首页   按字顺浏览 期刊浏览 卷期浏览 Teratogenic and antiteratogenic effects of nicotinamide derivatives in chick embryos
Teratogenic and antiteratogenic effects of nicotinamide derivatives in chick embryos

 

作者: EdwinM. Uyeki,   John Doull,   C. C. Cheng,   Miwa Misawa,  

 

期刊: Journal of Toxicology and Environmental Health  (Taylor Available online 1982)
卷期: Volume 9, issue 5-6  

页码: 963-973

 

ISSN:0098-4108

 

年代: 1982

 

DOI:10.1080/15287398209530218

 

出版商: Taylor & Francis Group

 

数据来源: Taylor

 

摘要:

Teratogenic and antiteratogenic effects of nine nicotinamide analogs in chick embryos were investigated. Further, the teratisms of 6‐aminonicotinamide (6‐AN), nicotinamide analogs, and an organophosphate (diazinon) were compared. White leghorn chick embryos were used. Agents were injected into the yolk of eggs on d 3 of incubation. Morphological observations were made on d 17 of incubation. Chemical names for compounds I to IX are: I, 6‐dimethylaminonicotinamide; II, 6‐diethylaminonico‐tinamide; III, 6‐methylamino‐3‐(N‐methyl)‐nicotinamide; IV, 6‐dimethylamino‐3‐pyrimidine carboximide; V, 6‐(dimethylamino)‐nicotinic acid; VI, 6‐chloro‐3‐[N‐(5‐diethylamino)‐2‐pentyl]‐nicotinamide; VII, 6‐mercaptonicotinamide; VIII, [N‐acetyl‐N'‐(3‐pyridyl)‐carbonyl]‐hydrazine; IX, nicotinamide 1‐N‐oxide. The LD50 values in μmol per egg were as follows: 6‐AN, 0.073; compound II, 0.23; compound III, 1.11; compound I, 1.32; compound VI, about 3. Compounds IV, V, VII, VIII, and IX showed no toxicity or lethality at the highest doses tested (10 μmol/egg). Among the nine nicotinamide analogs, compounds I, II, and III, which have an amino group at the 6‐position of the pyridine ring, were teratogenic. Their teratogenic signs were similar to those caused by 6‐AN: they showed growth retardation, anteriorly directed short legs, and coarse, dense feathering. The teratogenic effects of compounds I, II, and III were prevented by pretreatment with nicotinamide, as were the effects of 6‐AN and diazinon. Among the nine analogs, only compound VIII had an antiteratogenic effect against the diazinon‐induced micromelia (in which the cardinal signs were tibiotarsal anguiations and poor feathering). For teratisms produced by 6‐aminonicotinamide analogs and organophosphates, nicotinamide was an effective antiteratogenic agent. However, some differences in the malformations induced by both types of agents were found. We suggest that the addition of a 3‐acetylpyridine type to the nicotinamide‐related teratisms (6‐AN type, 3‐acetylpyridine type, and organophosphate type) will provide a clearer distinction among the types.

 

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