B-189 Evaluate the suitability of urinary reference intervals for organophosphate flame retardants in healthy adult population from Southern Taiwan
Authors: Chen C M , You H L , Huang W T 
Published: September 2023

Abstract

Background
Organophosphorus flame retardants (OPFRs) are chemical additives used to prevent fires and are widely used in furniture, electronics, plastics, and building materials. Its chemical structure is similar to human hormones, which are often misidentified and used in the human body, thereby interfering with the operation of normal physiological functions and causing endocrine system disorders, so it is also known as environmental hormones. Recently, it has been confirmed that exposure to OPFRs can cause health hazards such as neurotoxicity, endocrine disruption, hepatotoxicity, and reproductive dysfunction. In view of the increasing concern about the exposure of human OPFRs, but there is no laboratory in Taiwan to detect the content of human OPFRs. This study aims to develop a biomonitoring method for OPFRs, which is used to provide reliable information on the exposure status of individual OPFRs, and to establish a reference interval for OPFRs in the urine of different diseases and reference groups and confirm the potential of OPFRs as biomarkers in environmental medicine.

Methods
The Waters ACQUITY UPLC I-Class and Xevo TQ-XS IVD systems were developed to detect 10 OPFRs in urine: Tri-(n-butyl) phosphate (TNBP), Tris-(2-butoxyethyl) phosphate (TBEP), Tris-(1,3- dichloro-2-propyl) phosphate (TDCPP), Triphenyl phosphate (TPHP), Tris-(2-chloroethyl) phosphate (TCEP), Di-n-butylphosphate (DNBP), Bis-(butoxyethyl)-Phosphate (DBEP), Bis-(1,3-dichloro-2-propyl) phosphate (BDCPP), Diphenyl phosphate (DPHP), Bis (2-chloroethyl) phosphate (BCEP), and analytical methods. According to the CLSI C62A specifications, the methodology verification and confirmation passed the evaluation. A total of 538 patients (78 infertility, 167 hemodialysis, 96 esophageal cancer, 99 lung cancer and 98 endometrial cancer) and 175 reference groups were tested for urine samples. The ANOVA analysis was used to compare the differences in the content of 10 OPFRs compounds in the urine of subjects of different ethnic groups. ROC curve analysis was used to determine the best decision value of whether the disease was present, and Chi-square verification was used to conduct disease risk assessment and verify the feasibility of the set reference value.

Results
The BCEP (6.23 ± 2.19 ng/mL) of most patients with hemodialysis, lung cancer and esophageal cancer was significantly higher than the reference group (0.89 ± 0.38 ng/mL). Patients with gynecological diseases had a higher BDCPP (4.29 ± 1.97 ng/mL) than the reference population (0.76 ± 0.32 ng/mL), which was consistent with the conclusions of previous animal experiments. Since it is not easy to explain the direct correlation between OPFRs and the disease. We decided to sum the detection values of 10 OPFRs. We found that their sum was greater than 2.05 ng/mL. The risk of infertility was 37.8 (95% CI: 11.07–129.14), the risk value of esophageal cancer was 83.3 (95% CI: 25.25–274.85) and the risk value of severe chronic kidney disease was 56.7 (95% CI: 17.49–183.97).

Conclusion
Due to the different types of OPFRs used in different countries, it is impossible to directly apply the reference values of other countries to their own people. So we develop the OPFRs detect method and verify the reference values through a series of analysis and discussion. Which will help us further understand the association between these environmental hormones and diseases.