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Comparative toxicity of (+)‐(R)‐ and (−)‐(S)‐1,2‐dibromo‐3‐chloropropane
Author(s) -
Kouzi Samir A.,
Søderlund Erik J.,
Dybing Erik,
Meerman John H. N.,
Nelson Sidney D.
Publication year - 1995
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530070509
Subject(s) - chemistry , glutathione , toxicity , enantiomer , mutagen , stereochemistry , metabolism , biochemistry , carcinogen , in vivo , pharmacology , organic chemistry , enzyme , medicine , microbiology and biotechnology , biology
The haloalkane 1,2‐dibromo‐3‐chloropropane (DBCP), an environmental pollutant that was widely used as a soil fumigant, is a carcinogen and a mutagen and displays target‐organ toxicity to the testes and the kidneys. Because little is known about effects of stereochemistry on the metabolism and toxicity of halogenated alkyl compounds and because DBCP, which has a chiral center at C‐2, may show enantioselectivity in its metabolism and/or toxicities, the optically pure enantiomers of DBCP were tested in vivo in rats for organ toxicity as well as for bacterial mutagenicity. Organ toxicity studies showed that (S)‐DBCP was slightly more renal toxic than (R)‐DBCP but was not significantly more toxic than the racemate, and that no significant differences were observed in the extents of testicular necrosis and atrophy caused by either enantiomer or the racemate. In contrast, (R)‐DBCP was more mutagenic than either (S)‐DBCP or the racemate to Salmonella typhimurium (S. typhimurium) strains TA 100 and TA104. However, there was little or no enantioselectivity in glutathione S ‐transferase (GST)‐catalyzed conjugation reactions of glutathione with DBCP based on the lack of selectivity in the rates of disappearance of the enantiomers of DBCP in the presence of glutathione (GSH) and GSTs as monitored by chiral gas chromatography (GC). © 1995 Wiley‐Liss, Inc.