Relationship Between Acute Toxicity Of Organic Pollutants To Rats And Mice In Different Exposure Routes

With the rapid development of modern industry, a large number of new synthetic compounds are released into the environment and pollute the ecosystems. Organic pollutants carried by industrial wastewater, as well as sewage and waste gas, enter into the soil and water environments. They can be accumulated in animals via bioaccumulation, break the DNA strand and have toxic effects through the reactions with certain groups of the DNA bases. Acute toxic effects of chemicals to mammals are important indicators in the ecological risk assessment. Investigation on the acute toxic effect to the organic pollutants is not only useful in the evaluation of the hazardous and potential toxic effects of organic pollutants on mammals, but also helpful for understanding the toxic mechanisms.In this thesis, the relationship between the acute toxicities of organic pollutants to mice and rats from different exposure routes were investigated basing on the determination and collection of toxicity data. The regression equations between toxicity values and molecular fragments of compounds were established. The toxicity differences of organic pollutants to mice between intragastric and injections routes were discussed. The influence of pKa of compounds to rats in different routes were revealed. Basing on comparison between the similarity and difference of toxicities to mice and rats, the effect of exposure routes to interspecies correlation were discussed. The acute toxicities of aromatic compounds to mice in intragastric and intraperitoneal routes were determined. The main conclusions are as follows:(1) Analysis on the relationships between the acute toxicities to mice in intragastric, intravenous, subcutaneous and intraperitoneal injection routes shows that toxicity sensitivity of intravenous administration is the highest and the intragastric administration is the lowest. The toxicities in intravenous were well related to that in subcutaneous and intraperitoneal routes, but the differences of bioavailability and kinetics can cause the differences in toxicities in three injection routes.(2) Investigations on the acute toxicity of 527 compounds to rats in intragastric, intravenous, intramuscular and intraperitoneal injection routes reveal that the log1/LD50 values in intravenous were slightly higher than that in intraperitoneal route, but significantly higher than that in intragastric administration. The differences of toxicities in four exposure routes were investigated based on the stepwise regression equations, the results indicate that descriptors of Kow and percentage of positive ions could improve the correlation coefficient between the toxicities in intravenous and intraperitoneal/intragastric routes. The hydrophobicity and acidity or basicity of compounds could affect the absorption in mice or rats, resulting in different toxicities from different exposure routes. Besides, the acute intragastric toxicity tests were more complex than acute injection tests, which could induce the interspecies correlation in intragastric administration.(3) No well correlation in log1/LD50 between homologues was observed. The toxic contributions of fragments were obtained from multiple linear regression equations. The toxic contributions in intragastric and injection routes were similar for most fragments. However, slightly differences were found for a few fragments. Analysis in the relationship of toxicities between intragastric and injection routes shows that the correlation was a little poor with a low correlation coefficient of 0.75. Most compounds have similar toxic contributions because chemicals have same toxic mechanisms to the same organism in different exposure routes. Some compounds are hydrolyzed in gastrointestinal tract, resulting in the differences in the toxic contribution between intragastric and injection routes.(4) Acute toxicity tests of aromatic pollutants to mice in intragastric and intraperitoneal routes show that the toxicities in intraperitoneal were higher than that in intragastric routes for most compounds. The absorption rates of compounds decrease in the gastrointestinal tract along with the increase of acidity in exposure environment, leading to the reduced the toxicity in the intragastric administration. The dissociation of phenolic compounds varies with the pH in the exposure environment. The decrease of molecular forms of phenolic compounds weaken the ability of penetrating cell membranes of the compounds, so that the toxicities of compounds to mice in intragastric administration are lower than that in intraperitoneal routes. No significantly progressive increase in toxicities of fluorobenzene, bromobenzene and iodobenzene was observed in intragastric and intraperitoneal routes. The reason is due to the difference in electronic effect. The induced effect is greater than the conjugative effect on fluorine atoms, but bromine and iodine atoms.