Rare earth elements (REEs) are abundant in the earth's crust and commonly found in the environment, in electronics, medicine, agriculture, animal husbandry, and daily life[1], [2], [3], and dust, tap water systems, and human food supply chains[4], [5], [6], [7]. In recent years, the gradual increase in mining and application of REEs has caused environmental pollution worldwide. China, a large supplier of rare earth and a major consumer is facing a huge problem of rare earth pollution[8], [9], [10], [11]. The main routes of entry of REEs into the human body are the respiratory tract and oral cavity, followed by skin contact and intestinal absorption[10]. In reality, humans ingest REEs mainly through consuming contaminated food and water, occupational exposure, and using some medical devices[12], [13], [14]. Therefore, there is an urgent need for more attention and further research on the effects of exposure to REEs on human health.

It has been shown that exposure to REEs increases the concentration of REEs in body organs and tissues[15], [16]. Moreover, accumulation of REEs has been observed in various human organs[17]. It has also been found that oral administration of CeCl3 to male mice by gavage for 90 consecutive days observed cerium accumulation, liver inflammation and stem cell necrosis[18]. It has also been found that in the tissues of animals such as Canada Goose, Arctic Cod, and Bearded Seal, the average concentration of REEs detected in the liver were all higher than in muscle and bone[19]. Therefore, we initiated a study of the effects of REEs on the liver.

Liver diseases have a very high prevalence in the population and are one of the leading causes of disease and death worldwide. Previous studies have focused more on liver diseases caused by pathological factors, such as various viral hepatitis. However, increasing numbers of studies have proved that hepatocyte exposure to harmful environmental pollutants such as heavy metals can cause liver dysfunction, liver cell damage, and organ failure[20], [21], [22], [23], [24]. A cross-sectional study in the United States has shown that long-term exposure to cadmium is positively associated with liver damage[25], and a population-based study from Korea has demonstrated that exposure to lead, cadmium, and mercury is correlated with liver damage[26]. Previous studies have shown that rare earth elements, as a kind of metal, may also be related to liver damage. Mathieu Desrosiers et al. found that REEs are easily removed from the blood and accumulate mainly in the liver[27]. Grajewski O et al. suggested that light REEs can make the liver more susceptible to fat storage, causing fatty liver and leading to metabolic disorders[28]. In an animal experiment using mice as research subjects, it has been found that gavage of dyed CeCl3 (2 mg/kg) for 90 consecutive days can result in liver inflammation, apoptosis, and other liver damage in mice[18]. Ln3+ at a dose of 20 mg/kg induces structural damage and fatty degenerative effects in mouse liver cells, causing liver dysfunction, while Ce3+ causes stronger hepatotoxicity than La3+ and Nd3+[29]. The accumulation of five REEs, La, Ce, Pr, Nd, and Gd, in Sprague-Dawley (SD) rats' blood and hair is reversible to low concentrations. However, the accumulation of these five REEs in the liver, spleen, and bone is irreversible[30]. In addition, it has been found that long-term exposure to Ln can cause pathological changes in the liver of rats and damage to its function, such as liver cell necrosis and basophilia[31].

Detecting the health effects of exposure to chemical mixtures is becoming increasingly important, and in response to this need, a variety of statistical methods have been developed to assess the relationship between individual chemical exposures, as well as mixed exposures, and health outcomes[32], including weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR).

The correlation between exposure to REEs and liver function is currently understudied, and although a number of studies have been conducted to show the close association between REEs and the liver, the evidence from these studies is largely derived from cellular or animal experiments, and there is a lack of evidence support from population studies. We hypothesized that REEs could also have an effect on liver function in humans. Therefore, we conducted an epidemiologic study in the population to further investigate the possible effects of REEs exposure on the liver by measuring the concentration of REEs in the urine of the Zhuang population in the Nanning area, and evaluating the relationship between REEs exposure and liver function indices using the WQS and BKMR models.