Dose response of sulphur mustard: behavioral and toxic signs in rats.

The present study elucidates the behavioral and toxic signs in rats following dermal application of sulphur mustard (SM). Graded doses of SM (0.10, 0.25, 0.50, 0.75 and 1.0 LD50) were topically applied to male Wister rats. The body weight as well as behavioral/toxic signs and symptoms were recorded at 1, 2, 3, and 4th day after application of SM. Sulphur mustard consistently decreased body weights of rats in a dose and time dependent manner with maximum decrease on 3rd day post treatment. Sedation and diarrhea were significant in response to doses of SM intoxication in rats. It is concluded that the body weight, sedation and diarrhea may be used as a reliable parameter in evaluating SM intoxication. It is also suggested that hydration and hypertonic saline must be used as a rescue agent within 1-3 days after exposure to SM.

A comparative study of delayed neurotoxicity in hens following repeated administration of organophosphorus compounds.

Hens treated with Mipafox (10 mg/kg, sc), sarin (50 micrograms/kg, sc) or parathion (1 mg/kg, sc) daily for 10 days exhibited severe, moderate and no ataxia respectively on 14th day after the start of exposure. The neurotoxic esterase (NTE) activity was significantly inhibited in the brain, spinal cord and platelets of hens treated with mipafox or sarin whereas no change was noticed with parathion treatment. All three compounds significantly inhibited acetylcholinesterase (AChE) activity in the platelets. Spinal cord of hens treated with mipafox, sarin or parathion showed axonal degeneration heavy, moderate and none respectively. It is concluded that repeated administration of equitoxic doses of mipafox, sarin and parathion to hens are marked, moderate and non-delayed neurotoxic respectively.

Influence of pretreatment of carbamates on dynamic pulmonary mechanics in rats exposed to sarin aerosols.

The effect of pretreatment of two carbamates, pyridostigmine and physostigmine on dynamic pulmonary mechanics has been studied in rats exposed to sarin aerosols. Sign-free dose of pyridostigmine (0.075 mg/kg, i.m.) or physostigmine (0.1 mg/kg, i.m.) did not significantly alter the parameters of the dynamic pulmonary mechanics 20 min after treatment. However, sarin (51.2 mg/m3, for 15 min) depressed the respiratory rate, air flow and minute volume and enhanced the transthoracic pressure and tidal volume. Pretreatment with carbamates 20 min prior to sarin exposure significantly modified or counteracted the above induced changes. It is concluded that the protective effect of carbamates is mainly due to the correction of respiratory changes caused by sarin aerosols in rats.

Effects of topically applied sulphur mustard on tissue glycogen, blood glucose, lactate and pyruvate in mice.

Bis-2-Chloroethyl sulphide, commonly known as sulphur mustard (SM) or mustard gas, an alkylating agent, is frequently used as a chemical warfare agent. Inhibition of glycolysis has been related to skin injury and cell death. The effects of SM on tissue glycogen, blood glucose, lactate/pyruvate ratio were investigated in the present study. After a single dermal application of 1.0 LD50 SM in mice, a significant hyperglycemia was observed at 24 hr post exposure. There was a corresponding decrease in liver glycogen content, with no alteration in glycogen content of brain, muscles and kidney. Blood pyruvate and lactate levels were not appreciably altered.

Biochemical and pathological changes in response to hyperoxia and protection by antioxidants in rats.

A significant decrease in blood haemoglobin, reduced glutathione and protein in lung and liver, without any change in blood reduced glutathione, was observed in rats exposed to 80% oxygen. Hydrogen peroxide induced erythrocyte haemolysis was significantly increased following exposure to hyperoxia. The lungs of rats exposed to hyperoxia showed perivascular edema. Simultaneous treatment with antioxidants, vitamin A, C, or E, protected the animals against oxygen toxicity.

A comparative study of biochemical changes induced by inhalation of aerosols of o-Chloroacetophenone & Dibenz (b,f)-1,4-oxazepine in rats.

The biochemical changes in blood samples of rats at different intervals after O-Chloroacetophenone (CN) and Dibenz (b,f)-1,4 oxazepine (CR) were studied. After a single subacute (1/10 LC50) exposure, both the compounds induced hyperglycaemia which was abolished within 24 h. The level of plasma urea was unaltered. CR exposed animals did not show any significant changes in plasma GOT, acid and alkaline phosphatase activities at different intervals. However, in CN exposed animals, a significant elevation of the activities of GOT, GPT, acid and alkaline phosphatase was observed at different intervals. All the parameters became normal within seven days after the exposure. Inhalation of CN aerosols can thus lead to tissue damaging effects in rats.

DFP induced changes in acetylcholinesterase activity and glycogen level in certain brain regions of mice.

DFP in acute dose (2 mg/kg i. p.) in mice significantly inhibited acetylcholinesterase AChE) activity in five regions of brain i.e. cerebral cortex, corpus striatum, medulla, cerebellum and hypothalamus. The inhibition was accompanied by depletion of glycogen from these regions 1 hr after DFP administration. The inhibition of enzyme activity was more in corpus striatum and medulla and glycogen depletion was more in cerebral cortex in comparison to other regions of the brain. These changes may be due to stimulatory effect of DFP on these regions of brain in mice.

Distribution of neurotoxic esterase in certain brain regions of laboratory animals.

Certain organophosphorous compounds caused the inhibition of 'neurotoxic esterase' present in central nervous system. The role of this enzyme is different from that of cholinesterase. The level of neurotoxic esterase in brain, corpus striatum and spinal cord of rats, mice, guineapigs and hens was measured. Maximum level of the enzyme was found in hens, followed by guineapigs, rats and mice in the order. The concentration of the enzyme was higher in corpus striatum greater than whole brain greater than spinal cord. The determination of the normal level of neurotoxic esterase may be useful in monitoring the exposure to organophosphorous compounds.