Chlorinated Cyclodiene Insecticide Research Articles

Hydroxylation and epoxidation of chlordene by the mixed-function oxidase of the tropical and cold fresh water fish

1. Hydroxylation and epoxidation of the chlorinated cyclodiene insecticide, chlordene, by the hepatic mixed-function oxidase occur maximally at 37°C in the tropical fish, the Kissing Gourami, Helostoma sp., and at 26δC in the cold water fish, the Bluegill, Lepomis macrochirus. 2. The optimum pH for these reactions is 7·6 in the Kissing Gourami and 7·4 in the Bluegill and the Lake Trout, Salvelinus fontinalis. 3. The mixed-function oxidase of the Bluegill is 4 times more active in hydroxylating than in epoxidizing chlordene. 4. This system in the Kissing Gourami and the Lake Trout shows low rates of hydroxylation and epoxidation which are similar to the epoxidation level seen with the Bluegill. 5. The Kissing Gourami produce a third metabolite, 1-hydroxyl-2,3-epoxychlordene. 6. The time-course sequence of these reactions is hydroxylation-, epoxidation-, epoxide-hydroxide formation, indicating that different sites of the enzyme may be involved in these reactions.

Mixed-function oxidase activity toward cyclodiene insecticides in bass and bluegill sunfish

Microsomal mixed-function oxidase (MFO) was characterized in liver of freshwater fishes, bass, Micropterus dolomeiux, and bluegill, Lepomis macrochirus, using the chlorinated cyclodiene insecticide aldrin as a substrate. The MFO activity of bluegill adults, bluegill fry, and bass fry using cyclodienes as substrates was compared with that of mouse. Aldrin epoxidase activity was found to be high in bluegill fry (73% of the activity in mouse) compared to bluegill adults (13% of the activity in mouse). Chlordene was found to be metabolized by both fish and mouse MFO to chlordene 2,3-epoxide and 1-hydroxychlordene. Competitive inhibition between various cyclodiene substrates studied in mouse and fish showed that endrin was a potent inhibitor of aldrin epoxidation in vitro.

Toxicity-metabolism relationship of the photoisomers of certain chlorinated cyclodiene insecticide chemicals.

Photoaldrin, photodieldrin, and photoheptachlor are more toxic than their corresponding parent compounds (aldrin, dieldrin, and heptachlor) to freshwater invertebrates and vertebrates, and to adult houseflies. The increase in toxicity is very significant in the case of the amphipod,Gammarus (1.5–12 times), bluegill fry (3.6–5.7 times), mosquito larvae,Aedas (2.3–6 times), minnow fry (2.5 times), and the isopid,Asellus (2 times). The greatest increases occur with photodieldrin which is 12 and 5 times more toxic than dieldrin, respectively, toGammarus, and to blue-gill fry, and with photoaldrin which is 6 and 4 times more toxic than aldrin, respectively, to mosquito larvae and bluegill fry. The toxicities of the photoisomers of isodrin and chlordene are generally less than those of their parent compounds to all the organisms tested. The basis of the differences in toxicities of the chlorinated cyclodiene photoisomers appears to be related to their chemical structure which possibly affects their action at the site(s) of toxic action and/or detoxication. The acidic proton present at the secondary chloride in photoaldrin, photodieldrin, and photoheptachlor possibly is responsible for the formation of charge-transfer complexes between components of the nerve and the mixed-function oxidase; the latter enzyme apparently dehydrochlorinates these photo products to their corresponding, more toxic ketones. The absence of such protons in photoisodrin and photochlordene renders them incapable of forming such ketones. The inhibition of these reactions by sesamex in house flies increases the stability of the chlorinated cyclodiene insecticides and, thus, significantly affects their toxicity. The conversion of photoaldrin, photodieldrin, and photoheptachlor to more-toxic and lipophilic ketones warrants additional studies of their accumulation and subsequent concentration by the food chain.

Relationship between serum enzymes and histological changes in liver after administration of heptachlor in the rat

Investigations described previously / 5 / showed that after a single dose as well as during the longtime administration of heptachlor, a chlorinated cyclodiene insecticide, increased glutamic-pyruvic transaminase and aldolase in the serum of rats. The conclusion was drawn that an increase of activity in these enzymes may represent a suitable criterion for the evaluation of acute and subacute effects of h e p t a c h l o r . I t has a l s o been shown / 1 , 4 / t h a t some c h l o r i n a t e d i n s e c t i c i d e s cause p a t h o l o g i c a l t e r a t i o n s i n t h e l i v e r o f e x p e r i m e n t a l a n i m a l s . T h e r e f o r e t h e main o b j e c t i v e o f t h i s s t u d y was to d e t e r m i n e the r e l a t i o n s h i p be tween i n c r e a s e i n t h e serum enzyme a c t i v i t y , d e s c r i b e d above~ and h i s t o l o g i c a l changes in l i v e r f o l l o w i n g a d m i n i s t r a t i o n o f h e p t a c h l o r . S p e c i f i c a l l y , and f rom a t h e r a p e u t i c and p r e v e n t i v e a s p e c t , i n f o r m a t i o n i s n e e d e d c o n c e r n i n g the t ime c o u r s e o f t h e s e a l t e r a t i o n s .