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Metabolism and disposition of hexachloro( 1,3)butadiene in rats
METMOLIS~ AND DISPOSITION OF HEXACHMR0(1,3)BUTADIENE
IN BATS
IlBICHLBT,
D. IWSTITUPE OF PHwuco MGY AND TOXICOLOGY OF THE UNIVERSITY, VBRSIUCHEW STRA88W 9, D-0700 WttRZBURG,FRG. Ierachloro(l,3)butadiene (HCBD) is a stable environmental contaminant which occurs a8 a by-product in the aynthesee of tri- and tetrachloroethylene. HCBD ia one of the few chlorinated aliphatic hydrocarbons exhibiting severe acute nephrotoxic propertiasr in addition, it produces adenocarcinomas of the kidney. Phamacokinetics or biochemical mechanieme which could explain thie dietlnct organotrrJpiem are unknown at present. In an attempt to answer thie question, the fate of [14-ClHCBD in rate after eingle oral doses was etudied. Z&haled air, urine and feces were collected for 72 h following administration of 1 and 50 w/kat 42 I or. reev., 69 6 of the radloactivitv were found in the feces, 3O.~~B-&nd 11 8 in urk. In exhaled air, unchanged [14-CJHCBD (5.3 # and 5.4 6) and IlIlCO? (3.6 6 and 1.2 %) were found, Covalent binding proved to be higheac 15 the kidney with 0.53 nmoles/mg protein (6 h after gavage, dose 1 mg/kg); it increased very significantly (1.16 niwlee/mg protein) when phenobarbital was preadminietered, and decreased (0.14 nmoles/mg protein) when piperonyl butoxide was given. In the urine, 10 non-volatile metabolitee were isolated. Two major metabolltes were identified by GWlS as pentachloro-derivatives: one was identified as pentachlorobutenic acid. The results support the formation of a monoewxide be the firat step in HCBD metabolism a&l-a subsequent migration of the double bond, which contributes to a chemical stabilization of the molecule. Supported by the Deutsche Porechungegemeinechaft
EPOXYDE RESINS : ELECTROPHILIC, ItlMUNOPATHOCENICAND CARCINOGENIC SUBSTANCES. CLINICAL
CERUAIS P.,
DALLY S.,
FBIJRNIER E.,
AND EXPERIMENTAL ASPECTS.
EFTHYHIOU H-L.,
CHA.BAUXC.
The authors present their clinical and experimental studies since 1963 cutaneous accideots in workers having a prolonged contact with epoxyde resins and their associated coapounds. Clinically these accidents consist not only in allergic contact dermatitis but also bullous eruptions. Their experimental studies realized by guinea-pig sensibilization confirm the highly immunopathogenic role of epoxydes. A detailed clinical history of s multiple squamous cell carcinoma occuring in a worker who hsd suffered through several years of contlct eczema to epoxyde resins is presented. The authors then cite the experi8entsl studies which attribute mutagenic and carcinogenic roles to certain epoxyde resins widely utilized in industry ; they underline the neceesity to pursue the fundamental (aetructure-biological activity" relationships) and +@idemiological investigations in ithisdomain. Utilization precautions must be confirmed se of nor particularly with workers who seem to manipulate epoxyde resins without contact dermatitis. The structural relationships between carcinogenic and inmunopsthogenic
on
chemical
elements
end compounds
ere
emphasized.
IN BATS
IlBICHLBT,
D. IWSTITUPE OF PHwuco MGY AND TOXICOLOGY OF THE UNIVERSITY, VBRSIUCHEW STRA88W 9, D-0700 WttRZBURG,FRG. Ierachloro(l,3)butadiene (HCBD) is a stable environmental contaminant which occurs a8 a by-product in the aynthesee of tri- and tetrachloroethylene. HCBD ia one of the few chlorinated aliphatic hydrocarbons exhibiting severe acute nephrotoxic propertiasr in addition, it produces adenocarcinomas of the kidney. Phamacokinetics or biochemical mechanieme which could explain thie dietlnct organotrrJpiem are unknown at present. In an attempt to answer thie question, the fate of [14-ClHCBD in rate after eingle oral doses was etudied. Z&haled air, urine and feces were collected for 72 h following administration of 1 and 50 w/kat 42 I or. reev., 69 6 of the radloactivitv were found in the feces, 3O.~~B-&nd 11 8 in urk. In exhaled air, unchanged [14-CJHCBD (5.3 # and 5.4 6) and IlIlCO? (3.6 6 and 1.2 %) were found, Covalent binding proved to be higheac 15 the kidney with 0.53 nmoles/mg protein (6 h after gavage, dose 1 mg/kg); it increased very significantly (1.16 niwlee/mg protein) when phenobarbital was preadminietered, and decreased (0.14 nmoles/mg protein) when piperonyl butoxide was given. In the urine, 10 non-volatile metabolitee were isolated. Two major metabolltes were identified by GWlS as pentachloro-derivatives: one was identified as pentachlorobutenic acid. The results support the formation of a monoewxide be the firat step in HCBD metabolism a&l-a subsequent migration of the double bond, which contributes to a chemical stabilization of the molecule. Supported by the Deutsche Porechungegemeinechaft
EPOXYDE RESINS : ELECTROPHILIC, ItlMUNOPATHOCENICAND CARCINOGENIC SUBSTANCES. CLINICAL
CERUAIS P.,
DALLY S.,
FBIJRNIER E.,
AND EXPERIMENTAL ASPECTS.
EFTHYHIOU H-L.,
CHA.BAUXC.
The authors present their clinical and experimental studies since 1963 cutaneous accideots in workers having a prolonged contact with epoxyde resins and their associated coapounds. Clinically these accidents consist not only in allergic contact dermatitis but also bullous eruptions. Their experimental studies realized by guinea-pig sensibilization confirm the highly immunopathogenic role of epoxydes. A detailed clinical history of s multiple squamous cell carcinoma occuring in a worker who hsd suffered through several years of contlct eczema to epoxyde resins is presented. The authors then cite the experi8entsl studies which attribute mutagenic and carcinogenic roles to certain epoxyde resins widely utilized in industry ; they underline the neceesity to pursue the fundamental (aetructure-biological activity" relationships) and +@idemiological investigations in ithisdomain. Utilization precautions must be confirmed se of nor particularly with workers who seem to manipulate epoxyde resins without contact dermatitis. The structural relationships between carcinogenic and inmunopsthogenic
on
chemical
elements
end compounds
ere
emphasized.