目的　考察抗新型冠状病毒卵黄抗体喷雾剂经鼻腔和口咽部重复给药后动物的全身和局部毒性反应，以及皮肤的致敏性和眼刺激性，评价其非临床安全性。方法　ICR小鼠每天1次滴鼻腔和滴口咽部给予供试品（71.04、142.08 μg/d）2周，评价毒性反应。SD大鼠每天2次滴鼻和口咽喷雾给予供试品（639.35、1 278.70、2 557.40 μg/d）4周后，评价毒性反应、靶器官、毒代动力学以及停药4周后恢复情况。豚鼠背部皮肤涂抹给予0.4 mL浓度2 367.96 µg/mL供试品，致敏并激发，评价皮肤过敏反应情况。新西兰兔每天3次、连续7 d结膜囊内滴眼给予浓度2 367.96 µg/mL供试品，评价对眼的刺激性。结果　2个剂量组ICR小鼠2周后均未见明显全身毒性反应，未见不良反应剂量为142.08 μg/d；142.08 μg/d组给药局部可见刺激性反应，局部安全剂量（71.04 μg/d）为临床拟用最高总剂量的31.17倍。3个剂量组SD大鼠4周后血药浓度均低于定量下限（0.74 μg/mL），动物未见明显全身毒性反应，未见不良反应剂量（2 557.40 μg/d）为临床拟用最高总剂量的112.20倍，仅高剂量组雄性大鼠给药局部（鼻黏膜和固有膜）出现可恢复的刺激性反应。豚鼠主动皮肤过敏试验和新西兰兔眼刺激反应试验结果均为阴性。结论　供试品经鼻腔和口咽部给药显示出良好的安全性，剂量达到临床拟用最高剂量的100倍以上，未见全身毒性反应；大剂量经鼻和咽部多次给药，虽对SD大鼠局部有一定的刺激性，但停药后可恢复。临床制剂浓度下使用供试品，无皮肤过敏反应或眼刺激性。

Objective　To evaluate the non-clinical safety of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) chicken egg yolk immunoglobulin (IgY) spray by investigating the systemic and local toxicities, skin sensitization and potential eye irritation through repeated nasal and oropharyngeal administration in animals. Methods　Toxicity in ICR mice was evaluated after nasal and oropharynx drop administration of anti-SARS-CoV-2 IgY (71.04, 142.08 μg/d) once daily for 2 weeks. After SD rats were administrated with anti-SARS-CoV-2 IgY (639.35, 1 278.70, 2 557.40 μg/d) by nasal drop and oropharyngeal spray twice daily for 4 weeks, toxicity, target organs, toxicokinetics, and recovery after 4 weeks withdrawal were assessed. Active skin anaphylaxis test was used to evaluate the allergenicity after application of 0.4 mL anti-SARS-CoV-2 IgY (2 367.96 µg/mL) on backs of guinea pigs. New Zealand rabbits were given anti-SARS-CoV-2 IgY eye drops (2 367.96 µg/mL) 3 times daily for 7 d to evaluate the eye irritability. Results　No significant systemic toxicity was observed in ICR mice of either dosage group in 2 weeks, and the no observed adverse effect level (NOAEL) was 142.08 μg/d. The drug-related local irritant reaction was observed in 142.08 μg/d group, and the safe local dosage (71.04 μg/d) was 31.17 times of the clinical intended dose. The blood concentration of anti-SARS-CoV-2 IgY was under the lower limit of quantitation (0.74 μg/mL) in all SD rats of any dosage group, and no obvious systemic toxic reaction was observed. The NOAEL for SD rats (2 557.40 μg/d) was 112.20 times of the clinical intended dose, with only high-dosage group male rats presented a reversible local irritant response on nasal mucosa and tunica propria. Active skin allergic reactions in guinea pigs and eye irritation in New Zealand rabbits were both negative. Conclusions　The anti-SARS-CoV-2 IgY spray shows good safety when administered through the nasal cavity and oropharynx. At more than 100 times of human clinical highest intended dose, no obvious systemic toxicity occurs. The local irritant reaction observed in high-dosage group SD rats is recoverable. At clinical concentration, the tested product does not cause anaphylactic response in skin or irritate eyes.