JUL -3
                         TSCR  SECTION 8(E)

                        QUESTIONS  & ANSWERS
 Q..   Does Section 8(e) of TSCA intend the submission of animal test
 information:  (a)  when a  determination  of  "substantial risk" has
 been  made,  or (b)  where merely a finding of positive animal test
 results  useful  in the further assessment  of  human risk has been
 determined?

      A.   TSCA Section 8(e) requires the timely submission of
      evidence (including preliminary evidence)  from animal
      studies  that  implicates  the tested chemical as causing
      serious toxicologic effects  (e.g., cancer, neurotoxicity,
      birth defects).  A  decision to report the observance of
      such serious  toxicological  effects should not hinge in
      any way  on a judgement of either the actual or potential
      exposure to the chemical or a judgement about the degree
      of relevancy of the findings to an  overall assessment of
      human risk.  In other words, the decision to report under
      Section  8(e) in such cases should be based simply on the
      observance of the serious toxicologic effects.


Q.    What criteria should be used to determine if the results from
cancer bioassay studies in animals should be submitted to EPA under
Section 8(e)? For example, when should animal  studies showing only
a significant increase in benign tumors over controls be submitted?

      A.   Reporting of benign and/or malignant tumors should
      take place,  for example, when  either statistically or
      biologically  significant increases  over controls are
      observed.  The observation of such  increases are made in
     many cases  at  interim sacrifices  performed  typically
     during long term exposure studies  in animals.
                                                i

Q.   How should  reproductive  or developmental toxicity  data be
evaluated for possible TSCA Section  8(e)  submission if maternal
toxicity is also present?                       ,

     A.   Statistically or biologically  significant increases
     in teratogenic effects' or other serious embryotoxic or
     fetotoxic effects  (e.g.,  significant embryo  or  fetal
     lethality,  spontaneous abortion) should be reported under
     Section 8(e) regardless of the level of maternal toxicity
     observed in the study. .

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 Q.   What criteria should be used  to determine which reproductive/
 developmental effects observed in. animal tests are reportable under
 Section 8(e)?  For example, should developmental effects that are
 reversible, such as reduced birth  weight and/or incomplete ossifi-
 cation, trigger reporting?

      A.   In addition to'teratogenic effects, serious adverse
      developmental effects (e.g.,  significant embryo or fetal
      lethality,  significantly reduced fetal/birth  weights,
      significantly retarded/incomplete skeletal ossification)
      should be reported.  In addition,  serious adverse effects
      on the male/female reproductive system (e.g., significant
      testicular  or ovarian  atrophy,  significantly  reduced
      fertility, sterility) should  be  reported.


 Q.    What criteria should be used  in determining if the results of
 acute  toxicity studies  constitute information  that  reasonably
 supports a conclusion of substantial  risk?

      A.   Criteria used to  determine  Section 8(e)  reporting
      in the  case of  acute/subacute  toxicity findings  will
      depend on the nature of the effects observed and the dose
      at which the effects occurred.  For example,  information
      that shows a tested chemical to be extremely toxic (e.g.,
      causes lethality at  very low doses)  by,  for  example,
      inhalation,  dermal  application  or oral administration
      should be reported.  On the other hand,  the reporting of
      information  showing a  chemical  to be moderately  toxic
      will depend on the degree of actual or potential exposure
      to the tested  chemical.   Information showing a chemical
      to be  slightly or minimally toxic on an acute/subacute
      basis  is not considered typically to be  reportable.   In
      addition to  extreme  toxicity,  certain  other  serious
      toxicological  effects  (e.g.,  neurotoxicity,   adverse
      reproductive system effects) seen  in an-acute or subacute
      animal study should  be reported under Section  8(e).


Q.   When evaluating subchronic studies in animals,  what  criteria
should be used to determine reportability of adverse effects?  For
example, should increased or decreased organ(s) size in the absence
of histopathological changes be reported?

     A.   Serious toxic  effects (e.g.,  neurotoxic  effects,
     serious reproductive system effects)  observed during the
     conduct of subchronic  studies  should be reported.  This
     includes  readily  observable serious  effects or  serious
     effects seen only as the resu-lt  of gross and/or histo-
     pathological examination.  As  is the case for  acute  and
     subacute  toxicity studies,  the degree  of  the  observed
     toxicity is important.  The more serious  (or significant)
     the observed  effect,  the less heavily one should consider
     actual/potential exposure for  reporting and vice versa.

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Q.   What criteria constitute evidence of renor+-aHi~ «    *.  •  •




     A.    Typically,  neurotoxic effects  that are observed i

     bv1™ ?omS1S arS ?°^'  in  and of themselves,  cSnsTS
     by  EPA to be reportable under Section  8(e)  of TSCA
     many cases,  however, already reportable data

     £Si™^ 2 K hlg,hly tOXic (lethal>  substances
     accompanied by information  concerning observed neurotoxll
     etfects.  m short or long  term exposure studies in which
     serious neurotoxic signs and symptoms (e.g.,  convulsions

     dvSrSnctlon^T' m°t0r dvsfun^ion,  narcosis  SeSaviorli
     dysfunction)  are  seen in non-moribund  animals, however
     pllce    rep°rtln9 of the n^rotoxic effects Should
    ™« fSri,°US ^  *^ genot°xicological  effects  (e.g.,
    tKLSL   °m
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