vexEPA
                                   United States
                                   Environmental Protection
                                   Agency
                                   Environmental Monitoring
                                   and Support Laboratory
                                   Las Vegas NE 89114
                                   Research and Development
                                   EPA-600/PS3-80-085   Sept. 1980
Project  Summary
                                   Biliary  Excretion  and  Tissue
                                   Distribution  of  Cadmium-109
                                   Administered  to  Rats
                                   A.A. Mullen and R.E. Mosley
                                     This report is part of a series of in-
                                   vestigations undertaken to establish
                                   the absorption/excretion  character-
                                   istics of various metal pollutants in
                                   order to provide information for selec-
                                   tion of  relatively rapid mammalian
                                   tests for estimating exposure.  This
                                   study  was  designed  specifically to
                                   ascertain the role of bile in the excre-
                                   tion of cadmium following oral or in-
                                   travenous administration of cadmium-
                                   109 to rats. Results of the study show
                                   that bile concentrates  cadmium and
                                   transports it into the gastrointestinal
                                   tract where it may be either reab-
                                   sorbed or excreted  in the feces.
                                     Tissue distribution of the  cadmium
                                   was also determined  in the study.
                                   Regardless of the route of administra-
                                   tion, the liver retained the highest cad-
                                   mium concentration, although kidney
                                   and bone also retained a large percen-
                                   tage of the administered radionuclide.
                                     This publication is a summary of the
                                   complete report, which can be pur-
                                   chased from the National Technical
                                   Information Service.

                                   Introduction
                                     Cadmium is present as a trace metal in
                                   the earth's crust and as an impurity in ores
                                   of other  metals. Concentration of ores
                                   and use of cadmium in  industrial pro-
                                   cesses  have  caused  cadmium to
                                   become  an  environmental  pollutant
                                   producing a variety of toxic effects.
                                     Because the body  appears to lack an
                                   effective mechanism for eliminating cad-
                                    mium,  cadmium  burden gradually in-
                                    creases with age. In addition, complex in-
                                    teractions that occur between cadmium
                                    and other divalent cations make predic-
                                    tions of intestinal absorption very dif-
                                    ficult.
                                     This study was undertaken to provide
                                    further information on the absorption, ex-
                                    cretion, and tissue distribution of cad-
                                    mium in the rat,  in an effort to select
                                    universally available biological monitors,
                                    and to provide a reliable method for quick-
                                    ly estimating potential exposure of critical
                                    segments of a population to a potentially
                                    hazardous pollutant.
                                    Results
                                     The difference in the excretion of cad-
                                    mium in urine and feces was measured in
                                    rats with either ligated or intact bile ducts.
                                    Three  days following  a  single  oral-
                                    administration  of  cadmium-109  plus
                                    stable cadmium chloride, 4 x 10  3 percent
                                    of the dose was excreted in the urine of
                                    rats with intact bile ducts, while 5 x 10  2
                                    percent was excreted in urine of rats with
                                    ligated bile ducts. While 82 percent of the
                                    dose was excreted via the feces of  intact
                                    rats, 71 percent was recovered in  feces
                                    from rats with ligated bile ducts. The
                                    amount of  the  dose recovered in tissue
                                    was 13 percent for intact rats and 30 per-
                                    cent for ligated rats.
                                     Following intravenous administration of
                                    cadmium, rats with intact bile  ducts ex-
                                    creted about 5 x 10-1 percent of the dose
                                    in urine versus 2 percent  for  rats with

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    Table 1.     Average Percent of Cadmium Dose Recovered Per Tissue
    Tissue
                                          Oral
                           Ligated
               Non-Ligated
                                                          Intravenous
Ligated
Non-Ligated
Liver
Spleen
Kidney
Heart
Brain
Skull
Bone*
1.86 + 0.89
4.65 ± 0.79 x 10-2
0.21 ± 0.08
3.20 ± 0.27 x 10-2
2.20 ± 0.24 x 10-2
4.36 + 0.93 x 10-2
4.23 ± 0.55 x 10-2
1.64 ± 0.67
4.49 ± 0.81 x 10-2
6.88 + 3.58 x 10-2
3.05 ± 0.40 x 10-2
2.01 ± 0.35 x 10-2
3.02 ± 1.01 x 10-2
1.90 ± 0.32 x 10-2
39.3 ± 14.8
4.37 ± 3.51 x 10-1
7.45 ± 1.95
2.96 ± 0.57 x 70-1
2.85 ± 0.76 x 10-2
4.20 ± 1.13x 70-i
2.82 ± 0.22
30.1 ± 10.4
4.60 ± 0.98 x 70-1
7.36 ± 4. 16
2.30 ± 7.52 x 70-1
2. 19 ± 1.50 x 70-i
2.09 ± 7.72x 70-1
3. 16 ± 0. 12
    ^Estimation based on percentage of body weight assigned to the bone of adult rats as reported by Sikor and Mahlum.
    ligated bile ducts. About 8 percent of the
    dose was excreted via the feces of rats
    with intact bile ducts,  compared to only
    about 6 x 10-1 percent by ligated  rats.
    The amount of the dose recovered in the
    tissues was 91 and 96 percent respectively
    for intact and ligated rats.
      As shown in Table 1, the liver, retaining
    the  highest concentration, appears to be
    the  organ of primary concern  in this
    study, although cadmium  was  also  re-
    tained in the kidneys and bone.

    Conclusions
      This investigation clearly demonstrated
    that bile plays and important role in the
    concentration and transport of cadmium
    for subsequent reabsorption or excretion.
    Collection of bile from animals endemic to
    a potentially polluted area would enable
    an investigator to easily determine an ear-
    ly increase in biologically available  cad-
    mium. However, caution must be exer-
    cised when attempting to correlate the
    amount of cadmium in the bile with the
          dose of cadmium received, as  dose
          threshold   effects  and  possible
          synergistic   reactions  with   other
          pollutants may affect the kinetics of bile
          production.
             Authors  are EPA employees  with the Environmental Monitoring Systems
               Laboratory, Las Vegas, NV (see below)
             The  complete report,  entitled "Biliary Excretion and Tissue Distribution of
               Cadmium-109 Administered to Rats," {Order No. PB 8021 7995; Cost: $5.00.
               subject to change) will be available from:
                     National Technical Information Service
                     5285 Port Royal Road
                     Springfield, VA 22161
                     Telephone: 703-487-4650
             EPA authors can be contacted at:
                     Environmental Monitoring Systems Laboratory
                     U.S. Environmental Protect/on Agency
                     Las Vegas, NV 89114
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
                           Postage and
                           Fees Paid
                           Environmental
                           Protection
                           Agency
                           EPA 335
Official Business
Penalty for Private Use $300
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