5
5.4x10"'
2.8x10"'

2.1x10"?
2.8(10**
S.4xlO"*
4.1xlO"8
Duration of Maximum
exposure Likelihood
(years)  Estimates of
Excess Disk
18.5 l.Sxlft"7
18.5 1.6.IO"6
18.5 1.4:10"5
18.5 4.9>:10~'
18.5 2.4iilO~'
18.5 1.2x10"'

18.5 9.1alO*J
18.5 1.21.10"*,
18.5 2.4:MO~*
18.5 1.9:
-------
Table 17 (Contlimed)
Exposure type Bxpouure scenario
Occupat lonal
Inhalation o Exposure to evaporative emissions for a worker
stationed one meter downwind of a leaking
hydraulic uyatea operating at 75 C assuming
- All aiatnns contain SO ng/kg PCBa In July 1984
and tl.eriiafter
- All aystona contain 1.752 ng/kg PCBa from
July 1964 to July 1985 and contain SO ng/kg
thereafter
-July 84 to July 85
-after July 85
o Exposure to evaporative ewlsalona for a worker
atatlonod throe netera downwind of a leaking heat
tranafei ayatea assuming
- All systems contain SO mg/kg PCBa July 1984
to July 1985 and contain SO ng/kg thereafter
- All syatons contain 176 ng/kg PCBa fron July 1984 
to July 1985 and contain SO ng/kg thereafter
-July 84 to July 85
-after. July 85
- All uyst-jma contain 441 ng/kg PCUa from July 1984
to July 1985 and contain SO ng/kg thereafter
-July 84 to July 85
-after July 85
Eatlnated Individual exposure* '
Dur lnj~p"6r loo or exposure |. IfBlTlna <.vora<
"^g/yri img/icg/aTy) . |IgVxg/dayj
* i "
l.SxlO"1 5.910"' 1.2x10"'
5.J 2.1x10"* 6.2x10*'
l.SxlO"1 S.9xlO"6 6.2x10"'
'
S.8xlO~l 2.1xlO"5 l.lxlO"5
2.0 7.8xlO"5 1.1x10"*
5.8x10"' 2.1xlO"5 l.lxlO"5
5.1 2.0xlO"4 l.SxlO"5
S.BxlO"1 2.1xlO"5 l.SxlO"5
Duration of
ue expoaura
*~ (yeara) 

18.5
1
17.5

.18.5
1
17.5
1
17.5
Haxlnum
Llkellhoud
Estimates of
Excesii Rlak

1.4x10"'
2.7x10"'
2.1x10"'

5.7x10"'
5.7x10"'
5.7x10"'
6.6x10"'
6.6x10"'
951 Upper
Confidence LI*
on
Kxcuaa Hlak

2.4x10"'
4.6x10"'
4.6x10"'

9.6x10"'
9.6x10"'
9.6x10"'
l.lxlO"5
l.lxlO"5
                                                                              59

-------
Table 17  (Continued)
Exposure type Bxpoauru acenarlo
Occupational
dermal o Exposure to hydraulic system operators and
malntcnancn workers assuming
- Ml systems contain 50 mg/kg PC Da In
July 198-1 and thereafter
- Ml systems contain 1,752 ng/kg PCBa from
July 1984 to July 1985 and contain SO
mij/kg thereafter
-July 64 to July 85
-after July 85
o Exposure to heat transfer system operators and
maintenance workers assuming
- Ml systems contain 50 mg/kg PCBa July 1984
to July 1985 and contain 50 mg/kg thereafter
- Ml ayatoma contain 176 mg/kg PCBa from July 1984
to July 1985 and contain 50 mg/kg thereafter
-July 84 to July 85
-after July 85
- Ml systems contain 441 ma/kg PC Be from July 1984
to July 1965 and contain SO mg/kg thereafter
-July 84 to July 85
-after July 85
'.. Eat (mated
 Our Ind per loo c
|mg/yr| '

17..7
620
17.7
'" ' !
17.7
62.1
. 17.7
1S6
17.7
Individual exposure*
>f etpgBOTi CTTBfTisa average
(SgYkg/aay) [g/tg/aayi

6.9x10** 1.8x10'*
2.xlO"? 7.1x10'*.
6.9x10"* 7.1x10'*

6.9x10"* 1.8x10'*
2.4x10"? 4.0x10'*,
6.9x10'* 4.0x10'*
6.1x10'? 4.6x10"*
6.9x10"* 4.6x10"*
Uuratlo-i of
exposure
lyenrs) 

18.5
17.5

18. 5
1
17.5
1
17.5
Max liium
Likelihood
Estimates of
Bxcoa.i Risk

1 .7x10"*
1.1x10"*
1.1x10"*

1.7x10"*
1.8x10"*
1.8x10"*
2.90x10"'
1. 09x10"*
951 Upper
Confidence Llml
on
Excuss Nlsk

2.8x10"* 
5.2x10'*.
5.2x10"*

2.8x10'*
2.9x10'*.
2.9x10"*
4. 8)xlO~'
1.81x10*4
                                                                                 60

-------
Table 17 (Continued)
,
Exposure type Bipoaura scenario
Occupational
dermal
o

i o
0
0

o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
.
-
-
o
Transfer and handling operations assuming PC Be
are present at 25 mq/kq
Loading/unloading liquid
Loading/unloading powder
Processing operations asuuilnq PCBs are
present At 2S mg/kg
Closed process operations
Open surface tank operations
Spray painting operations
Grain tunlgatlon operations
Air-blast pesticide spraying operations
Non-spray coatlna operations
Product formulation operations
Product fabrication operations
HetaKorklng operations
Newspaper production
Plastics manufacture
Dry cleaning of garments
Sampling and maintenance operations assuming PCBs
are present at 2S ng/kg In the process stream
On- 11 nd repair of leaking equipment
Sampling process stream
Cleaning equipment
Off-line repair of equipment
Removing filters
Removing still bottoms asuumlng PCBa are present
In still bottoms ati . j
200 me/kg
2500 i.g/Kg
SOOO >ig/kg
Spill cleanup
Estimated Individual exposure'
During* "fter lod"bf epoatir"
img/yrj


6.0
5.8


1.0
IS
IS
H
?s"
6.0
 .'
IS
IS
15
IS

0.2S
IS
1.0
l.S
1.0

24
loo
600
0.75
(ag/kg/aay|


2
2


1
S
S
1
S
2

5
5
S
5

9
S
1
S
I

9
1
2
2


.4x10"*,
.4x10"*


.2x10"*
.9x10-*.
.9x10'}
.9x10-*
.6x10"?
.9x10"*
.4x10"*

.9xlO"f
.9x10"*.
.9x10"*
.9x10"*

.8x10"$
.9x10"*
.2x10"*
.9x10"*
.2x10"*

.1x10"*
Ixlfl
.IxlO'2
.9xlO"5
Liretlme average
(g/kg/day|


1.1x10"*,
1.2x10'*


.4x10"*
.2x10"*.
.2x10'
.2x10"
.'2xlO~
.1x10"

.2x10"
.2x10"
.2x10"
.2rlO"*

.4x10"?
.2x10"*
.4x10"?
.2xlO"{
.4x10"*

5.1x10"*
6.0x10"*
l.lxlO"2
1.6xlO"b
.Duration of
exposure
(years) 


18
18


18
18
18
. 18
18
18

18
18
18
ia

18
18
. 18
18
18

18
ia
18
18


.5
.5


.5
.5
.'s
.'s
.5

.5
.5
.5
.5

.5
.5
.5
.5
.5

.5
.5
.5
.5
Hax Inum
LlkdllhmxJ
Estliiatua of
Kxcean Risk


S.
S.


2.



.

2.
1.
2.
1.
2.

2.
2.
S.
7.


IxlO"5


8x10"?
4xlO~*.
4x10"'
4x10:*
4ltO"*
1xlO"s

4x10"*
4xlO~*.
4x10"'
4x10"*

4xlO"f
4x103*
4x10"^
dxlO"5

1x10"*
6x10"'
IxlO"1
IxlO"6
95t Upper
Confidence Mi
on
BNUUUS Hlek


9
8








4
2
4
2
4

1
I
9
1


!BXIO"S


.7x10"*
.4x10"!
.4x10"*
.4x10"*
.sxifl-;
.4x10"*
.6xlO"5

.4x10"*.
.4X10"J
.4x10"*
.4x10"*

.OxlO'J
.4x10"*
.1x10"?
.4xlO"|
.7xlO"5

.8x10"*

'.SxlO"1
.2xlO"5
                                                                               61

-------
Table 17  (Continued)
Exposure type Exposure ucanarlo
Conauraer
Inhalation o Exposure resulting from uae of apace deodoranta
aaaumlng PCDa are present In the product at
25 mg/kg
o Exposure resulting from uae of moth control
products as iuiilng PCua are present In the
product at 25 mg/kg
o Exposures resulting from painting the Interior
of a houaa la sum Ing CB are preaent In the
pigment at 25 mg/kg
o Exposures resulting from painting the Interior
of a houaa aaaumlng PCBa are present In a realn
Intermediate at 25 mg/kg
o Exposures resulting from Inhabiting a home with
a newly painted Inferior aaaumlng PCBa are
preaent In the p^.nt pigment at 25 ng/kg
o Exposures resulting from Inhabiting a home with
a newly painted Interior aasunlng PCBa are
preaent In a realn Intermediate at 25 mg/kg
o Exposures resulting from uae of spray paint
aaaumlng PCBa are preaent In a realn or
aolvent at 25 mg/kg
o Exposures resulting from uae of apray palnta
aasunlng PCBa are preaent In the pigment at
25 mg/kg
Eat ! ted
Pur Ing perioa
TBgTFtr
1 7xlO'1 
J.2xlO"2
1.7*10"*
7.710"*
2.610"2
1.2*10"1
2,9xlO"2
2.2xlO"J
Individual exposure1
ot exposure LuBfTme average
lg/g/:10'9
1.8KIO"7
8.4H10'7
3. HitlO'7
J.OalO'8
95% Upper
Confidence Llml
on
Excuaa Hlak
.,..
4.6x10"'
.6lO-
4.4xlO"9
J.OxlO"7
1.4x10''
6.5xlO'7
5.0IO'a
                                                                                 62

-------
fable 11  (Continued)
                                                           Estimated  Individual  eiipoaiite*
                                                      During pecioa 01  e
                                                                  '  "   j
Duration of
 exposure
(years)  
xpoaure typo
Exposure scenario
                                                                         During
                                                                          i^i- B^J y 
       rr   (.ireciue average
|mgvicg/
-------
Exposure type
Consumer
Inhalation
Conaumer
dermal
j Estimated Individual exposure* Duration of Maximum
Exposure acenarlo OUr(n4 peflbd At exposure LlfeTTno avurayo exposure Likelihood
I"5 'V *) lg/Kg/"ay) (g/xg/tiy) lyearat ** eatlmatoa oi
txceaa Disk
o Expoauie resulting from use of peatlclde apray*
aaaumlng PCBa are preaent In the active Ingredient * i .1 i
at 25 mg/kg  2.2x10"* B.CxlO"' i.8x|0~' 55 ).0IU~'
o Expoauie resulting from uae of peatlclde sprays <
assuming PCBa afe present In the Inert Ingredients ! i  t c,
at 21 mg/kg l.lulO"1 4.1x10" l.'xlO  55 1.5:10'e
o Expoauiea resulting from uae of apray
cleunlng/dtalnfactanl producta aaaumlng that
PCBa are preaent In a conatltuent (that accounts
for 50 pnrcent of the weight of the product) at , , , ,
25 mg/kg 2.1x10"* 9.0x10" 7.1x10" 55 ' l.l:ilO"
o Expoaurea resulting from Inhabiting a new home
containing plaallc building materials which are . , .
aeaumed to contain PCBa at 25 mg/kg i.l 1.2x10"* 2.7x10"' 6 l.2clO~&
o Expoaure:! resulting from uae of deodorant soaps ,
aaaumlng PCBa ate preaent In the surfactant at ' , _ ,  _
25 mg/kg J.lxlO"1 8.2x10"' 8.210"7 70 1.610"7 .
to 19 .to 7.4x10"* to 7.4x10"* to 1.1x10"*
o Expoaurea resulting from use of akin lotlona aaaumlng ...
PCIla are preaenl In the surfactant at 25 mg/kg 6.4 2.5x10"* 2.5x10"* 70 1.1x10"*
o Expoaurea reaultlng from handling of printed matter
assuming PCbs ate present In the Ink pigment at . , '
25 mg/kg 5.9x10"^ 2.1x10"' 2.0x10"* 60 B.ttxlO'1
o Bxpoauceu raujiltlng from painting the Interior of
house aa lulling PCBa are preaont In the pigment at
25 mg/kg 7.0X10"1 2.7xlO'7 5.5xlO"B 14 2.4xlO"8
951 Upper
Confidence Urn
on
Exui-aa HUk
5.010"7
2.5x10"'
5.2x10"'
2.0xlO~*
6.0x10"] to
5.4xlO~*
1.8x10"*
1.4x10"'
4.0x10'"

-------