Neoplastic effects

Other papers in the Symposium deal with the antioxidant and hypolipidemic effects of IP6, its chelating effects in heavy metal toxicity, inhibition of renal stones and other beneficial effects such as inhibition of platelet aggregation, inhibition of inflammatory responses (Shamsuddin, 1998). The lipid lowering effect and anti-neoplastic effect of 1P6 were extensively reviewed (Jariwalla, 1999). Hence, 1P6 is a valuable component of rice bran in preventing disease and maintaining health. 1P6 is present at 1.8-2% in rice bran. 

Labors- Characteristics of administered material Age at time of admin. Number of animals Early effects (< 1 year) Late neoplastic effects (> 1 year) ... 

TABLE 9.4. Examples of Neoplastic Effects in Rodents with Limited Significance for Human Safety... 

As discussed in Section 2.6, chronic alcoholics receiving Antabuse (disulfiram) therapy are potentially more susceptible to toxic and neoplastic effects of 1,2-dibromoethane. It also follows that individuals with compromised liver or renal function or with asthma or other chronic respiratory diseases may have increased susceptibility to the toxic effects of 1,2-dibromoethane however, chemical-specific effects have not been identified. 

No neoplastic effect was observed in rats exposed to 0, 15, 45, or 135ppm for 6 hours/ day, 5 days/week for 2 years. Dose-related changes, which include atrophy of the neurogenic epithelial cells and hyperplasia of the reserve cells, mainly affected the anterior part of the olfactory epithelium. In the high-dose group there was opacity of the cornea. After a 6-month postexposure period reconstructive effects were observed in both tissues. 

TDLo/Toxic Dose Low—The lowest dose introduced by any route other than inhalation over any period of time that produces any toxic effect in humans or that produces carcinogenic, teratogenic, mutagenic, or neoplastic effects in humans and animals. 

The carcinogenicity of decaBDE was also evaluated in Sprague-Dawley rats (25/sex/dose) that were exposed to dietary doses of 0, 0.01, 0.1, or 1.0 mg/kg/day for approximately 2 years (702 days for males, 735 days for females) (Kociba et al. 1975 Norris et al. 1975b). The commercial mixture was comprised of 77.4% decaBDE, 21.8% nonaBDE, and 0.8% octaBDE and therefore differs from typical decaBDE formulations containing 97% decaBDE. Comprehensive histological examinations showed no exposure-related neoplastic effects. Tlie ability of this study to detect carcinogenic changes is limited by the very low dose levels in comparison to those tested in the NTP (1986) bioassay. 

In one study, reported as an abstract, in which rats were exposed to methyl acrylate by inhalation for two years, no neoplastic effect was reported (lARC, 1986). 

Ideally, future antineoplastic drug discovery should be based on a more rational, botanical, chemical, and pharmacological approach. A possible way to test the anti-neoplastic effects of compounds would be to use some semi in vitro-in vivo models. A more rational approach in antineoplastic research, combined with the enormous chemodiversity of flowering plants, will lead to the discovery of several molecules of clinical value. 

Since guanine aminohydrolase catalyzes the deamination of thioguanine and 8-azaguanine thereby destroying their anti-neoplastic effects, Baker and his colleagues have prepared a series of active site directed irreversible inhibitors to block the enzyme in tumor tissue (193). The most effective inhibitor, 9-(4-methoxy phenyl)guanine, effected a 50 inhibition at 0.38 nM in the presence of 13.3 juM substrate (194). 

Wattenberg, L.W., Jerina, D.M., Lam, L.K.T., and Yagi, H. Neoplastic Effects of Oral Administration of (+)-trans-7,8-dihydroxy-7,8-dihydroxy 7,8-dihydrobenzo(a)pyrene and their inhibition by butylated hydroxyanisole J Natl. Cancer Inst., 62 1103-1106, 1979. 

Jin Wong, H., Kyoungttwa, L. and Jim, E.S. (1 994) Anti neoplastic effects of extracts from tradition medicinal plants. Korean Journal of Pharmacognosy, 25, 1 71-1 77. 

Nishino, H., Tsushima, M., Matsuno, T., Tanaka, Y., Okuzmi, J., Murakoshi, M., Satomi, Y., Takayasu, J., Tokuda, H., Nishino, A., and Iwashima, A. 1992. Anti-neoplastic effect of halocynthiaxanthin, ametabolite of fucoxanthin. Anticancer Drugs, 3, 493 197. 

Chronic-Duration Exposure and Cancer. No information is available on the effects of chronic exposure to 1,1-dichloroethane in humans. The NCI study reported histopathological examinations for endpoints of systemic toxicity in addition to the neoplastic effects in rats and mice. No MRL can be derived for long-term exposure. Additional chronic toxicity studies particularly by the inhalation route would be useful to fully assess potential human health hazard from long-term exposure to... 

The European Commission Scientific Committee for Food in 1997 established 1% sodium saccharin in the diet as a clear no-observed-effect level (NOEL) in relation to male rat bladder tumors and for other non-neoplastic effects of saccharin. In response to primarily updated experimental data and the extensive epidemiological data with no evidence of any relationship between saccharin intake and bladder cancer in humans, the Committee set a full acceptable daily intake (ADI) for sodium saccharin of 0-5 mg kg body weight. If the ADIs were expressed in terms of the free acid, since sodium saccharin is not the only salt used, and taking into account of the molecular weight difference between sodium saccharin (molecular weight 241) and the free acid (molecular weight 183), then ADI expressed as the free acid is 0-3.8 mg kg body weight. 

Diethyltin-A-(2-pyridylmetylene)-4-toluidine dichloride was tested against P338 leukemia in mice and showed anti-neoplastic effects. This compound has induced significant delay in cell cycles in mouse bone marrow cells. 

Other non-neoplastic effects observed in the urinary system are inflammation and hyperplasia of the transitional epithelium of the kidney (rats) or bladder (rats and mice) following treatment with TBA [98]. These effects were observed in 13-week studies at 20 and 40 mg/ml in both sexes of both species. In the two-year studies with TBA, transitional cell hyperplasia was increased... 

CS2 was evaluated for carinogenicity in 2-year rodent bioassays. ° Compound-related non-neoplastic lesions of the respiratory tract were noted. Pathological changes observed in CS2-exposed rats included squamous metaplasia of the olfactory epithelium and hyperplasia and metaplasia of the respiratory epithelium hyperplasia and squamous metaplasia of the respiratory epithelium were observed in mice exposed to CS2. Neoplastic effects were not observed in either rats or mice exposed to test article. Conclusions drawn from these findings suggest that CS2 is non-carcinogenic for rats and mice. 

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