CASTOR OIL

    Explanation

         Castor oil is obtained from the seeds of the castor bean plant
    (Ricinus communis L., Euphorbiaceae). The oil consists of a
    triglyceride of fatty acids. The fatty acid content of castor oil
    consists of about 88-90% ricinoleic acid, 4-5% linoleic acid, 2-3%
    oleic acid, 1% palmitic acid, 1% stearic acid, about 1%
    dihydroxystearic acid, and trace amounts of other fatty acids (Binder
    et al. 1962).

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         About 7% of the ricinoleic acid present in a 1 ml oral dose of
    castor oil given by stomach tube to fasted Sprague-Dawley rats was
    absorbed into the chyle within a 24-hour period. About 24% of the
    ricinoleic acid was absorbed if the substance was given to fed rats.
    Seven weanling rats were given a diet containing 20% castor oil, the
    animals gained weight on the diet, although at a lower rate than
    animals fed an olive oil supplemented diet. After eight weeks on the
    castor oil diet, the amount of ricinoleic acid in the animals' fat
    pads was about 9.7%. When animals were fed the castor oil diet for
    four weeks then switched to an olive oil diet for 14 days, the amount
    of ricinoleic acid in the fat pads decreased to about 2% (Watson &
    Gordon, 1962).

         Studies in humans indicated that the percentage absorption of
    castor oil is inversely proportional to the dose given. A dose of 4 g
    of castor oil was almost completely absorbed; whereas, 64% of a dose
    of 50 g appeared in the faeces within 24 hours, and almost 90% of 60 g
    dose was excreted in the faeces. Doses of 10 g or more of castor oil
    produced either mild laxation of purgation (Watson et al., 1963).

    TOXICOLOGICAL STUDIES

    Special studies on cytotoxicity

         Ricinoleic acid was cytotoxic in vitro to isolated intestinal
    epithelial cells from hamsters as based on release of radiolabelled
    chromium, inhibition of 3-O-methylglucose transport and failure to
    exclude trypan blue. The cytotoxicity began to occur at ricinoleic
    acid concentrations greater than about 0.1 mM (Caginella et al.,
    1977).

    Special studies on intestinal histology

         No microscopic changes were noted in the villus architecture of
    the small intestine of random bred white mice following daily oral
    dosing with 0.3 ml per day of castor oil for 12 weeks (Gibbins & John,
    1970).

         Substantial architectural changes were seen upon light or
    electron microscopic examination of the mucosal cells of hamster small
    intestine perfused in vivo in the presence of 8 mM sodium
    ricinoleate. After treatment, the villus tips were capped with
    vaccuolated epithelial cells with disintegrating brush borders; the
    tight junctions were, however, not altered. Ricinoleate treatment was
    accompanied by increased mucosal cell exfoliation as evidenced by
    appearance of DNA in the perfusate. Membrane damage was accompanied by
    increased sucrase activity and appearance of phospholipid in cell-free
    aliquots of luminal fluid. There was also an increased clearance of
    inulin and a 16 000 molecular weight dextran (Cline et al., 1976).

         Dose-related epithelial damage and increased mucosal permeability
    was seen upon perfusion of rabbit colon in vivo with 0, 2.5, 5.0,
    7.5 and 10.0 mM concentrations of ricinoleate. Only occasional focal
    epithelial damage was seen with 2.5 mM ricinoleate. Severe damage
    was seen at 7.5 and 10.0 mM ricinoleate. There were also large dose-
    related increases in the plasma to lumen clearances of urea and
    creatinine (Gaginella et al., 1976).

    Special studies on the incorporation of ricinoleic acid into phospholipids

         Adult rats were fed for 25-40 days on a diet containing 48%
    castor oil. Judging from the absence of hydroxy fatty acids, none of
    the ricinoleic acid from the castor oil was incorporated into the
    phospholipids of the liver, skeletal muscle, and small intestine. The
    animals did not eat during the first few days of the experiment and
    weight loss occurred. Aversion to the diet was soon overcome and in
    most cases the initial body weight was restored. At no time during the
    experiment was there any evidence of cartharsis (Steward & Sinclair,
    1945).

    Special studies on gastrointestinal motility and water absorption

         Sodium ricinoleate at 2 mM concentration caused a 48% reduction
    in net water absorption in vitro by isolated segments of hamster
    jejunum. The substance also caused a significant decrease in sodium
    and chloride absorption, but not potassium absorption (Stewart et al.,
    1975a).

         In vivo studies carried out with dogs indicated that 45 ml of
    castor oil given by stomach tube decreased the activity of circular
    smooth muscle in the intestine (Stewart et al., 1975a).

         Ricinoleic acid depressed the spontaneous or induced contractile
    activity of smooth muscle preparations from rat colon, rabbit jejunum
    and guinea-pig taenia coli and ileum (Stewart et al. 1975b).

         Studies with perfused human subjects showed that ricinoleic acid
    caused a decrease in water absorption by the ileum at intraluminal
    concentrations of 0.5 mM or higher. Concentrations of about 2 mM
    or higher caused net secretion of water in the jejunum. Ricinoleic

    acid was absorbed at about half the rate of oleic acid by the perfused
    subjects (Ammon et al. 1974).

    Acute toxicity

         No data available.

    Short-term studies

         No data available.

    Long-term studies

         No data available.

    Comments

         At low doses castor oil is readily absorbed by man. As the oral
    dose increases, per cent. absorption decreases and laxation occurs.

         Castor oil has a long history of use as a laxative and aside from
    these effects it has been used apparently without harm. At laxation
    levels castor oil might be expected to inhibit the absorption of fat
    soluble nutrients, notably vitamins A and D. Therefore, food additive
    use of castor oil should be kept well below levels where absorption
    would be inhibited. At doses of 4 g in adults absorption appears to be
    complete and may be considered as a no-effect level.

         However in light of the lack of adequate long-term studies of
    immediate relevance the Committee applied a more conservative margin
    of safety.

    EVALUATION

    Level causing no toxicological effect

    Man: 70 mg/kg bw.

    Estimate of acceptable daily intake for man

    0-0.7 mg/kg bw.

    REFERENCES

    Ammon, H. V., Thomas, P. J. & Phillips, S. F. (1974) J. Clin.
         Invest., 53, 374

    Binder, R. G. et al. (1962) J. Amer. Oil Chem. Soc., 39, 513

    Cline, W. S. et al. (1976) J. Clin. Invest., 58, 380

    Gaginella, T. S. et al. (1976) Clin. Res., 24, 534A

    Gaginella, T. S. et al. (1977) J. Pharmacol. exp. Ther., 201, 259

    Gibbins, R. L. & John, T. J. (1971) J. Path., 103, 57

    Stewart, J. J. et al. (1975a) J. Pharmacol. exp. Ther., 192, 458

    Stewart, J. J., Gaginella, T. S. & Bass, P. (1975b) J. Pharmacol. exp.
         Ther., 195, 347

    Stewart, W. C. & Sinclair, R. G. (1945) Arch. Biochem., 8, 7

    Watson, W. C. & Gordon, R. S. (1962) Biochem. Pharmacol., 11, 229

    Watson, W. C. et al. (1963) J. Pharm. Pharmacol., 15, 183
    

    See Also:
       Toxicological Abbreviations
       Castor oil (ICSC)
       CASTOR OIL (JECFA Evaluation)