Experimental study on subacute toxicity of guanidine azotetrazolium in adult SD rats
Objective To explore the subacute oral toxicity of guanidine azotetrazolium(GZT)in rats,and to provide basis for the safety evaluation of occupational contact population.Methods A total of 60 healthy adult SD rats free of specific pathogens were randomly divided into control group,low dose group,medium dose group,high dose group dose and satellite group,with 10 rats in each group.Rats in the low,medium and high dose groups were given 125 mg/kg·bw,250 mg/kg·bw and 500 mg/kg·bw GZT-carboxymethyl cellulose suspension by oral gavage,respectively,while the control group was given an equal volume carboxymethyl cellulose solution by gavage once a day for 28 consecutive days.Animals in the satellite group were observed for 14 days after having been exposed for 28 days.The changes of toxic symptoms,body weight,food utilization,blood routine,serum biochemical indicators,organ coefficients and histopathology of the rats were observed.SPSS 23.0 was used for statistical analysis,and the test level was α=0.05.Results During the experiment,animals were in good health.There were no significant differences in the body weight of male and female rats between different dose groups and the control group(P>0.05),while the food utilization rate of the high dose group was lower than that of the same sex control group(P=0.010).Red blood cell counts,hemoglobin levels,hematocrit levels of female rats in high dose group were lower than those of the same sex control group(P=0.008,P=0.010,P=0.001,respectively).Blood urea nitrogen(BUN),creatinine(CREA)and uric acid(UA)levels of male rats in high dose group were higher than those in the same sex control group(P=0.024,P=0.009,P=0.001,respectively).The cholesterol levels in medium and high dose groups were higher than that in the same sex control group(P=0.030,P=0.001,respectively).The renal organ coefficients of rats in high dose group increased when compared with the same sex(P=0.001,P=0.002,respectively).The thymus organ coefficients of male rats in medium and high dose groups were lower than those in the same sex control group(P=0.027,P=0.001,respectively).The spleen organ coefficient of the high dose group was lower than that of the same sex control group(P=0.005).Conclusions High dose(500 mg/kg·bw)of GZT could affect the blood system of female rats and the kidney and immune function of male rats.The effects were reversible after discontinued the test substance.The no observed adverse effect level(NOAEL)for subacute oral toxicity of GZT was 125 mg/kg·bw under the conditions of this experiment.