United States
                    Environmental Protection
                    Agency
Health Effects Research
Laboratory
Research Triangle Park NC 27711
                    Research and Development
EPA-600/S1-83-017 Jan. 1984
&EPA         Project  Summary
                    Inhalation  Teratology  Studies  of
                    Captan  and  Folpet  in  Mice

                    K. Diane Courtney, James E. Andrews, James T. Stevens, and Jackie D. Farmer
                      Timed pregnant  CD-1 mice were
                    exposed to  captan or folpet by  the
                    intragastric,  subcutaneous,   or
                    inhalation  route.   A  dose  of  100
                    mg/kg/day of  captan or folpet was
                    administered  subcutaneously  or
                    intragastrically from day 6 through  15
                    of gestation. The  dose  levels for the
                    inhalation route were averaged from
                    daily exposure  levels determined  by
                    monitoring the  chambers.  The
                    inhalation route  provided daily average
                    concentrations  approximating  491
                    mg/m3 for captan, and 624 mg/m3 for
                    folpet, four hr/day from the sixth to the
                    thirteenth day of gestation. The particle
                    size was less than 5//m. Approximately
                    10% maternal mortality was observed
                    with both captan  and  folpet by the
                    inhalation route, but no mortality was
                    seen by the other two routes. The only
                    fetal toxicity noted was a reduction in
                    fetal body weight in the group adminis-
                    tered captan subcutaneously. Neither
                    captan nor folpet  was teratogenic in
                    CD-1 mice exposed by the subcutane-
                    ous, oral or inhalation  routes.
                      This Project Summary was developed
                    by EPA's Health Effects Research Lab-
                    oratory. Research Triangle Park, NC, to
                    announce key findings of the research
                    project that is fully documented in a
                    separate report  of the same  title (see
                    Project Report ordering information at
                    back).

                    Introduction
                      Captan and folpet are fungicides with
                    structures  generally  similar  to
                    thalidomide,  which  raises  questions
                    about their teratogenic potential. Many
                    studies in the literature indicate that the
compounds are not teratogenic, whereas
some have found them to be teratogenic.
Thus, these fungicides were tested for
their teratogenic  potential  in mice by
using oral, subcutaneous, and inhalation
exposure routes.

Procedure
  Pregnant mice with known gestational
days were treated with captan and folpet
daily from gestational days 6 through 15
at a dose level of 100 mg/kg either by
gavage  or subcutaneous injection and
killed on day 17 An additional group of
mice was exposed to captan or folpet from
gestational days 6 through 13 and killed
on day 17.

Results and Discussion
  Neither  captan   nor folpet  was
teratogenic by oral, subcutaneous or
inhalation exposure routes. The exposure
levels of captan and folpet were maternally
lethal but did not affect the fetus.

Conclusion
  Captan and folpet atdosesof 100 mg/kg
administered  orally  or  subcutaneously
during  organogenesis  was  not
teratogenic  in  the  CD-1   mouse.
Inhalation exposure of CD-1 mice to cap-
tan or folpet at maternally lethal doses did
not  produce fetal malformations.

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      The EPA authors K. D. Courtney. J. E. Andrews, J. T. Stevens, and J. D. Farmer
       are with the Health Effects Research Laboratory, Research Triangle Park. NC
       27711.
      Diane Courtney is the EPA Project Officer (see below).
      The complete report, entitled "Inhalation Teratology Studies ofCaptan andFolpet
       in Mice," (Order No. PB 84-128 099; Cost: $7.00, subject to change) will be
       available only from:
             National Technical Information Service
             5285 Port Royal Road
             Springfield, VA 22161
             Telephone:  703-487-4650
      The EPA Project Officer can be contacted at:
             Health Effects Research Laboratory
             U.S. Environmental Protection Agency
             Research Triangle Park, NC 27711
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