Differentiation of the mechanisms of oncogenicity of 1,4-dioxane and 1,3-hexachlorobutadiene in the rat
HERO ID
4158030
Reference Type
Technical Report
Year
1989
Language
English
| HERO ID | 4158030 |
|---|---|
| Year | 1989 |
| Title | Differentiation of the mechanisms of oncogenicity of 1,4-dioxane and 1,3-hexachlorobutadiene in the rat |
| Authoring Organization | Dow Chemical Company |
| Publisher Text | Dow Chemical Company |
| City | Midland, MI |
| Abstract | l,4-Dioxane (DX) and 1.3-hexachlorobutadiene (HCSD) were studied relative to their probable mechanisms of tumorigenicity in male SpragueDawley rats. Upon repeated exposure of rats to tumorigenic dosage levels of OX (1000 mg/kg/day for 11 weeks via drinking water) or HCBD (20 mg/kg/day for 3 weeks orally), histological and biochemical evidence of cellular toxicity was observed in their respective target organs, liver (DX) and kidney (HCBD). These observations correlate well with the chronic bioassays indicating that tumorigenicity was associated only at dose levels which were cytotoxic. This implies that tissue injury (cytotoxicity) rnay contribute to the carcinogenic process. While no genetic effects were observed in the liver with dioxane, some genetic damage (DNA repair) and slight alkylation of kidney DNA was observed in rats dosed with 20 mg HCBD/kg. Thus the lack of any significant genetic acting potential for dioxane suggests that dioxane may cause tumors via a nongenetic mechanism, possibly through repeated tissue injury and/or the enhancement of the expression of pre-existing oncogenic factors through a phenobarbital-like enzyme induction. While HCBD appears to cause tumors, also primarily via a nongenetic mechanism probably by repeated tissue injury at high dosages, a minor genetic contribution to the carcinogenic effect of HCBD cannot be ruled out at this time. |
| Report Number | OTS: OTS0000719; 8EHQ Num: FYI-OTS-1089-0719; DCN: NA; TSCATS RefID: 404730 |
| Is Certified Translation | No |
| Dupe Override | No |
| Number Of Pages | 28 |
| Comments | ICF NOTE: |
| Is Public | No |
| Language Text | English |
| Relationship(s) |