Four groups of male Sprague-Dawley rats were given intraperitoneal (i.p.) injections. Group 1 was a control that received only saline. Group 2 received 40 mg/kg of 2-CAN. Group 3 received 100 mg/kg of 5-phenyl-1-pentyne (5P1P) an inhibitor of cytochrome P-450. Group 4 received 100 mg/kg of 5P1P one hour before 40 mg/kg of 2-CAN. Three hours following administration, the animals were euthanized via cardiac puncture. Cardiac blood was collected for cyanide and cyanate analysis. Liver and lung tissues were harvested and analyzed for glutathione. In a separate experiment, the time to onset of hind limb paralysis was measured in animals receiving 40 mg/kg 2-CAN and 100 mg/kg 5P1P one hour prior to 40 mg/kg 2-CAN.
Blood cyanide levels were increased in the 2-CAN group, but did not exceed 0.06 µg/mL, a concentration well below the minimum for producing adverse health effects. Compared to control animals, the 2-CAN treatment group had depleted glutathione by 20% in the lung and 44% in the liver. When 5P1P was administered prior to 2-CAN, there was no significant change in glutathione concentrations.
Plasma cyanate levels in the 2-CAN group were 436 nmol/L plasma, a 390% increase over control. When a 5P1P was administered prior to 2-CAN, cyanate levels were reduced by 55% to less than 195 nmol/L plasma. In addition to decreasing plasma cyanate levels, 5P1P 1 hour prior to 2-CAN delayed the onset of hind limb paralysis from 6 minutes to 16 minutes.
Since cyanide was not generated in substantial concentrations following 2-CAN administration, the use of an antidote specific for cyanide for 2-CAN toxicity may not be effective. The findings of increased cyanate levels in 2-CAN, combined with the hind-limb paralysis data suggest that cyanate, not cyanide, is the toxic metabolic product resulting from acute 2-CAN exposure.","abstract_html":"2-Chloroacrylonitrile (2-CAN) is a volatile, toxic chemical used as a raw material to manufacture pesticides. Although the toxic mechanism is not fully understood, the hypothesis in the literature is that 2-CAN may be metabolized to cyanide. An understanding of the mechanism of 2-CAN toxicity will permit more appropriate treatments in the event of an accidental exposure. </p><p> Four groups of male Sprague-Dawley rats were given intraperitoneal (i.p.) injections. Group 1 was a control that received only saline. Group 2 received 40 mg/kg of 2-CAN. Group 3 received 100 mg/kg of 5-phenyl-1-pentyne (5P1P) an inhibitor of cytochrome P-450. Group 4 received 100 mg/kg of 5P1P one hour before 40 mg/kg of 2-CAN. Three hours following administration, the animals were euthanized via cardiac puncture. Cardiac blood was collected for cyanide and cyanate analysis. Liver and lung tissues were harvested and analyzed for glutathione. In a separate experiment, the time to onset of hind limb paralysis was measured in animals receiving 40 mg/kg 2-CAN and 100 mg/kg 5P1P one hour prior to 40 mg/kg 2-CAN. </p><p> Blood cyanide levels were increased in the 2-CAN group, but did not exceed 0.06 µg/mL, a concentration well below the minimum for producing adverse health effects. Compared to control animals, the 2-CAN treatment group had depleted glutathione by 20% in the lung and 44% in the liver. When 5P1P was administered prior to 2-CAN, there was no significant change in glutathione concentrations. </p><p> Plasma cyanate levels in the 2-CAN group were 436 nmol/L plasma, a 390% increase over control. When a 5P1P was administered prior to 2-CAN, cyanate levels were reduced by 55% to less than 195 nmol/L plasma. In addition to decreasing plasma cyanate levels, 5P1P 1 hour prior to 2-CAN delayed the onset of hind limb paralysis from 6 minutes to 16 minutes. </p><p> Since cyanide was not generated in substantial concentrations following 2-CAN administration, the use of an antidote specific for cyanide for 2-CAN toxicity may not be effective. The findings of increased cyanate levels in 2-CAN, combined with the hind-limb paralysis data suggest that cyanate, not cyanide, is the toxic metabolic product resulting from acute 2-CAN exposure.","abstract_has_math":false,"creators":["Malichky, Paul"],"institution":null,"degree_name":"PhD","degree_level":"Immediate Access","degree_discipline":"Pharmacology-Toxicology","degree_department":null,"school":null,"contributors":["David Johnson","Paula Witt-Enderby","Frederick W Fochtman","Janet M Mostowy","J. Douglas Bricker","James K Drennen"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-01-01T08:00:00Z","date_published":"2011-01-01T08:00:00Z","updated_at":"2026-07-24T02:10:02Z","subjects":["2-Chloroacrylonitrile","Cyanate","Cyanide","Cytochrome P-450","Glutathione"],"languages":["English"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dsc.duq.edu/etd/860","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["David Johnson","Paula Witt-Enderby","Frederick W Fochtman","Janet M Mostowy","J. Douglas Bricker","James K Drennen"]},{"key":"dc:creator","label":"Author","values":["Malichky, Paul"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-03-28T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmacology-Toxicology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Immediate Access"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["2-Chloroacrylonitrile","Cyanate","Cyanide","Cytochrome P-450","Glutathione"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dsc.duq.edu/etd/860"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["2-Chloroacrylonitrile (2-CAN) is a volatile, toxic chemical used as a raw material to manufacture pesticides. Although the toxic mechanism is not fully understood, the hypothesis in the literature is that 2-CAN may be metabolized to cyanide. An understanding of the mechanism of 2-CAN toxicity will permit more appropriate treatments in the event of an accidental exposure.
Four groups of male Sprague-Dawley rats were given intraperitoneal (i.p.) injections. Group 1 was a control that received only saline. Group 2 received 40 mg/kg of 2-CAN. Group 3 received 100 mg/kg of 5-phenyl-1-pentyne (5P1P) an inhibitor of cytochrome P-450. Group 4 received 100 mg/kg of 5P1P one hour before 40 mg/kg of 2-CAN. Three hours following administration, the animals were euthanized via cardiac puncture. Cardiac blood was collected for cyanide and cyanate analysis. Liver and lung tissues were harvested and analyzed for glutathione. In a separate experiment, the time to onset of hind limb paralysis was measured in animals receiving 40 mg/kg 2-CAN and 100 mg/kg 5P1P one hour prior to 40 mg/kg 2-CAN.
Blood cyanide levels were increased in the 2-CAN group, but did not exceed 0.06 µg/mL, a concentration well below the minimum for producing adverse health effects. Compared to control animals, the 2-CAN treatment group had depleted glutathione by 20% in the lung and 44% in the liver. When 5P1P was administered prior to 2-CAN, there was no significant change in glutathione concentrations.
Plasma cyanate levels in the 2-CAN group were 436 nmol/L plasma, a 390% increase over control. When a 5P1P was administered prior to 2-CAN, cyanate levels were reduced by 55% to less than 195 nmol/L plasma. In addition to decreasing plasma cyanate levels, 5P1P 1 hour prior to 2-CAN delayed the onset of hind limb paralysis from 6 minutes to 16 minutes.
Since cyanide was not generated in substantial concentrations following 2-CAN administration, the use of an antidote specific for cyanide for 2-CAN toxicity may not be effective. The findings of increased cyanate levels in 2-CAN, combined with the hind-limb paralysis data suggest that cyanate, not cyanide, is the toxic metabolic product resulting from acute 2-CAN exposure."]},{"key":"dc:title","label":"Title","values":["Cyanate Formation Following 2-Chloroacrylonitrile Exposure and the Role of Cytochrome P-450"]}]}],"canonical_facts":{"dc:contributor":["David Johnson","Paula Witt-Enderby","Frederick W Fochtman","Janet M Mostowy","J. Douglas Bricker","James K Drennen"],"dc:creator":["Malichky, Paul"],"dc:date.available":["2018-03-28T07:00:00Z"],"dc:description.abstract":["2-Chloroacrylonitrile (2-CAN) is a volatile, toxic chemical used as a raw material to manufacture pesticides. Although the toxic mechanism is not fully understood, the hypothesis in the literature is that 2-CAN may be metabolized to cyanide. An understanding of the mechanism of 2-CAN toxicity will permit more appropriate treatments in the event of an accidental exposure.
Four groups of male Sprague-Dawley rats were given intraperitoneal (i.p.) injections. Group 1 was a control that received only saline. Group 2 received 40 mg/kg of 2-CAN. Group 3 received 100 mg/kg of 5-phenyl-1-pentyne (5P1P) an inhibitor of cytochrome P-450. Group 4 received 100 mg/kg of 5P1P one hour before 40 mg/kg of 2-CAN. Three hours following administration, the animals were euthanized via cardiac puncture. Cardiac blood was collected for cyanide and cyanate analysis. Liver and lung tissues were harvested and analyzed for glutathione. In a separate experiment, the time to onset of hind limb paralysis was measured in animals receiving 40 mg/kg 2-CAN and 100 mg/kg 5P1P one hour prior to 40 mg/kg 2-CAN.
Blood cyanide levels were increased in the 2-CAN group, but did not exceed 0.06 µg/mL, a concentration well below the minimum for producing adverse health effects. Compared to control animals, the 2-CAN treatment group had depleted glutathione by 20% in the lung and 44% in the liver. When 5P1P was administered prior to 2-CAN, there was no significant change in glutathione concentrations.
Plasma cyanate levels in the 2-CAN group were 436 nmol/L plasma, a 390% increase over control. When a 5P1P was administered prior to 2-CAN, cyanate levels were reduced by 55% to less than 195 nmol/L plasma. In addition to decreasing plasma cyanate levels, 5P1P 1 hour prior to 2-CAN delayed the onset of hind limb paralysis from 6 minutes to 16 minutes.
Since cyanide was not generated in substantial concentrations following 2-CAN administration, the use of an antidote specific for cyanide for 2-CAN toxicity may not be effective. The findings of increased cyanate levels in 2-CAN, combined with the hind-limb paralysis data suggest that cyanate, not cyanide, is the toxic metabolic product resulting from acute 2-CAN exposure."],"dc:identifier":["https://dsc.duq.edu/etd/860"],"dc:language":["English"],"dc:subject":["2-Chloroacrylonitrile","Cyanate","Cyanide","Cytochrome P-450","Glutathione"],"dc:title":["Cyanate Formation Following 2-Chloroacrylonitrile Exposure and the Role of Cytochrome P-450"],"thesis:degree_discipline":["Pharmacology-Toxicology"],"thesis:degree_level":["Immediate Access"],"thesis:degree_name":["PhD"]},"updated_at":"2026-07-24T02:10:02Z"}