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Chiến lược thử nghiệm tích hợp Bayesian (ITS) đánh giá độ nhạy cảm da: một hệ thống hỗ trợ quyết định cho trọng số bằng chứng định lượng và chiến lược thử nghiệm thích ứng
Tóm tắt
Hệ thống chiến lược thử nghiệm tích hợp Bayesian (ITS-3) được trình bày cho việc đánh giá độ nhạy cảm da là một hệ thống hỗ trợ quyết định dành cho người đánh giá rủi ro, cung cấp trọng số bằng chứng định lượng, dẫn đến một giả thuyết về độ nhạy cảm có thể giải thích theo cơ chế, và xây dựng chiến lược thử nghiệm thích ứng cho một hóa chất. Hệ thống này được xây dựng với mục tiêu cải thiện độ chính xác và độ chính xác trong việc dự đoán độ nhạy cảm LLNA vượt qua ITS-2 (Jaworska et al., J Appl Toxicol 33(11):1353–1364, 2013) bằng cách cải thiện đại diện của hóa học và sinh học. Những yếu tố mới bao gồm các điều chỉnh về độ khả dụng sinh học cả in vivo và in vitro cũng như xem xét miền áp dụng của các xét nghiệm riêng lẻ trong quá trình dự đoán. Trong cấu trúc ITS-3, ba bài thử nghiệm thay thế đã được xác thực, DPRA, KeratinoSens và h-CLAT, đại diện cho ba sự kiện chính đầu tiên của con đường kết quả bất lợi cho sự nhạy cảm da. Dự đoán độ nhạy cảm da được cung cấp dưới dạng phân phối xác suất trên bốn lớp độ nhạy cảm. Phân phối xác suất được chuyển đổi thành các yếu tố Bayes để: 1) loại bỏ thiên lệch dự đoán do phân phối độ nhạy cảm của tập đào tạo gây ra và 2) diễn đạt sự không chắc chắn theo cách định lượng, cho phép các tiêu chí minh bạch và nhất quán để chấp nhận một dự đoán. Cơ sở dữ liệu ITS-3 mới bao gồm 207 hóa chất với một bộ dữ liệu đầy đủ về in vivo và in vitro. Độ chính xác trong việc dự đoán kết quả LLNA trên tập kiểm tra bên ngoài (n = 60) như sau: mối nguy (hai lớp) - 100 %, phân loại độ nhạy cảm GHS (ba lớp) - 96 %, độ nhạy cảm (bốn lớp) - 89 %. Công trình này chứng minh rằng việc dự đoán độ nhạy cảm da dựa trên dữ liệu từ ba sự kiện chính, và thường là ít hơn, là khả thi, đáng tin cậy trên các lớp hóa chất rộng và sẵn sàng cho các ứng dụng thực tiễn.
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