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.
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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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