Signs of toxicity

HYDANTOINS Fhenytoin is the most commonly prescribed anticonvulsant because of its effectiveness and relatively low toxicity. However, a genetically linked inability to metabolize phenytoin has been identified. For this reason, it is important to monitor serum concentrations of the drug on a regular basis to detect signs of toxicity Fhenytoin is administered orally and parenterally. If the drug is administered parenterally, the IV route is preferred over the intramuscular route because erratic absorption of phenytoin causes pain and muscle damage at the injection site... 

The nurse monitors vital signs every 4 hours or as ordered. Any adverse drug reactions or signs of toxicity are reported to the primary health care provider immediately. 

Chitosan acetate and lactate salt films have been tested as wound-healing materials. Mechanical, bioadhesive and biological evaluation of the films were carried out. The results were compared to Omiderm . Chitosan lactate exhibited a lower tensile strength, however, it was more flexible and bioadhesive than chitosan acetate. Chitosan lactate and Omiderm did not cause any allergic reactions in contrast, chitosan acetate produced skin irritation clearly due to the anion. Nevertheless, no sign of toxicity was encountered when the extracts of three preparations were administered parenterally [244]. 

Male rats exposed to 264 mg/m of methyl parathion by inhalation had 59% (range 53-61%) inhibition of blood (a combination of erythrocyte and plasma) cholinesterase 1 hour after exposure (EPA 1978e). These animals had typical cholinergic signs of toxicity salivation, exophthalmos, laerimation, spontaneous defecation and urination, and muscle fasciculation. Values for controls were not provided. Death was not correlated to the degree of eholinesterase inhibition in whole blood. 

Similar results for rats were reported by Crowder et al. (1980). Oral administration of 1 mg/kg/day of methyl parathion (99.9% purity) in com oil on days 7-15 of gestation resulted in increased mortality in pups, relative to controls. Significant difference from controls in a maze transfer test was observed in pups from the treated group. However, use of a single-dose level precluded the assessment of dose-response, and several other behavioral end points were not affected. Furthermore, no information was presented regarding body weights or signs of toxicity in the treated dams. 

Cimetidine, an H2 antagonist used therapeutically in patients with ulcers, inhibits activity of hepatic microsomal enzymes. When rats or mice were pretreated with cimetidine, dose-related lethality of methyl parathion was reduced, and cholinergic signs of toxicity were delayed. Simultaneous administration with methyl parathion did not reduce toxicity (Joshi and Thornburg 1986). 

Immunotoxicity. Limited information is available regarding the effects of endosulfan on the human immune system. However, specially designed studies using rats indicate that both humoral and cellular immune responses are depressed by ingested endosulfan at doses that do not induce any overt signs of toxicity (Banerjee and Hussain 1986,1987). In vitro studies support the possibility that endosulfan affects immune system function (Das et al. 1988). These results demonstrate that immunotoxicity may be a more sensitive end point of endosulfan-induced toxicity than other end points, and humans may be at risk for adverse immune effects following exposure to endosulfan. An intermediate-duration oral MRL was derived based on the observation of depressed immune responses (Banerjee and Hussain 1987). 

Parenteral lethality was determined by injecting rabbits of mixed sexes intraperitoneally with 31.6, 63, 126, 252, and 500 /xg/kg of 2,3,7,8-TCDD as a 0.01% corn oil suspension control rabbits were injected with corn oil. The rabbits were housed in individual holding cages and were observed for signs of toxicity for four weeks. The LDso s were calculated by the Weil modification of the Thompson method 14, 15) or by the Litchfield and Wilcoxon method (9). The acute lethality studies were terminated when it was evident that the survivors were not showing signs of toxicity. 

While all species lost body weight following treatment with 2,3,7,8-TCDD, other signs of toxicity were species dependent. Ascites was seen in mice. Anorexia, dehydration, depression, emaciation, intestinal hemorrhage, and alopecia were seen in dogs. Certain rabbits treated intra-peritoneally with 2,3,7,8-TCDD developed skin lesions typical of those associated with acnegens. 

Discovery of Poisoning by Fresh Water Algal Blooms and Signs of Toxicity... 

Perform pharmacokinetic adjustments as necessary. Recommend a monitoring plan for the antibiotic course. Are any other laboratory tests necessary Are signs of toxicity present ... 

In a 90-day toxicity study in which 179 mice received diisopropyl methylphosphonate in the diet at doses of 0, 27, 91, or 273 mg/kg/day, two deaths occurred in the 91 mg/kg/day male group. Since no deaths were observed in the 273-mg/kg/day group and no other signs of toxicity were observed, it was concluded that there was no evidence of toxicity in this 90-day study (Hart 1976). Four male rats died (1 control, 1 low-dose, and 2 high-dose animals) out of a total of 256 animals in a 90-day study, in which rats received diisopropyl methylphosphonate in the diet at doses of 0, 30, 100, or 300 mg/kg/day. The deaths were neither dose nor duration related and were not considered of toxicologic importance (Hart 1976). 

Even though all OP insecticides have a common mechanism of action, differences occur among individual compounds. OP insecticides can be grouped into direct and indirect ACHE inhibitors. Direct inhibitors are effective without any metabolic modification, while indirect inhibitors require biotransformation to be effective. Moreover, some OP pesticides inhibit ACHE more than PCHE, while others do the opposite. For example, malathion, diazinon, and dichlorvos are earlier inhibitors of PCHE than of ACHE. In these cases, PCHE is a more sensitive indicator of exposure, even though it is not correlated with symptoms or signs of toxicity. 

---