Metabolic Fate of P,p'-ddt (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane)in Rats.

* Inquiries regarding this paper should be addressed to M. S. Dunn, University of California, Los Angeles. The experimental data are from a dissertation submitted by Joseph D. Pinto to the Graduate School of the University of California, Los Angeles, in partial fulfillment of the requirements for the degree of Doctor of Philosophy. The chemical names and structures for DDT and its derivatives, referred to by key letter designations in the text, are shown in Scheme 1. This work was supported by Grants GM-05574, B-1665, and AM 08523.01 from the United States Public Health Service. t Present address, Division of Biochemistry, University of Illinois, Urbana, Illinois. $ Present address, Department of Research, Mount Sinai Hospital, Los Angeles, California 90048. 1 The abbreviations used are: DDT or p,p’-DDT, l,l, l-trichloro-2,2-bis (p-chlorophenyl)ethane; DDE or p, p’-DDE, 1, ldichloro-2-bis(p-chlorophenyl)ethylene; DDA or p,p’-DDA, bis(p-chlorophenyl)acetic acid; DBM, p,p’-dichlorodiphenylmethane; DBP, p,p’-dichlorobenzophenone; DBH, p,p’-dichlorobenahydrol; TNB, tetranitrobenzophenone. presented data suggesting that the major fecal products consist. of DDA conjugated with either cholanic acid or amino acids. DDA and DDE were not isolated as crystalline products; however, their presence in the feces was inferred (4) from the behavior of these compounds on a modified Davidow column (5) and on a modified Mosbach (6) partition column. Only one metabolite of p ,p’-DDT, namely p ,p’-DDA, has been identified in the urine of rabbits, rats, and man (7-9), although the presence of two unidentified metabolites has been reported in the urine of rabbits which have ingested p , p’-DDT (7). It was suggested (7) that the unidentified metabolites were conjugates of p , p’-DDA, since nitration of either p,p’-DDA or either of the metabolites yielded an identical tetranitrodichlorobenzophenone.2 The neutral product, DDD, has been identified as a DDT metabolite in the body fat of rats which have ingested p,p’-DDT (10). The present study was undertaken to gain additional information concerning the identity of DDT metabolites produced in the rat. Fractionation of urine and feces from rats fed p,p’-DDT yielded crystalline p ,p’-DDA and gave evidence for the presence of several amino acid conjugates of p,p’-DDA. Fractionation of feces from rats fed p,p’-DDA yielded a homogeneous acidic metabolite identified as a conjugate of p,p’-DDA with aspartic acid and serine, and produced evidence for the presence of four neutral metabolites, possibly identical with DBM, DBP, DBH, and DDE, respectively.