Two-stage Model Predict The Time-dependent Toxicity Of Antibiotics And Mixtures To Chlorella Pyrenoidosa

Antibiotics is a kind of semi-synthetic or synthetic compounds with natural resistant microbial activity produced by the micro-organisms(including bacteria, fungi, actinomycetes genus) or higher plants and animals in the process of life. According to the chemical structure, antibiotics can be divided into aminoglycosides, ?- lactams, tetracyclines, quinolones, macrolides, polypeptides, amide alcohols, lincosamides and etc. Antibiotics are primarily used for the prevention and treatment of human and animal diseases, and later also as a growth promoter in feed to promote animal growth and development. However, due to mass production and serious abuse, some antibiotics which can not be absorbed by the human and animal body probably enter into the environment and do harm to the ecological balance and biological hazards. The contaminants in the actual environment generally are of low dose and mixture characteristics. Meanwhile, different pollutants have different toxicity profiles at different exposure times. Thus, the assessment on the time-dependent toxicicity of antibiotics together with mixtures has important practical Significance.Therefore, as for the phenomenon that different antibiotic and mixtures may have different toxic variations at different exposure times, the chlorella pyrenoidosa was selected as test organism, the toxicity of 20 kinds of antibiotics and their mixtures was determined by the time-dependent microplate toxicity analysis at the time of 0,12,24,48,72 and 96 h. Based on the toxicity data of single antibiotic, uniform design ray method was used to design pentanary mixture with the same kind of anbtibiotics(28 rays) and twenty-antibiotic mixtures(15 rays). The toxicity of these mixture rays were determined at six different exposure times. The two-stage model was used to evelate the toxicity of these mixture rays. The main contents and results of this paper are summarized as follows:(1) Twenty kinds of antibiotics in the 48 ~ 96 h has a good concentration- response relationship, different kinds of antibiotics have different time-dependent toxicity characteristics: the toxicity changing of most antibiotics with time, such as significant increase of tobramycin after 4 h, but no toxicity at the first four time points, increase first, decrease after of piperacillin sodium, ampicillin sodium enrofloxacin, decrease first, increase after of chlortetracycline hydrochloride, doxycycline hyclate, metacycline and tetracycline hydrochloride, and almost no toxicity of norfloxacin.(2) Four groups of pentanary mixture with the same kind of antibiotics containing 28 rays 3 mixture mixture systems with different antibiotics containing 15 rays were determined by unifrom design ray method. Each mixture ray had a good the concentration-response relationship at each time point, and the toxicity of the mixture was of time-dependency: the toxicity of some mixtures gradualy increased with time, some gradualy changed from hormesis to the toxicity. The toxicity of pentanary mixture systems with the same antibiotics correlated well with concentration ratio of some certain component.(3) Acorrding to the concentration additive model, most of pentanary mixtures diplaying additive effect except those mixture rays exhibiting hormesis. According to the IA, most of mixtures exhbited additive action, and few mixtures showed obvious synergism or antagism with time-dependency. In all, two-stage model can well evelate the time-dependent toxixity of most of mixtures excetp those mixtures displaying hormesis, synegism or antagonism.