The analysis was performed using gas chromatography-mass spectrometry (GC-MS) with an external standard method, based on Chinese National Food Safety Standards for foods [25, 26, 27] with modifications.

Briefly, standard solutions were prepared by diluting a mixed intermediate solution of 18 PAEs in n-hexane. For quantification, a suite of deuterated internal standards (ISTDs) was employed: D4-DMP, D4-DBP, and D4-DEEP, each at a concentration of 10 µg mL^-1. These ISTDs were selected based on their structural analogy and chromatographic behavior to represent different subgroups of the target PAEs: D4-DMP for short-chain dimethyl phthalate, D4-DBP for mid-chain dibutyl phthalate and its isomers (e.g., DIBP), and D4-DEEP for high-molecular-weight phthalates such as DEHP, DINP, and DIDP. This approach allows for effective correction of matrix effects and instrumental variability across the entire analyte range. Calibration standards contained these ISTDs at 0.5 µg mL^-1 (D4-DINP at 5.0 µg mL^-1 to match its higher typical concentration), with working ranges of 0.1–10 µg mL^-1 for DINP/DIDP and 0.01–1.0 µg mL^-1 for other PAEs. A fresh calibration curve was established prior to each batch of sample analysis, requiring the relative standard deviation (RSD) of the relative response factors for all calibration points to be 15%. A mid-level calibration verification standard was injected every 24 hours during continuous operation, with the deviation controlled within $\pm$20%. All calibration curves exhibited satisfactory linearity, with correlation coefficients (R²) greater than 0.998.

For sample preparation, 2.0 mL of Baijiu sample was transferred into a 10 mL glass tube. After spiking with 100 µL of internal standard solution, the ethanol content was adjusted to 20% (v/v) with ultrapure water to control matrix effects. Liquid-liquid extraction was then performed by adding 2 mL of toluene, followed by vortex mixing for 3 min and centrifugation at 3000 r/min for 5 min. The organic phase was analyzed using a GC-MS/MS system (Agilent 7890A - 7000B) equipped with a DB-5ms UI column (30 m $\times$ 0.25 mm, 0.25 µm). Helium was used as the carrier gas at a constant flow rate of 1.0 mL/min. The oven temperature program was as follows: initial temperature at 60 °C (held for 1 min), increased to 220 °C at 20 °C/min (held for 1 min), then to 280 °C at 5 °C/min (held for 10 min), and finally to 300 °C at 20 °C/min (held for 4 min). MS detection was performed in multiple reaction monitoring (MRM) mode using electron ionization (70 eV) with the ion source temperature set at 250 °C.

The detection of PAEs was conducted at reference laboratories for China’s national food safety risk monitoring system. This system operates under the Food Safety Law of China, with the National Health Commission (NHC) taking the lead in organizing the implementation of national monitoring plans. The technical execution, including food contamination monitoring and dietary exposure surveys, is primarily carried out by the China National Center for Food Safety Risk Assessment (CFSA) and the nationwide network of Centers for Disease Control and Prevention (CDC) at various levels (provincial, municipal, county). All personnel were trained, and all laboratories followed a unified analytical protocol before commencing analysis. Each batch of samples was analyzed alongside quality control (QC) samples, and formal sample testing began only after the QC data met predefined acceptance criteria. Any result that exceeded the corresponding regulatory limit was retested, and only the confirmed qualified data were used for the risk assessment. All procedures, including sample pretreatment, instrumental analysis, and standard preparation, were performed according to documented standard operating procedures (SOPs). Comprehensive quality assurance measures were implemented throughout the analytical process. Procedural blanks and reagent blanks were processed with each batch of samples (maximum 20 samples per batch) to monitor and account for any background contamination. All target PAEs in blank samples were confirmed to be below the method limits of detection (LODs). The accuracy and precision of the method were evaluated through matrix spike recovery experiments. Baijiu samples were spiked with standard solutions at low, medium, and high concentration levels (n = 6). The average recoveries for all target compounds ranged from 80% to 120%, with intra-day and inter-day relative standard deviations (RSDs) below 10%. The LODs were 0.3 mg kg^-1 for DBP, 9.0 mg kg^-1 for DINP, and the other 16 target compounds were 0.5 mg kg^-1. The limits of quantification (LOQ) were defined as 3.3 times the LOD for each compound.

According to the recommended procedure of “Reliable Evaluation of Low Level Pollutants in Food” issued by the World Health Organization (WHO), if the proportion of non-detected (ND) results is less than 60%, all the undetected value are substituted for 1/2 LOD; If the proportion greater than 60%, 0 and LOD values are substituted for the undetected value in statistical calculation [28]. In this study, for the purpose of statistical analysis, concentrations between the LOD and LOQ were treated as non-detects.

The daily intake of each PAE for each individual was calculated by multiplying their individual consumption data by the corresponding mean PAE concentration. From the distribution of these estimated individual exposures across all participants, the mean, 50th percentile (P50), 95th percentile (P95), and maximum exposure levels were derived for the overall adult population and for each demographic subgroup: females (18–59 years), males (18–59 years), females ($\ge$60 years), and males ($\ge$60 years).

The equation was as follows:

$$EX{P}_{\mathrm{i}}=\frac{C\times F_{\mathrm{i}}}{B{W}_i}$$

where EXPᵢ is the estimated daily intake of PAEs for consumer i (µg kg^–1 bw d^–1); C is the mean concentration of a given PAE in Baijiu (mg kg^–1); Fᵢ is the daily Baijiu consumption for consumer i (g d^–1); and BWᵢ is the body weight of consumer i (kg).

Based on their similar reproductive effects, EFSA grouped DBP, BBP, DEHP, and DINP for a cumulative assessment. Relative potency factors (RPFs) were allocated using DEHP as the reference substance to derive a group-TDI [22]. Accordingly, the aggregated dietary exposure to these phthalates was calculated by incorporating their respective RPFs, using the following equation:

$$EX{P}_{\mathrm{m}}=\sum _{i=1}^{n}EX{P}_i\times RP{F}_i$$

Where EXP_m is the cumulative PAEs intake adjusted by the RPFs (µg kg^-1 bw d^-1); EXP_i is the estimated intake of phthalate i (µg kg^-1 bw d^-1); and RPF_i is the RPF for phthalate i. Using DEHP as the reference substance, the RPFs for DEHP, DBP, BBP and DINP are 1, 5, 0.1 and 0.3, respectively [22].

The hazard quotient (HQ) for each PAE from Baijiu was calculated by dividing the estimated daily intake (EXP) by its corresponding TDI. The cumulative risk from exposure to multiple PAEs was assessed using the hazard index (HI) method. The HQ and HI were calculated as follows:

$$HI=\sum _{i=1}^{n}HQ=\sum _{i=1}^n\frac{EX{P}_i}{R{V}_i}$$

Where EXP_i is the estimated daily intake of the i-th type of PAEs (µg kg^-1 bw d^-1), and $R{V}_i$ is the corresponding health-based guideline value for the i-th PAEs (µg kg^-1 bw d^-1). An HI value $\le$1 indicates that the cumulative risk is considered acceptable, whereas an HI value $>$1 suggests a potential risk of concern for the target population [30].

Considering the relatively high PAE levels in these samples and the completeness of their toxicological data, the average daily intake of DEHP, DBP, BBP, DINP, DIBP, and DMP from Baijiu consumption was estimated for the general adult population ($\ge$18 years) in Sichuan Province. The dietary exposure assessment for these six phthalates revealed consistently low exposure levels, all well below their respective safety thresholds (Table 5).

Specifically, for DEHP, the mean and 95th percentile (P95) exposures were 0.003 and 0.021 µg kg^–1 bw d^–1, representing only 0.007% and 0.042% of its tolerable daily intake (TDI of 50 µg kg^–1 bw d^–1). Similar low-level exposures were observed for DBP (0.061 and 0.366 µg kg^–1 bw d^–1, accounting for 0.606 and 3.663% of its TDI of 10 µg kg^–1 bw d^–1) and BBP (0.003 and 0.021 µg kg^–1 bw d^–1, representing 0.001 and 0.004% of its TDI of 500 µg kg^–1 bw d^–1).

Notably, DINP was not detected in any samples, with estimated exposures below the limit of detection. For DIBP and DMP, which were assessed using the threshold of toxicological concern (TTC of 30 µg kg^–1 bw d^–1), exposures were also extremely low (0.017–0.101 and 0.011–0.068 µg kg^–1 bw d^–1, respectively), constituting less than 0.34% of the TTC.

Demographic analysis showed consistent trends across all compounds. The highest exposures occurred in men aged $\ge$60 years (e.g., 0.133 µg kg^–1 bw d^–1 for DBP), while the lowest were found in women aged 18–59 years (e.g., 0.001 µg kg^–1 bw d^–1 for DEHP) (Fig. 1). Collectively, these findings indicate that current dietary exposure to the assessed phthalates through Baijiu consumption in Sichuan Province poses negligible health risks, with all measured levels orders of magnitude below relevant safety thresholds.

3.3.2.1 HI Method

A comprehensive risk assessment for the six PAEs was conducted using the HI method. This included the four PAEs with established reproductive toxicity (DEHP, DBP, BBP, DINP) as well as DIBP and DMP. The results demonstrated that both the mean and 95th percentile (P95) HI values for cumulative exposure to these six PAEs remained below the safety threshold of 1 across all demographic groups studied (Table 6). Specifically, the highest mean HI value (0.016) was observed in males aged $\ge$60 years, while the lowest (0.003) was found in female consumers.

Table 6. HI of six PAEs of Baijiu consumption in different genders and age groups.

Group	N	HI				Consumers of HI $\ge$1
		Mean	P50	P95	Max
Female (18$\sim$59 years old)	2021	0.003	0.000	0.009	0.442	0
Male (18$\sim$59 years old)	1768	0.010	0.000	0.067	0.524	0
Female (60 years and above)	843	0.003	0.000	0.007	0.258	0
Male (60 years and above)	840	0.016	0.000	0.095	0.562	0
Overall adults	5472	0.007	0.000	0.044	0.562	0

HI, hazard index.

3.3.2.2 Relative Potency Factors (RPF) Method

Due to their shared reproductive toxicity endpoint, the cumulative exposure to DEHP, DBP, BBP, and DINP was assessed. As DINP was not detected in any sample, its exposure was estimated by substituting the limit of detection (LOD) for non-detect values. The mean and 95th percentile (P95) cumulative exposure levels for these four PAEs were 0.315 µg kg^-1 bw d^-1 and 1.904 µg kg^-1 bw d^-1, respectively (Table 7). These values are substantially below the group-TDI of 50 µg kg^-1 bw d^-1, representing only 0.631% and 3.808% of this threshold. Demographically, the highest mean cumulative exposure was observed in males aged $\ge$60 years (0.692 µg kg^-1 bw d^-1), while the lowest was in females aged 18~59 years (0.118 µg kg^-1 bw d^-1). A consistent trend of higher exposure was observed in older age groups across the population.

Table 7. Cumulative intake of four PAEs of Baijiu in different genders and age groups.

Group	PAEs intake (µg kg-1 bw d-1)a				%Group-TDI b	%Group-TDI c
	Mean	P50	P95	Max
Female (18$\sim$59 years old)	0.118	0.000	0.394	19.222	0.237	0.787
Male (18$\sim$59 years old)	0.451	0.000	2.910	22.783	0.902	5.819
Female (60 years and above)	0.127	0.000	0.315	11.213	0.254	0.630
Male (60 years and above)	0.692	0.000	4.145	24.420	1.384	8.289
Overall adults	0.315	0.000	1.904	24.420	0.631	3.808

^a Group Phthalates exposure expressed as DEHP equivalents (µg kg^-1 bw d^-1) = DEHP $\times$ 1 + DBP $\times$ 5 + BBP $\times$ 0.1 + DINP $\times$ 0.3;

^b %Group-TDI was the percentage of mean PAEs intake to TDI (50 µg kg^-1 bw d^-1);

^c %Group-TDI was the percentage of P95 PAEs intake to TDI (50 µg kg^-1 bw d^-1).

However, these results must be interpreted with caution, as they reflect exposure solely from Baijiu and do not account for contributions from other dietary sources. Hence, a comparative analysis with existing literature—which often reports PAEs total dietary exposures—will be presented in the following paragraph to contextualize our findings within the overall exposure scenario.

3.3.2.3 A Specific Adjusted Group-TDI Method

However, single-source assessment does not fully capture cumulative total dietary risk. Baijiu-derived PAEs to total dietary PAE exposure and the corresponding health risk assessment results were accounted. Based on established total dietary exposure estimates [10, 22], the total dietary exposure levels of PAEs were as follows: DEHP (2.23 µg kg^-1 bw d^-1), DBP (2.35 µg kg^-1 bw d^-1), BBP (1.00 µg kg^-1 bw d^-1), and DINP (1.81 µg kg^-1 bw d^-1). Thus, the single exposure contribution rates of DEHP, DBP, BBP, and DINP from Baijiu were calculated to be 0.16%, 2.58%, 0.35%, and 1.52%, respectively, with a cumulative exposure contribution rate of 2.16%. By reallocating the TDI based on these contributions, adjusted TDIs for DEHP, DBP, BBP, and DINP were determined to be 0.07, 0.26, 1.73, and 2.28 µg kg^-1 bw d^-1, respectively. The adjusted group-TDI value was calculated as 1.08 µg kg^-1 bw d^-1. Consequently, the mean (0.315 µg kg^-1 bw d^-1) and P95 (1.904 µg kg^-1 bw d^-1) exposures from Baijiu represented 29.25% and 176.63% of this adjusted group-TDI, respectively. This indicates a potential risk for high-consumption individuals, underscoring the importance of moderate alcohol intake.