**2. The use of antibiotics in veterinary medicine, characteristics, and environmental contamination**

The use of ATBs in the veterinary sector has been for many years an effective method used in animal husbandry, as these chemical agents promote animal growth, besides prevention and therapy against microorganisms [1]. Virtually, livestock activities, such as cattle, pigs, goats, and aquaculture, among others, make the use of these molecules to ensure animals' good quality and well-being, and in the case of activity for commerce, ensure product quality and market competitiveness.

Once ATBs are used and subsequently absorbed by animals, such compounds are metabolized. The metabolism degree depends on the type of substance and the treated species, as well as its age and health condition. If the compound is not metabolized, it will be eliminated in the feces and urine, reaching the environment (mainly soil and water) [3]. According to Kümmerer [1], 80% to 90% of ATBs are excreted as parent compounds in the environment, i.e., compounds that have not undergone metabolism in the animal body. According to Katz [4], the amount of eliminated ATBs varies according to the type of ATB, the dosage, and the type and age of the animal.

In the case of farm animals such as cattle, pigs, goats, and sheep, after reaching the soil through feces and urine, this group of drugs may be leached or suffer runoff to aquatic environments and still be in the soil [5]. Three other important soil and water introduction pathways to be mentioned are the packaging disposal in inappropriate places, especially on small farms, where the educational level of most farmers is low, the use of animal excreta for fertilization [6] and water direct contamination through aquaculture. The ATBs may also contaminate the environment by emissions during their fabrication process, although researchers consider this introduction pathway to be less relevant than those described above [7]. Thus, concern about the effects of these compounds in the environment has increased in recent years, which puts them as major environmental concern contaminants. Figure 1 exemplifies the main contami‐ nation pathways of veterinary ATBs in the environment.

ATBs differ by their chemical structure and mechanism of action, two characteristics that allow these compounds to be grouped into several classes, such as β-lactams, quinolones, tetracy‐ clines, macrolides, sulfonamides, and chloramphenicol, among others. Some of the main ATBs classes used in veterinary medicine, as well as some examples of compounds belonging to

> **Class Compounds** β-Lactams Amoxillin, piperacillin Tetracyclines Oxytetracycline, chlortetracycline Macrolides Erythromicin, tylosin Sulfonamides Sulfamethazine, sulfadiazine Amphenicol Florfenicol, chloramphenicol Fluoroquinolones Ciprofloxacin, enrofloxacin

ATBs may be of natural or synthetic origin. The first ATB, penicillin, which is produced by fungi of the Penicillium genus, that is, of natural origin, was discovered in 1929 by the physician and bacteriologist Alexander Fleming. Currently, the ATBs, that are small molecules with molecular weight of less than 1000 Da, are produced by chemical synthesis or by chemical

**2. The use of antibiotics in veterinary medicine, characteristics, and**

The use of ATBs in the veterinary sector has been for many years an effective method used in animal husbandry, as these chemical agents promote animal growth, besides prevention and therapy against microorganisms [1]. Virtually, livestock activities, such as cattle, pigs, goats, and aquaculture, among others, make the use of these molecules to ensure animals' good quality and well-being, and in the case of activity for commerce, ensure product quality and

Once ATBs are used and subsequently absorbed by animals, such compounds are metabolized. The metabolism degree depends on the type of substance and the treated species, as well as its age and health condition. If the compound is not metabolized, it will be eliminated in the feces and urine, reaching the environment (mainly soil and water) [3]. According to Kümmerer [1], 80% to 90% of ATBs are excreted as parent compounds in the environment, i.e., compounds that have not undergone metabolism in the animal body. According to Katz [4], the amount of eliminated ATBs varies according to the type of ATB, the dosage, and the type and age of

them, are shown in Table 1.

**Table 1.** Important classes and examples of veterinary ATBs.

108 Emerging Pollutants in the Environment - Current and Further Implications

modification of naturally occurring compounds [1].

**environmental contamination**

market competitiveness.

the animal.

**Figure 1.** Introduction pathways of veterinary antibiotics in the environment. Adapted from Boxall et al. [7].

Of all animal husbandry activities, fish farming may be the one that contributes with the largest share of direct contamination of ATBs in the environment. In general, these compounds are administered in fish farming through three forms: inclusion in food (the most practiced and used in tank-nets crops), baths (restricted to water-soluble compounds and administered in tanks with interrupted water renovation during treatment), and finally through hypodermic injection (high cost). According to Shao [8], ATB inclusion in the feed is the most convenient way due to lower amounts of drug required in comparison with administration through water, for example. Consequently, the number of such molecules that enter the aquatic environment would be lower, according to this author.

Cravedi [9] reported that about 7% to 9% of the ingested oxytetracycline was absorbed during the passage through the gastrointestinal tract of rainbow trout, and thus 93% to 99% polluted the environment. Rogstad et al. [10] observed absorption of less than 1% after 24 h of oxyte‐ tracycline administration and of 2.6% after 72 h. Among sick fish, low intake rate is common due to reduced palatability of the diet. Thinking of decreasing the contamination of aquatic environments, hypodermic injection or vaccine has been used in many fish farms.

Even with the use of ATBs in aquaculture facilities, limited data on types and amount used of these products are not available. In the study of Sapkota et al. [11], a list of 26 antibiotics used in the 15 countries that more practiced aquaculture by the year of 2005 according to FAO was presented, which comprises representatives of the class of sulfonamides, tetracyclines, penicillins, quinolones, nitrofurans, macrolides, aminoglycosides, and chloramphenicols.

In general, ATBs used in aquaculture are oxytetracycline, florfenicol sarafloxacin, erythromy‐ cin and sulfonamides potentiated with trimethoprim or ormetoprim [12]. In Brazilian fish farms, only florfenicol-based ATBs are approved by the Ministry of Livestock Supply (MAPA) for use in tilapia [13], although others, such as oxytetracycline, are also used. Both are repre‐ sentatives of the classes of chloramphenicols and tetracycline, respectively, and the main form of use of these drugs has been through inclusion in the feed. Florfenicol is a fluorinated analog of thiamphenicol [14], which binds to 50S and 70S ribosome subunits [15], inhibiting protein synthesis transpeptidation of Gram-negative and Gram-positive bacteria [16]. Oxytetracycline is an antibacterial agent, which is effective in the treatment of infections caused by Grampositive and Gram-negative bacteria, mycoplasmas, and large viruses. It inhibits protein synthesis by preventing the association of aminoacyl-tRNA to the bacterial ribosome [3].

As with most chemical agents, the destination and behavior of ATBs in the environment is influenced by the physical and chemical characteristics of the compounds (molecular structure, size, shape, solubility, hydrophobicity) and of the soil (pH, texture field organic), besides the climatic conditions (temperature, precipitation) [17] and biological factors (microbial degra‐ dation). ATBs that have high potential of sorption (*K*d) to the soil particles, for example, tend to accumulate and persist in this matrix, unlike those who have low *K*<sup>d</sup> value, which are easily transported to aquatic environments [18]. According to Regitano and Leal [19], in general, compounds with *K*d <5 L kg-1 values and half-life of less than 21 days, such as sulfonamides (*K*d = 0.2 to 2.0 L kg-1), for example, have relative persistence and can be leached into ground‐ water, unlike those that have *K*d > 5 L kg-1 and half-life of more than 21 days, which tend to accumulate in the soil surface layers, as is the case of compounds belonging to the group of tetracyclines and fluoroquinolones (*K*<sup>d</sup> = 70 at 5.000 L kg-1). *K*<sup>d</sup> values may vary considerably for certain compounds in different types of soil [20].

According to Tolls [21], ATBs sorption may also be influenced by cation exchange processes, by adsorption to the surfaces of clay minerals, by complexing reactions with metal ions and by hydrogen bridges. For example, in the study of Sassman and Lee [22], the main mechanism involved in the sorption of tetracyclines was cation exchange, and sorption potential was influenced by the environment pH and by the cation exchange capacity of clay minerals prevailing in the soil matrix.

ATBs, which are mostly complex molecules, may have different functionalities within the same molecule, which causes that under different pH conditions they can be neutral, cationic, anionic, or zwitterionic. Due to different functions within a single molecule, its physicochem‐ ical and biological characteristics, such as the log Kow [23], sorption behavior, photo reactivity, antibiotic activity, and toxicity, can change with pH. Other factors that are pH dependent are solubility, hydrophobicity, and log Kow. Regarding drugs solubility being pH dependent, this can affect not only destination and transport, but also the assessment of environmental effects, which includes toxicological assessments [24], which are going to be portrayed in this chapter.


a Values obtained from the United States National Library of Medicine: http://toxnet.nlm.nih.gov/.

b Not available

way due to lower amounts of drug required in comparison with administration through water, for example. Consequently, the number of such molecules that enter the aquatic environment

Cravedi [9] reported that about 7% to 9% of the ingested oxytetracycline was absorbed during the passage through the gastrointestinal tract of rainbow trout, and thus 93% to 99% polluted the environment. Rogstad et al. [10] observed absorption of less than 1% after 24 h of oxyte‐ tracycline administration and of 2.6% after 72 h. Among sick fish, low intake rate is common due to reduced palatability of the diet. Thinking of decreasing the contamination of aquatic

Even with the use of ATBs in aquaculture facilities, limited data on types and amount used of these products are not available. In the study of Sapkota et al. [11], a list of 26 antibiotics used in the 15 countries that more practiced aquaculture by the year of 2005 according to FAO was presented, which comprises representatives of the class of sulfonamides, tetracyclines, penicillins, quinolones, nitrofurans, macrolides, aminoglycosides, and chloramphenicols.

In general, ATBs used in aquaculture are oxytetracycline, florfenicol sarafloxacin, erythromy‐ cin and sulfonamides potentiated with trimethoprim or ormetoprim [12]. In Brazilian fish farms, only florfenicol-based ATBs are approved by the Ministry of Livestock Supply (MAPA) for use in tilapia [13], although others, such as oxytetracycline, are also used. Both are repre‐ sentatives of the classes of chloramphenicols and tetracycline, respectively, and the main form of use of these drugs has been through inclusion in the feed. Florfenicol is a fluorinated analog of thiamphenicol [14], which binds to 50S and 70S ribosome subunits [15], inhibiting protein synthesis transpeptidation of Gram-negative and Gram-positive bacteria [16]. Oxytetracycline is an antibacterial agent, which is effective in the treatment of infections caused by Grampositive and Gram-negative bacteria, mycoplasmas, and large viruses. It inhibits protein synthesis by preventing the association of aminoacyl-tRNA to the bacterial ribosome [3].

As with most chemical agents, the destination and behavior of ATBs in the environment is influenced by the physical and chemical characteristics of the compounds (molecular structure, size, shape, solubility, hydrophobicity) and of the soil (pH, texture field organic), besides the climatic conditions (temperature, precipitation) [17] and biological factors (microbial degra‐ dation). ATBs that have high potential of sorption (*K*d) to the soil particles, for example, tend to accumulate and persist in this matrix, unlike those who have low *K*<sup>d</sup> value, which are easily transported to aquatic environments [18]. According to Regitano and Leal [19], in general, compounds with *K*d <5 L kg-1 values and half-life of less than 21 days, such as sulfonamides (*K*d = 0.2 to 2.0 L kg-1), for example, have relative persistence and can be leached into ground‐ water, unlike those that have *K*d > 5 L kg-1 and half-life of more than 21 days, which tend to accumulate in the soil surface layers, as is the case of compounds belonging to the group of tetracyclines and fluoroquinolones (*K*<sup>d</sup> = 70 at 5.000 L kg-1). *K*<sup>d</sup> values may vary considerably

According to Tolls [21], ATBs sorption may also be influenced by cation exchange processes, by adsorption to the surfaces of clay minerals, by complexing reactions with metal ions and by hydrogen bridges. For example, in the study of Sassman and Lee [22], the main mechanism involved in the sorption of tetracyclines was cation exchange, and sorption potential was

for certain compounds in different types of soil [20].

environments, hypodermic injection or vaccine has been used in many fish farms.

would be lower, according to this author.

110 Emerging Pollutants in the Environment - Current and Further Implications

c Values from Białk-Bielinska [26].

**Table 2.** Physical and chemical characteristics of some veterinary ATBs.

Generally, pharmaceutical products are compounds characterized by a complex chemical structure that have very variable molar masses (172 at 916 g mol-1), low volatilization potential, several ionizable functional groups (amphoteric molecules), different p*K*a values, and low octanol–water partition coefficient values (log Kow), which indicates low bioaccumulation potential [25]. The log Kow indicates the tendency of an organic chemical product to partition into lipids or fats and adsorb to particles of soils, sediments, biomasses, and muds [23]. Table 2 shows some of these characteristics described above for some ATBs.
