A sound assessment of in silico models and their applicability domain can support the use of new approach methodologies (NAMs) in chemical risk assessment and requires increasing the users’ confidence in this approach. Several approaches have been proposed to evaluate the applicability domain of such models, but their prediction power still needs a thorough assessment. In this context, the VEGA tool capable of assessing the applicability domain of in silico models is examined for a range of toxicological endpoints. The VEGA tool evaluates chemical structures and other features related to the predicted endpoints and is efficient in measuring applicability domain, enabling the user to identify less accurate predictions. This is demonstrated with many models addressing different endpoints, towards toxicity of relevance to human health, ecotoxicological endpoints, environmental fate, physicochemical and toxicokinetic properties, for both regression models and classifiers.

The Numidian cypress (Cupressus sempervirens var. numidica, C. numidica hereafter) is a rare, almost unknown, endemic taxon of Tunisia whose conservation has long been hampered by human activities, taxonomic uncertainty and limited ecological knowledge, with only 64.33 ha of its populations remaining. Although recent genetic studies have confirmed its native status and long-term isolation, detailed information on its distribution, population structure and threats remain lacking. This study provides the first comprehensive assessment of C. numidica across its remaining range. Field surveys revealed that the species persists in only three small, fragmented forests, Bou Abdallah, Sidi Amer, and Dir Satour, covering a total of 64.33 ha. Soil analysis revealed some differences among sites, with Bou Abdallah showing higher clay content and Dir Satou exhibiting the highest levels of nitrogen, organic carbon, Olsen P, and available Mn and Mo. Climatic analyses indicate a semi-arid Mediterranean environment with pronounced summer droughts and a clear warming trend. Trees showed widespread damages, due to intensive grazing, tree cutting, crown dieback (drought), and pest and pathogen attacks. Natural regeneration was limited, and the condition of affected trees ranged from moderate to severe, with Bou Abdallah showing the highest levels of degradation. Notably, the severe fungal pathogen Seiridium cardinale, causal agent of cypress canker, was detected on C. numidica for the first time, highlighting an urgent conservation concern. Our results point to a staged conservation approach over time. In the immediate term (within 1 year), urgent monitoring and management of S. cardinale is needed. In the short term, efforts should focus on protecting carefully selected areas, about 5–10 regeneration microsites per forest, from grazing to support natural regeneration, reduce ongoing soil degradation, and establish clonal and seed-production plantations along with long-term seed storage. In the long term, the survival of C. numidica will only be possible with the active involvement of local communities, through awareness campaigns, adapting traditional practices such as gdel, and developing small-scale ecotourism that provides sustainable livelihoods while reinforcing support for conservation.