## 4 Limitations of Using Plant Products as Bioherbicides
### Effect of Nepetalactone and Phloretin on Non-Target Organisms
#### 4.3.3 Effects on Crops  
Bioherbicides possess the potential for phytotoxic effects on crops, necessitating precise and judicious application to ensure crop safety and effective weed management. While data on the effects of phloretin on crops are not yet available and studies are still in the experimental phase, some insights into the impact of nepetalactone have already been documented. [PERSON] et al. [38] conducted in vitro tests to evaluate the effects of _N. tranjensis_ EO on the germination of weed and crop seeds. Among the weed species, _Rumex crispus_ seeds showed a high level of resistance to the _N. tranjensis_ EO, while the lowest concentrations of the EO completely inhibited the germination of _Stellaria media_ seeds. Regarding crops, concentrations as low as 0.3% of the EO significantly reduced the germination of _Lepidium sativum_ seeds, while concentrations of 0.5% completely inhibited the germination of _Lactuca sativa_ seeds. However, the _N. tranjensis_ EO, even at the highest concentration, had no effect on the germination of _Brassica napus_ seeds. When using specialized metabolites as bioherbicides, careful selection of species and doses is crucial for effective weed control while minimizing crop damage. Laboratory studies offer initial guidance, but field conditions, including environmental variability and biotic interactions, can impact efficacy. Further field research is needed to determine optimal doses and application methods that ensure crop safety and sustainable weed management. Regulatory and Economic Challenges Associated with the Application of Nepetalactone and Phloretin in Commercial Agriculture  
The application of bioherbicides in commercial agriculture offers promising alternatives to synthetic chemicals, but their production and economic feasibility require the careful consideration of various factors. The chemical synthesis of compounds such as NL can be challenging and expensive, especially due to the presence of different stereoisomers of NL. Producing a specific isomer requires precisely controlled reaction conditions, which can increase synthesis costs. Furthermore, the process may involve multi-step reactions, each carrying additional costs, including the use of specialized reagents, catalysts, and equipment [83; 320]. On the other hand, using a natural source, such as the distillation of NL from plants, may be a more economical option. Extraction from plants typically involves simpler processes, such as distillation or solvent extraction, which are less demanding in terms of equipment and reagents. This approach also has the advantage of lower costs compared to chemical synthesis. However, production from natural sources may be limited by the availability of raw materials and seasonal variations in plant yields, which can increase costs [321]. The use of phloretin for bioherbicidal formulations largely involves its isolation from natural sources, primarily domesticated apples. Phloretin could be obtained from apple trees residues (leaves, bark, and roots) through the deglycosylation of phlorezin, which is present in enormously large quantities in apple tissues (from 4 to 18% of leaf tissue DW, depending on the cultivar and the season) [216]. In view of the relatively expensive and time-consuming extraction of phloretin, the need arose to find more economical solutionsfor the rapid production of large quantities of phloretin. Recently, [PERSON] et al. [322] constructed an artificial biosynthetic pathway for phloretin through a modular engineering strategy. They enabled the production of phloretic acid, phloretin, and phloretin in _Escherichia coli_. Producing phloretin or its derivatives in microbial cell factories could provide a fast and cost-effective approach for their use in sustainable weed management practices. Comparing the effect of NL with other known phenolic compounds such as ferulic acid or juglone, the following can be observed.