38 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS hydrophilic analogue would be a still more effective preservative for currently fashionable cosmetics and toiletries. APPENDIX The effects of methyl, ethyl and propyl parabens on the growth rate constant of Escherichia co/i as reported by Lang and Rye (10) can be represented as: k = -- as) where k ø is the rate constant in the absence of preservatives and s, is the saturation fraction of any one of the parabens. The dimensionless empirical constant a has the value of 2.0 from the data reported (k = 0 at s, • 0.5). For small values of the microbial volume (v in eq 4), s, is approximately the apparent saturation fraction in the uncontaminated product but for large values of v corresponding to large inocula or long incubation times, si is diminished according to eq 4 and k may then tend to return to k ø. Since we assume that the parabens partition equally and reversibly into live and dead organisms, the dependence of the growth rate constant on time will depend on the inhibition mechanism invoked, whether by killing or by increasing the vegetative period. If a killing mechanism is operative, the cell volume, v, is not given by a count of recoverable viable organisms but it might be given by a measure of absorbance or turbidity if these methods respond to both dead and viable cells. In any case, it appears that eq 5 gives only the capacity for reduction of the initial value of the growth rate constant if this is greater than zero, the total cell volume increases without limit and any finite amount of preservative will eventually be overwhelmed (assuming, of course, that growth is not limited by exhaustion of nutrients or other external factors). In this sense, the non-zero capacity values given in Table I are fictitious. The capacity then, appears to be rigorously definable only for high preservative levels which monotonically reduce the count of viable organisms. It also appears that there are intermediate preservative levels which will cause a temporary reduction in viable count followed by resumption of growth. REFERENCES (1) T. R. Aalto, M. C. Firman and N. E. Riglet, p-Hydroxybenzoic acid esters as preservatives, J. Am. Pharm. Assoc., 42, 44½-457 (1953). (2) E. Boehm and E. Jones, Nipa-ester combinations as preservatives and antisepncs, J. Soc. Coo met. Chem., 8, 30-40 (1957). (3) E. Boehm, Combination of the esters of para-hydroxybenzoic acid, Amer. Per., 73, 57--38 (1959). (4) It. N. Gerrard, M. S. Parker and K. Bullock, The fungistatic activity of methyl and propylhydroxy- benzoates and a mixture of these against penicil[ium spinulosum, J. Pharm. Pharmac., 14, 105-107 (•962). (5) O. M. Littleiohn and W. J. Husa, The potentizing effect of antimolding agents in syrups, J. Am. Pharm. Assoc., 44, 305-308 (1955). (6) J. Schimmel and W.J. Husa, The effect of various preservatives on microorganisms isolated from deteriorated syrups,J. Am. Pharm. Assoc., 45,204-208 (1956). (7) J. Ferguson, The use of chemical potentials as indices of toxicity, Proc. Roy. Soc. Lond, Sect B 127, 587-404 (1959).

PARABENS 39 (8) W. P. Evans, Applicability of the Ferguson principle to systems of mixed preservatives, J. Pharm. Pharmaco/., 17,217-221 (1965). (9) A. Albert, "Selective Toxicity," -3rd Ed.,John Wiley & Sons Inc.: New York, N.Y., 1965 pp 328-335. (10) M. Lang and R. M. Rye, The uptake by Escherichia co/i and growth inhibitory properties of methyl, ethyl and propyl p-hydroxybenzoates,J. Pharm. Pharmac., 24, 160P-161P (1972). (11) J. J. O'Neill, P. L. Peelor, A. F. Peterson and C. H. Strube, Application of the Ferguson principle to the selection of sparingly soluble preservatives, in "Developments in Industrial Microbiology," Society for Industrial Microbilogy: Arlington, Va., 1978 Vol. 19, pp 335-345. (12) A. G. Mitchell, Bactericidal activity of chloroxylenol in aqueous solutions of cetomacrogol, J. Pharm. Pharmaco/., 16, 533-537 (1964). (13) P. B. Chemburkar and R. S. Joslin, Effect of flavoring oils on preservative concentrations in oral liquid dosage forms,J. Pharm. Sci., 64, 414-417 (1975).