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Acrylonitrile Pharmacodynamics and Mutagenesis.

PB88246947

Publication Date	1979
Personal Author	Wolff, M. S.
Page Count	10
Abstract	A study was made of the pharmacokinetics of acrylonitrile (107131) (AN) with emphasis on routes of elimination and mechanisms of metabolism. Rats were given intraperitoneal injections of AN at 5 to 60mg/kg. Two AN analogues, crotononitrile (4786203) (CN) and methacrylonitrile (126987) (MN), were also studied. CN and MN concentrations in blood followed a first order kinetic elimination. AN demonstrated a biphasic kinetic elimination. AN was measurable in fat, liver and blood for 18 hours after a 37mg/kg dose. Fecal excretion was significant at levels of 3 to 9 parts per million (ppm) at 3 hours after exposure. Urine levels of 0.03ppm were registered after 5.3mg/kg dose levels and 0.1ppm after 81mg/kg. Total AN in feces, urine and tissues even at very short intervals after intraperitoneal administration represented only 3 to 30 percent of the administered dose. The fast AN metabolic pathway was consistent with Michael addition to AN or its analogs and would readily account for cyanide formation.
Keywords	Acrylonitriles Methacrylonitrile Laboratory animals Metabolism Nitriles Excretion Liver Crotononitrile Toxic substances Tissue distribution Pharmacokinetics Adipose tissue
Source Agency	National Institute for Occupational Safety and Health
NTIS Subject Category	57Q - Pharmacology & Pharmacological Chemistry 57Y - Toxicology
Corporate Authors	Mount Sinai School of Medicine, New York. Environmental Sciences Lab.; National Inst. for Occupational Safety and Health, Cincinnati, OH.
Supplemental Notes	Sponsored by National Inst. for Occupational Safety and Health, Cincinnati, OH.
Document Type	Technical Report
Title Note	Rept. for 1 Jul 77-30 Jun 79,
NTIS Issue Number	198823

Acrylonitrile Pharmacodynamics and Mutagenesis.

Acrylonitrile Pharmacodynamics and Mutagenesis.
PB88246947

Publication Date	1979
Personal Author	Wolff, M. S.
Page Count	10
Abstract	A study was made of the pharmacokinetics of acrylonitrile (107131) (AN) with emphasis on routes of elimination and mechanisms of metabolism. Rats were given intraperitoneal injections of AN at 5 to 60mg/kg. Two AN analogues, crotononitrile (4786203) (CN) and methacrylonitrile (126987) (MN), were also studied. CN and MN concentrations in blood followed a first order kinetic elimination. AN demonstrated a biphasic kinetic elimination. AN was measurable in fat, liver and blood for 18 hours after a 37mg/kg dose. Fecal excretion was significant at levels of 3 to 9 parts per million (ppm) at 3 hours after exposure. Urine levels of 0.03ppm were registered after 5.3mg/kg dose levels and 0.1ppm after 81mg/kg. Total AN in feces, urine and tissues even at very short intervals after intraperitoneal administration represented only 3 to 30 percent of the administered dose. The fast AN metabolic pathway was consistent with Michael addition to AN or its analogs and would readily account for cyanide formation.
Keywords	Acrylonitriles Methacrylonitrile Laboratory animals Metabolism Nitriles Excretion Liver Crotononitrile Toxic substances Tissue distribution Pharmacokinetics Adipose tissue
Source Agency	National Institute for Occupational Safety and Health
NTIS Subject Category	57Q - Pharmacology & Pharmacological Chemistry 57Y - Toxicology
Corporate Authors	Mount Sinai School of Medicine, New York. Environmental Sciences Lab.; National Inst. for Occupational Safety and Health, Cincinnati, OH.
Supplemental Notes	Sponsored by National Inst. for Occupational Safety and Health, Cincinnati, OH.
Document Type	Technical Report
Title Note	Rept. for 1 Jul 77-30 Jun 79,
NTIS Issue Number	198823