Stage-Dependent Embryolethality of Diclofenac Sodium: Quantitative Assessment of Dose–Time Interaction and Critical Windows of Susceptibility in the In Ovo Chicken Embryo Model

(1) Background: Diclofenac sodium is a drug with reported developmental toxicity in several non-mammalian and mammalian models. This study aims to evaluate the stage-dependent embryolethality of diclofenac sodium according to developmental stage using the chicken (Gallus gallus domesticus) embryo in ovo model, a system widely used in veterinary and avian developmental toxicology screening. The study focuses specifically on quantitatively determining the “critical sensitivity windows” between the early (day 7) and late (day 14) embryonic stages. (2) Methods: Fertilized chicken eggs (Gallus gallus domesticus) were exposed to different doses (3.125–50 mg/kg) of diclofenac sodium, and mortality rates were analyzed. (3) Results: The data indicated that diclofenac toxicity is highly dependent on the developmental stage (p = 0.002). While the LD50 value for the early stage (day 7) was calculated as 20.67 mg/kg, (95% CI 6.79–860.87 mg/kg; wide interval reflecting low precision and steep response), embryos at the late stage (day 14) were found to be more resistant, with an LD50 value of 32.16 mg/kg (95% CI 27.77–37.90 mg/kg). The calculated Potency Ratio of 1.55 indicates that 7-day-old embryos are more sensitive to diclofenac. (4) Conclusions: This study provides model-specific preliminary quantitative data on the stage-dependent embryo mortality profile of diclofenac sodium in chicken embryos. The higher mortality observed on day 7 is consistent with a window of susceptibility during early organogenesis that may be associated with immature detoxification pathways (e.g., hepatic CYP450) and active organic anion transport (e.g., Oatp1d1) reported in other developmental models. However, these mechanisms were not directly measured here. These findings contribute to comparative developmental toxicology and the One Health-focused assessment of NSAID exposure in animal species, emphasizing the importance of considering “timing of exposure” in developmental toxicity assessments. Furthermore, no extrapolation to mammalian pregnancy or human clinical guidelines is implied.