**6. Conclusions and research gaps**

**a.** Vegetable rapidly take up harmful substance(s) during short growth cycle. The acute and

**b.** Vegetables, either leafy or root, are often consumed raw. Thermal effect in cooking may affect advantageous sublimation of some harmful compounds, but this is not guaranteed

**c.** They are stored for short-term and consumed fresh, bringing about timely delivery of

**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

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

**b.** As it is a generally accepted fact that all drugs, including antibiotics have their side effect. It is only advantageous if taken to remove a more serious infection. Continuous exposure of farmers to residual antibiotics in dust [127] from soil fertilized with organic fertilizer exposes them to risk associated with accumulative effect of the gradual exposure.

**5. Guidelines for reuse of human and animal waste products as organic**

The WHO operational monitoring guidelines for the reuse of wastewater, excreta and greywater to fertilize crop strictly advocate certain validation requirements, operation monitoring parameter and technical measures, and verification monitoring are as stated in **Table 7** for safe reuse of waste. WHO guidelines [48] exemplify the die-off efficiency with a temperature of 50°C for at least 1 week before compost or ecohumus is considered safe for

long-term cytotoxicity effects on the consumers are unclear.

358 Organic Fertilizers - From Basic Concepts to Applied Outcomes

residual bioaccumulated antibiotics and other pollutants.

extracted antibiotics in the organic fertilizers.

**c.** Ecotoxic effects on other biotic components of the environment.

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

and

animals.

**fertilizers**

The WHO guidelines Vol 2 (Wastewater Use in Agriculture) and Vol 4 (Excreta and Greywater Use in Agriculture) [48, 153] form an evidence base and referral point for risk management strategies and risk mitigation. As such they are applicable for the planning and implementation of health aspects, especially related to pathogens, of use schemes for organic fertilizers, whether defined as biosolids, faecal sludge, manure, urine or different mixtures of these and with plant materials. The guidelines are building on microbial risk assessment (MRA) with identification and characterization of hazards, exposure assessment and risk characterization and management that can be applied with different levels of sophistication. This can be part of a scenario or model approach or built into a management approach. With modifications but with its different components it formed the base for "Human Health Risk Assessments of Pathogens in Land-applied Biosolids" [154] in the USA, with a model and scenario-based approach. It further forms a base for the simplified risk management approaches within the WHO sanitation safety plans (SSPs) [155].

For organic fertilizers in agriculture, the major differences in the hazard identification and characterization are locally specific, partly driven by the sources of the organic fertilizers used and partly reflecting the regional and socio-economic situations. In this context, the risk may partly be regarded higher in transient and developing global economies. It further relates to the treatment and application barriers, where regulations and enforcement against most often will be more stringent in developed regions and economies [156–158].

The WHO guidelines are further framed around a risk-reduction strategy accounting for a multiple risk barrier approach, which embrace both technical and handling barriers. This is applied to ensure a reduced exposure risk, which in relation to the application of biosolid, faecal sludge or manure etc. should reduce the risks in relation to both the crop and soil, to agricultural workers, communities or due to secondary run-off and impact. The technical reduction barriers here naturally play a fundamental role where different treatment methods have different efficiency. In the USA, a pathogen equivalency committee [159] should be able to assess new methods to ensure a high level of safety. Safety is also ensured in the way that the application is made in the agricultural fields, the crop selection and the impact of environmental factors (e.g. sunlight, temperature etc) on pathogen die-off. Again, large differences occur locally, seasonally and between different economic regions and social strata.

Even if the different risks and the level of risk can be identified, the epidemiological evidences are still poor for different types of organic fertilizers and especially if we should value this transmission route in relation to others. This further relates to different global regions and socio-economic conditions. The study outcomes from specified investigations in the USA, in EU or in Australia, for example, cannot be directly transferred to the conditions and situations on other continents and vice versa.

Low-cost treatment and handling approaches applicable for developing regions need further attention, where seasonal variations also need to be further accounted for.

The evidence base related to microbial die-off under different field conditions need to be substantially broadened and performed studies so far systematized in relation to effect.

The relationship between animal waste, water and environmental quality and human health have been addressed from a zoonotic livestock perspective, including management practices, exposure interventions and risk analysis but need much further attention related to organic fertilizers [160].

Crop contamination is documented but the relative impact between pre-harvest contamination by organic fertilizers and irrigation water on the one hand and post-harvest handling and storage contamination on the other needs to be further addressed. The specific situation with the potential impact of internalization and uptake of pathogens as compared to deposition on outer surfaces need much more attention and documentation, before long-term handling and management practices can be issued and related to modes of application.

Also, the specific situation, partly addressed in this chapter with uptake of antibiotics (and other organic contaminants) as well as the impact of use of these in livestock and among humans and the further fate in agricultural fields need to be addressed. Linked to this is also the large problem complex with the occurrence, transmission and impact of antibiotic-resistant bacteria especially, but also including other antimicrobial drugs.

At the current stage, the authors believe and conclude that the benefits with human- and animal-based organic fertilizers in the field far outmaster the potential negative impacts. However, we also firmly believe that a broadened evidence base and application of this in a risk-management perspective and framework will further enhance the positive benefits and counteract negative impact.
