**4. Residual antibiotics (AB) and antibiotic-resistance genes (ARGs) in organic fertilizers**

Veterinary drugs are introduced into the environment through a number of routes like direct applications as in aquaculture, application of manure and/or slurry to agricultural fields and through disposal of wastes during the production processes. An investigation also indicate a link between the proximity of swine farms exposed to these antibiotics through contact with animal feed and development of antibiotic resistance in bacteria among small wild animal accessing into barns and feed storage areas [115]. The presence of drugs and their metabolites in the environment have frequently been reported. For instance, low levels (<1 μg/L) of antibiotic residues have been detected in surface water samples in both Germany and the USA collected from sites considered susceptible to contamination [116]. The residual antibiotics in organic fertilizers using animal manure from large-scale livestock farms (mainly including slurry and dung from pigs, cows and chicken) have been investigated with their presence confirmed [117].

The residual antibiotics found in organic fertilizers may emanate from administration to humans either as prophylaxis or for therapeutic purposes. They are also being used as components of animal feeds to promote growth, to treat or prevent diseases of farm animals and sometimes against diseases in plants [118–126]. Hence, tetracycline concentration, for example, in liquid organic fertilizer could be as high as 20 mg kg−1 [127]. So, the use of manures as organic fertilizers on farmland containing antibiotics is fast becoming a serious environ‐ mental issue of concern [128]. Up to 200,000 tons of antibiotics are both used per annum by humans and administered to farm animals [129]. About 70% are consumed as growth pro‐ moters [131, 131], irrespective of the 1998 EU embargo [132, 133]. Massive utilization of antibiotics in veterinary practices remains in China, Russia, Europe and the USA [134, 135] where the largest producer and user of antibiotic is China. Tens of thousands tons of penicillin and tetracycline derivatives were produced in early 2000s [136]. The prescription in China is/ was equally over double the amount in the Americas [137].

Therefore, antibiotics that end up in manure or fertilizers might have come from any of the following:


been performed related to contamination of crops used for medicinal products and supple‐ ments [105]. The direct exposure of agricultural workers is also significant and relates to different transmission routes, as well as the frequency and duration of exposure. Farmworker exposure has been examined [106, 107], including the impact on family members [108]. Direct exposure relates to the level of manual work and mechanization. The risk further relates to the type of fertilizer, from human and animal urine to untreated or treated wastewater, manure or human excreta. A special situation is when stored organic fractions or mixture thereof function as breeding site for fly/mosquito vectors of parasitic disease or attract vermin's that can act as carriers of pathogens. This is for example considered in the USEPA guidelines [109]. In addition to microbiological contaminants, organic fertilizers may, especially when sludge constitute parts of the input material, contain metals and other chemicals that may affect the receiving soils as well as be of relevance for occupational exposures. To appropriately assess human risk from chemicals found in biosolids, the form of the chemicals, and their fate, transport and bioavailability needs to be known, for example, arsenic, lead, mercury, antibi‐

356 Organic Fertilizers - From Basic Concepts to Applied Outcomes

Jerkins et al. [110] reported two studies that were suggestive that compost workers were affected by fungi. One cross-sectional study in Germany reported a significant increase in symptoms from lungs and airways as well as dermal effects and related these to increased exposure to fungi and Actinomycetes. The other was a prospective study in multiple US cities where significant increases in eye and skin irritation occurred and fungal colonization was documented but no serological evidence of other infections was reported. Indirect evidences were presented by Harrison and Oakes [111] that reported 39 incidence of illness among neighbours to biosolids application sites. The evidences were however not appropriately

The infection risks have been estimated using quantitative microbial risk assessment (QMRA) when urine or human faeces are used for garden fertilization [112]. A study in South Africa reported enhanced infection risks of *Salmonella* sp. and *Ascaris* sp. associated with spinach or carrots fertilized with human excreta [113]. An assessment of the health risk associated with daily consumption of vegetables (lettuce, 11.5 g) fertilized with compost was done by Wata‐ nabe et al. [114]. If the concentration of pathogenic virus in compost, for example is 10−1–102 PFU/g of lettuce, the risk would still be higher than the WHO tolerable annual infection risks.

**4. Residual antibiotics (AB) and antibiotic-resistance genes (ARGs) in**

Veterinary drugs are introduced into the environment through a number of routes like direct applications as in aquaculture, application of manure and/or slurry to agricultural fields and through disposal of wastes during the production processes. An investigation also indicate a link between the proximity of swine farms exposed to these antibiotics through contact with animal feed and development of antibiotic resistance in bacteria among small wild animal accessing into barns and feed storage areas [115]. The presence of drugs and their metabolites

otics.

backed up.

**organic fertilizers**

**c.** Effluents from pharmaceutical industries [138, 139]

Pharmaceuticals are excreted to the environment through the excreta (either mainly through the urine or through the faeces) from humans or animals in a semi-digested active form or as derivatives and end up in wastewater or biosolid. Some of them may be retained in the final organic fertilizers (biosolids), as well as in wastewater and reach surface water and sediments [127, 140, 141]. All kinds of manures, wastewater sludge and excreta from human are vehicles for carrying residual antibiotics in the environment [142–146]. Zhang et al. [146, 147] reported that residual antibiotics were highest in pig manure, followed by chicken manure and cow manure in that order, but this is mainly a reflection of the local situation. The concentration is, as expected, higher from large-scale agriculture farm than from subsistence farm. Rainfall will naturally add to the run-off of these from agricultural land to surface and groundwater. It also enhances the potential for distribution to other biomes with ecotoxic effects. They also get lodged in the soil organisms like earthworms, soil arthropods, fungi and bacteria.

Like internalized pathogens, the potential high uptake of antibiotics by vegetables fertilized with biosolids globally is of enhanced public health concern [148, 149].

Future attention is needed in the issue of bioaccumulation in vegetable with residual antibiotic because


Therefore, they bring about any of the following environmental impacts:

**a.** Emergence of bacterial resistance through long-time exposure to sublethal concentration of the residual antibiotics, genetic variation resulting from innate adaptative drives of the bacteria and also provide a pseudo-biofilm environment for exchange of antibioticresistant genes (ARGs) [150–152]. It is an established fact that exposure to low-level or sublethal or sub-minimum inhibitory concentration (sub-MIC) of antibiotic drug has effects on the bacterial physiology and its genetic or phenotypic variability, and the potentials of antibiotics to function as signalling molecules. All these factors contribute to prompt emergence and spread of antibiotic-resistant bacteria among humans and animals.

Laboratory-based methods have been developed to determine the effect of exposing bacteria to sublethal concentrations (sub-MIC) of antibiotics. This has affirmed the implication of the antibiotics in environment, including those in organic fertilizers, on the emergence of antibiotic resistance. These kinds of research also encompass the *in vitro* pharmaco dynamic models, concentration and exposure time of susceptible bacteria to selected conventional antibiotics before the emergence of resistance. The concentration variations to be employed for such studies will be informed by the concentration of the extracted antibiotics in the organic fertilizers.

