Neurobehavioral toxicity with low doses of sarin and soman.

The acute effects of single subtoxic doses (1/48-1/9 of LD50) of two potent organophosphates (OPs), sarin (12.5 and 50 micrograms/kg i.p.) and soman (4 and 20 micrograms/kg i.p.), were studied on behavior, motor performance and nociception in male Wistar rats. On the elevated plus-maze with two open + two closed arms, higher doses of soman and sarin decreased the proportion of entries made onto open arms (p less than 0.05), while the total number of entries onto open + closed arms was unchanged. On the narrow elevated horizontal bridge, the latencies to reach the safe platform were prolonged with the higher dose of sarin (p less than 0.05) but not with that of soman. On the broad and rod bridges, the latencies of OP-treated rats did not differ significantly from those of controls. OPs did not significantly impair either learning frequency in one-trial passive avoidance test, rotarod performance or nociception in hot plate test. The results suggest that in acutely nontoxic doses sarin and soman affect the behavior of rats, and that the action profiles of the OPs differ from each other. Both soman and sarin change the behavior of rats in the plus-maze test but only sarin seems likely to impair motor coordination/balance.

Assessment of acute behavioral toxicity of low doses of diisopropylfluorophosphate (DFP) in rats.

The effect on behavior of single subtoxic doses (100 and 600 micrograms/kg i.p., i.e. 1/77 and 1/13 of LD50, respectively) of an organophosphorous compound, diisopropylfluorophosphate (DFP), was studied in male Wistar rats. In the open-field test, the lower dose of DFP tended to increase ambulation, while the higher dose showed a trend towards a decrease in ambulation, rearing and frequency of defecation. In the elevated plus-maze, rotarod, elevated bridges and hot plate tests, DFP-treated rats did not differ significantly from the olive oil-treated controls. DFP significantly impaired the performance of rats in the one-trial passive avoidance task and dose-dependently decreased spontaneous locomotor activity for 4 hours after administration. At the doses used DFP only slightly inhibited acetylcholinesterase activity in the blood and different brain areas. The results show that the higher dose of DFP had an inactivating effect on the behavior of rats, while the lower dose did not markedly change their behavioral pattern. Our findings indicate that anticholinesterase compounds, such as DFP, can alter behavior even after single small subtoxic doses.

Acute neurobehavioural toxicity of trichothecene T-2 toxin in the rat.

The acute effects of single oral doses, 0.4 and 2.0 mg/kg, of trichothecene T-2 mycotoxin on behaviour, motor performance and nociception were studied in male Wistar rats. Both doses are sublethal and did not cause overt acute signs of intoxication. In the open field test, 2.0 mg/kg of T-2 toxin increased motionlessness and decreased sniffing (P less than 0.05) 4 hr after the administration. The higher dose shortened step-through latencies in the test trial of the 24-hr passive avoidance test (two-way shuttle box). The exponential data analysis showed that, in those rats that did not learn to avoid the dark (unsafe) compartment of the box, the retention after 2.0 mg/kg of T-2 toxin was only 25% of that in controls (P less than 0.001). T-2 toxin had no effect on motor coordination in the rotarod test and in the bridge walking test 7-8 hr after administration. T-2 toxin had no effect on nociception in the hot place test 8.5 hr after administration. The results suggest that T-2 toxin has some inactivating effects on behaviour of rats, and it seems to cause an impairment in the passive avoidance test at dose 2.0 mg/kg.

Acute neurobehavioural effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Han/Wistar rats.

The neurobehavioural effects of a single non-lethal dose (1000 micrograms/kg intraperitoneally) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were assessed in young male Han/Wistar rats, highly resistant to acute lethality of TCDD. TCDD decreased body weight significantly compared with ad libitum fed controls. TCDD did not change the behaviour or the motility of rats in the open field test 8 days after the treatment nor did it affect the spontaneous motor activity up to 27 days after the exposure. In the elevated plus-maze test for anxiety, TCDD-treated rats did not differ from either ad libitum fed controls or pair-fed controls. In the 24-hr passive avoidance test, the learning of TCDD-treated rats did not differ significantly from that of ad libitum fed controls or pair-fed controls from 8 hr to 16 days after the treatment. TCDD did not affect the motor coordination or the maintenance of balance on the rotating rod but it impaired them slightly in the elevated horizontal bridge test 16 hr after exposure. It did not affect nociception in the hot plate test 16 hr or 8 days after the injection. The results suggest that a single sublethal dose of TCDD does not alter markedly the general behaviour of Han/Wistar rats, in contrast to its striking effect on feeding behaviour which results in a marked decrease in body weight gain.