An updated weight of evidence approach for deriving a health‐based guidance value for 4‐nonylphenol

Abstract

4-Nonylphenol (NP) is a persistent estrogen-active compound. Human exposure to NP is primarily through water and food. Although risk assessments of NP have been conducted by the European Union and a few other countries, only the Danish Veterinary and Food Administration, in 2000, proposed a tolerable daily intake of 0.005 mg kg body weight (bw) day . New data have been accumulated since then, prompting an update on the risk assessment of NP. A weight of evidence approach is recommended for use in scientific assessments by several agencies, e.g., European Food Safety Authority, etc. Based on the results of a weight of evidence approach, two methods were used to derive the health-based guidance value (HBGV) for NP in this study, namely a no observed adverse effects level/lowest observable adverse effect level method, and a benchmark dose method. Considering the considerable uncertainty of benchmark dose model fitting of the available data, a tolerable daily intake value of 0.025 mg kg bw day was derived as a provisional HBGV for NP based on the lowest observable adverse effect level value of 15 mg kg bw day of the renal toxicity in rats, together with the uncertainty factor of 600. However, the HBGV of NP still needs further investigation.

Effects of atrazine on fish, amphibians, and reptiles: update of the analysis based on quantitative weight of evidence

“…The results of that exercise were published (Van Der Kraak et al 2014) and accompanied by an extensive and detailed assessment of the included studies in the Supplemental information (SI). Previous uses of the WoE framework were summarized in Van Der Kraak et al (2014) and since that time, the concept has been used or recommended in papers and by regulators conducting human and ecological risk assessments (Becker et al 2015(Becker et al , 2017Lutter et al 2015;Rhomberg 2015;Acquavella et al 2016;Agerstrand and Beronius 2016;Bridges and Solomon 2016;Brusick et al 2016;Collier et al 2016;EFSA 2017;Gross et al 2017;LaLone et al 2017;Møller and Jacobsen 2017;Stevenson and Chapman 2017;Suter et al 2017;Li et al 2019;Martin et al 2018;Rocca et al 2018;Rycroft et al 2018).…”

Filling the blank space: Branched 4-nonylphenols isomers are responsible for robust constitutive androstane receptor (CAR) activation by nonylphenol

“…Nonylphenol is widely used in food packaging, hair dyes, other personal care products, textile printing and dyes, pesticides and other agricultural-related substances, and non-ionic surfactants. Owing to its low solubility, NP is prone to accumulate in environmental matrices, such as in water, soils and sediments (Li et al, 2019). Nonylphenol's widespread presence in the environment is illustrated in a study that found NP to be one of three groups of organic wastewater contaminants that together contributed to almost 80% of the total measured concentration of organic wastewater contaminants in U.S. streams (Kolpin et al, 2002).…”

“…NP is also known to act in the hippocampus and frontal cortex resulting in impaired cognitive function due to induced inflammatory and apoptotic processes and interfering with neurotransmission secretion (Lu et al, 2021b). Despite NP's overall relevance, a health-based guideline value has yet to be internationally established (Chung, 2021;Li et al, 2019). CAR nuclear receptor is one of the main drug-and xenobiotic-responsive transcription factors regulating the expression of detoxification enzymes, conjugation enzymes and transporters involved in the elimination of endogenous and exogenous substances, such as bilirubin, bile acids, and xenobiotics (di Masi et al, 2009;Kublbeck et al, 2020a).…”