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Studies on the tumor initiation/promotion potential of six middle distillates (MDs) in mouse skin
H Jungen1, W Mellert, R Wenzel-Hartung
1DGMK German Society for Petroleum Sciences and Coal Chemistry, Hamburg, Germany.
Abstract:
Six middle distillates (MDs) were tested for tumor initiating/promoting activity after application to the skin of 30 male CD-1 (ICR) BR mice per group. As the control, 7,12-dimethylbenz[a]-anthracene (DMBA) was used for initiation followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) for promotion. For assessing the tumor-initiating activity, 50 microliters of neat MDs was administered for 5 days with subsequent TPA promotion. In the promotion bioassay, after DMBA initiation 50 microliters of the neat MDs was administered twice weekly until Week 28. For the examination of complete carcinogenic activity, one MD was given without DMBA initiation. Hyperkeratosis, hyperplasia, and dermal inflammation, occurring during the initiation with the MDs, were completely reversible during the 2-week treatment-free period after initiation. Similar skin findings were observed during promotion with the MDs. Regarding the number of affected animals and the severity of the response, TPA was more irritating than the MDs. The initiation study revealed skin tumors for the DMBA/TPA control (30/30), MD 57,389 (14/30), MD 57,396 (5/30), MD 57,383 (4/30) and MD 57,324 (2/30). The promotion study revealed tumor induction by MDs 57,389 (9/30), 57,324 (1/30), 57,393 (1/30), and 57,396 (1/30). Two of 30 animals treated with MD 57,389 developed tumors without DMBA initiation thus indicating that it also is a complete carcinogen. MD 57,399 caused neither initiating nor promoting effects. The tumors observed were diagnosed histopathologically predominantly as squamous cell papillomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Middle distillates (MDs) were evaluated for carcinogenic activity. MD 57,389 showed significant tumor-initiating and promoting effects, and also acted as a complete carcinogen.
Area of Science:
- Toxicology
- Dermatology
- Carcinogenesis
Background:
- Middle distillates (MDs) are complex mixtures requiring toxicological assessment.
- Understanding the tumor-initiating and promoting potential of MDs is crucial for risk evaluation.
Purpose of the Study:
- To evaluate the tumor-initiating, promoting, and complete carcinogenic activity of six middle distillates.
- To compare the irritant effects of MDs with known carcinogens 7,12-dimethylbenz[a]-anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA).
Main Methods:
- A multi-stage skin carcinogenesis bioassay was performed on male CD-1 (ICR) BR mice.
- Tumor initiation involved topical application of MDs followed by TPA promotion.
- Promotion assays involved DMBA initiation followed by MD application.
- Complete carcinogenicity was assessed by applying one MD without prior initiation.
Main Results:
- MD 57,389 demonstrated significant tumor initiation (14/30 mice) and promotion (9/30 mice).
- Two mice treated with MD 57,389 alone developed tumors, indicating complete carcinogenicity.
- Other MDs showed varying degrees of initiating or promoting activity, with MD 57,399 showing no effects.
- TPA exhibited greater irritancy than the tested MDs.
Conclusions:
- MD 57,389 possesses tumor-initiating, promoting, and complete carcinogenic properties.
- The study highlights the need for careful evaluation of middle distillates for potential health risks.
- Histopathological analysis predominantly identified squamous cell papillomas as the observed tumors.