Effect of bromine and chlorine positioning in the induction of renal and testicular toxicity by halogenated propanes
Lag, M; Soderlund, EJ; Omichinski, JG; Brunborg, G; Holme, JA; Dahl, JE; Nelson, SD; Dybing, E
HERO ID
2300279
Reference Type
Journal Article
Year
1991
Language
English
PMID
| HERO ID | 2300279 |
|---|---|
| In Press | No |
| Year | 1991 |
| Title | Effect of bromine and chlorine positioning in the induction of renal and testicular toxicity by halogenated propanes |
| Authors | Lag, M; Soderlund, EJ; Omichinski, JG; Brunborg, G; Holme, JA; Dahl, JE; Nelson, SD; Dybing, E |
| Journal | Chemical Research in Toxicology |
| Volume | 4 |
| Issue | 5 |
| Page Numbers | 528-534 |
| Abstract | A series of halogenated propanes were studied for renal and testicular necrogenic effects in the rat and correlated to their ability to induce in vivo renal and testicular DNA damage and in vitro testicular DNA damage. l,2-Dibromo-3-chloropropane (DBCP) and 1,2,3-tribromo-propane were most potent in causing organ damage in both kidney and testes. Extensive necrosis was evident at 85 /μmol/kg in kidney and at 170 μmol/kg in testis. The dibromomonochlorinated analogue l,3-dibromo-2-chloropropane was less organ toxic than DBCP and 1,2,3-tribromo-propane, but induced more organ damage than the dichloromonobrominated analogues 1-bromo-2,3-dichloropropane and l,3-dichloro-2-bromopropane. Dihalogenated propanes were even less necrogenic. These observed differences in toxic potency between the halogenated propanes could not be explained by relative differences in tissue concentrations. The ability of the halogenated propanes to induce DNA damage in vivo correlated well with their ability to induce organ damage. However, DNA damage occurred at lower doses and at a shorter period of exposure than organ necrosis. This indicates that DNA damage might be an initial event in the development of organ necrosis by halogenated propanes in general. Further, testicular DNA damage induced by the halogenated propanes in vivo correlated well with the DNA damage observed in isolated testicular cells in vitro, showing that toxicity was due to in situ activation. The numbers, positions, and the types of halogen substituents appear to be important determinants in causing DNA damage and necrogenic effects. The toxic potential of the halogenated propanes was in the following order: 1,2,3-tribromopropane > l,2-dibromo-3-chloropropane >l,3-dibromo-2-chloropropane > l,3-dichloro-2-bromopropane a; l-bromo-2,3-dichloropropane> 1,2,3-trichloropropane =* 1,2-dibromopropane > 1,3-dibromopropane > l-bromo-3-chloro-propane. The most toxic analogues contain three halogens with at least two vicinal bromines. |
| Doi | 10.1021/tx00023a007 |
| Pmid | 1793801 |
| Wosid | WOS:A1991GG36300007 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | ProQuest URL: https://www.proquest.com/scholarly-journals/effect-bromine-chlorine-positioning-induction/docview/72674373/se-2?accountid=171501 |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
|