Detail of "56856-83-8"

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Natural history of intestinal neoplasms induced in rats by a single injection of methyl(acetoxymethyl)nitrosamine

Natural history of intestinal neoplasms induced in rats by a single injection of methyl(acetoxymethyl)nitrosamine. Ward, Jerrold M.; Rice, Jerry M.; Roller, Peter P.; Wenk, Martin L. (Natl. Cancer Inst., Bethesda, Md., USA). Cancer Res., 37(9), 3046-52 (English) 1977. CODEN: CNREA8. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Section cross-reference(s): 14 Male Sprague-Dawley-derived rats (Charles River CD) were injected once i.p. at 5 weeks of age with methyl(acetoxymethyl)nitrosamine [56856-83-8] at a dose level of 0.1 mmol/kg (one-half of the 50% lethal dose). Groups of 27 to 30 rats were sacrificed 20, 25, 30, 40, and 50 weeks later to study the development and natural history of induced tumors of the intestines. An addnl. 30 rats were allowed to die or were killed in poor condition. From 70 to 90% of the rats developed tumors from 20 to 50 weeks after injection, and 70 to 86% of the rats had intestinal tumors, most commonly in the small intestine. Most tumors of the small intestine were tubular adenocarcinomas that progressively invaded the gut wall. Tumor size correlated with degree of invasion of extramucosal tissues. As they grew large, these tumors developed cystic spaces and foci of stromal osteoid metaplasia. Such cystadenocarcinomas rarely metastasized despite their large size. Stormal lymphoid reaction was frequently obsd. Four of 14 mucinous (signet ring) adenocarcinomas originating in the small intestine metastasized to the peritoneal cavity. Colon tumors occurred more variably in 6 to 42% of rats in differnt groups and were usually polypoid adenocarcinomas that never invaded the tunica muscularis. Only a few invasive tubular adenocarcinomas were seen. The carcinogen also induced other tumors in the peritoneal cavity and abdominal viscera in low incidence, including sarcomas, mesotheliomas, lymphangiomas, renal tumors, carcinomas of the seminal vesicles, and, occasionally, tumors of other tissues.

Interference of acetoxyalkylnitrosamines with limb bud differentiation in organ culture

Interference of acetoxyalkylnitrosamines with limb bud differentiation in organ culture. Stahlmann, Ralf; Bluth, Ursula; Wiessler, Manfred; Neubert, Diether (Inst. Toxikol. Embryopharmakol., Freie Univ. Berlin, Berlin D-1000, Fed. Rep. Ger.). Arch. Toxicol., 54(2), 109-29 (English) 1983. CODEN: ARTODN. ISSN: 0340-5761. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Eight N-nitrosamines monosubstituted at the a-C with an acetoxy group were tested for their teratogenic potential in a mouse limb bud culture system. The following results were obtained: N-methyl-N-(a-acetoxy)methylnitrosamine (I) [56856-83-8]-a deriv. of dimethylnitrosamine-was the strongest teratogen in this group of chems. N-tert-Butyl-N-(a-acetoxy)methylnitrosamine [53198-38-2]-releasing a carbonium ion of low chem. reactivity-possessed the lowest activity. The primary a-acetates with unbranched side chains [N-propyl-N-(a-acetoxy)methylnitrosamine [66017-91-2] or N-butyl-N-(a-acetoxy)methylnitrosamine [56986-36-8]] were more active than the corresponding derivs. with branched side chains. The secondary a-acetate [N-ethyl-N-(a-acetoxy)ethylnitrosamine [58431-24-6]] was clearly less active than the primary a-acetate, N-ethyl-N-(a-acetoxy)methylnitrosamine [65986-80-3]. A teratogenic potential could also be demonstrated in the organ culture system with the cyclic deriv. N-nitroso-(a-acetoxy)pyrrolidine [59435-85-7]. With the use of limb buds from 12-day-old mouse embryos, the explants showed the highest susceptibility to the teratogens on the 1st day of culture. No effect could be produced if the substances were added to the culture medium at the 3rd day of culture or later. When initiating the culture with limb buds from 11-day-old mouse embryos, the concns. needed to induce typical effects were lower than those tested with 12-day-old explants.In this article, certain chemicals are used. Some of their cas registry numbers are 53198-38-2 and 56986-36-8 Typical and pronounced impairment with morphogenetic differentiation could be induced by I if the substance was present in the medium for <60 min - the shortest period tested was 15 min. A different abnormality pattern could be induced with the various substances tested. This may partly be explained by a quite different stability of the compds. in the test system. Thus, N-nitrosamines must be expected to be highly teratogenic if they can be activated in embryonic tissues. Such an activation into potent electrophilic agents does not occur in rodents under normal conditions. .