Toxicity Studies Of P-arsanilic Acid Nanoparticles On SD Rats

Arsanilic acid (P-Arsanilic acid, P-ASA) is widely used as a livestock feed additive because of its resistance to coccidiosis and antibacterial. But in recent years, because of animal residues and contaminated with feces and urine excretion in environmental issues become increasingly prominent.According to the small size, good antibacterial and growth-promoting effects and being fully absorbed of nano materials,our research group grind Arsanilic acid to nanoscale arsanilic acid (P-Asanilic acid nanoparticles, P-ASAP) Compared with the P-ASA, P-ASAP has good growth-promoting properties, and low residual amount of arsenic in the liver and feces,but its safety has not been reported. No safe, No market. So toxicological studies of P-ASAP was conducted by our group.Treatment 1. An acute toxicity treament:pre-test period was 7days, and experimental period was 14 days.36 SD rats (half male and female) were randomly divided into six groups:on the first day in the test, group Ⅰ, Ⅱ, Ⅲ, Ⅳ, Ⅴ were oral administered P-ASAP with the dose of 400mg,588mg,864.36mg,1270.6mg and 1867.8mg per kg, respectively.The ratio of two adjacent groups was 1.47, and the control group was administered with the same dose of normal saline, and observed for 14 days. Analyzed the median lethal dose (LD50) according to the statistical information about the morbidity and mortality.Treatment 2. Subacute toxicity treament:112 SD rats (half male and female) were randomly divided into 7 groups:each group was fed with basic diet plus P-ASA and P-ASAP, with the dose of 1/5,1/50 and 1/100 of their LD50, the control group with basic diet. Pre-feeding for 7 d, the experimental test for 36 d, conventional breeds them. Weighing weekly, clinical symptoms were observed and dissect the dead rats, mortality and morbidity were analyzed. On trial 18 d and 36 d,6 rats in each group were randomly selected and dissected, taking organs histopathological examinations; collected the serum for examines:(1) liver function (2) renal function (3) the level of oxygen free radicals and antioxidant enzyme activity (4) the liver and feces detect arsenic levels in which different valence (AS5, AS3, MMA, DMA).The results of acute toxicity treament showed that:the LD50 of P-ASAP was 765.036 mg·kg-1,95 percent confidence interval was 561.5 mg·kg-1～1006.95 mg · kg-1.The results of subacute toxicity treament showed that:1. Weight, morbidity and mortalityOn day 18 and 36, the weights of the groups with P-ASAP and P-ASA of the low-dose and mid-dose were significantly higher than the controls (P<0.01), the weights of P-ASAP groups higher than those of corresponding P-ASA groups. With reducing the dose, the morbidity of each group decreased. The morbidity of each group was higher than that of the corresponding P-ASAP group. The morbidity of P1 was much higher than N1.2. Pathological and histopathological changesP-ASAP and P-ASA major damage to the stomach, intestines, liver, kidneys, all of which are bleeding. High dose group of Arsanilic acid was more harmful to the liver and kidneys, and the P-ASAP harmful to the liver and lungs. In high dose group of P-ASAP,3 rat lung meat degeneration, hemorrhage, congestive induration, yellow lesions within the incision induration.3.Liver functionOn 18d and 36d, the ALT levels were higher than P-ASAP except the P-ASA group (P> 0.05). The levels of T-BIL, ALP and AST in P-ASA group were all lower than the P-ASAP group, and the difference of ALT was significant (P<0.05).4.Kidney function:On 18d and 36d, the levels of BUN and Cr in P-ASA groups were higher than the control group, and the P1 had a significant difference (P<0.05). The levels of BUN and Cr in each group of P-ASA were higher than the corresponding P-ASAP group (P<0.05).5. The levels of oxygen free radicals and antioxidant enzyme activityOn 18d and 36d, the SOD activity in each group of P-ASAP and P-ASA increased with the exposure dose increasing compared with the control group, and P1 was significantly higher than P3(P<0.05).On 18d and 36d, the GSH-Px activities in each group of P-ASAP and P-ASA were significantly lower than the control group (P<0.01), except the middle dose group, the GSH-Px activity in each group of P-ASAP are higher than the corresponding P-ASA group. (P<0.05).On 18d and 36d, the MDA level in each group increased incrementally with the exposure dose decreasing, and was highly significantly different compared with the control group(P<0.01); the MDA levels in each group of P-ASA was higher than the corresponding P-ASAP group.6.Different levels of arsenic valence in fecesOn 18d and 36d, AS3 and AS5 contents incremented with increasing exposure dose, and were higher than the control group (P>0.05). The N1, P1 AS3 contents were significantly different (P<0.05). On day-18 and 36, the DMA and MMA contents in each group were higher than the control, and incremented with the exposure dose. The DMA content in P1 increased highly significantly (P<0.01).7. Different levels of arsenic valence in liverOn 18d, the levels of AS3 were all higher than the control groups, and increments with the increasing exposure dose. Except the AS5 content in the N2, N3 and P3 on 18d and 36d, the levels of AS3 and AS5, DMA and MMA contents in each experimental group were higher than the control group, among which the levels of AS3 contents in P1 and P2 increased highly significantly (P O.01) and significantly (P<0.05), respectively; and the levels of DMA contents in N1 and P1 increased highly significant (P<0.01) and significantly (P<0.05), respectively.The Conclusion is comparing P-ASAP and P-ASA, the liver toxicity of P-ASAP was higher than P-ASA, but the renal toxicity, hepatic toxicity, oxidative toxicity and the toxicity of arsenic valence were all lower than P-ASA.