# Using Eye Tracking to Evaluate Cognitive and Visual Outcomes of Early Life Phenol Exposure

Matthieu Rolland, Sadia Khan, Sarah Lyon-Caen, Cathrine Thomsen, Amrit Sakhi, Séverine Valmary-Degano, Azemira Sabaredzovic, Sam Bayat, Rémy Slama, David Méary, et al.

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## To cite this version:

Matthieu Rolland, Sadia Khan, Sarah Lyon-Caen, Cathrine Thomsen, Amrit Sakhi, et al. Using Eye Tracking to Evaluate Cognitive and Visual Outcomes of Early Life Phenol Exposure. Environmental Research, 2025, 282, pp.122067. 10.1016/j.envres.2025.122067. hal-05117375

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1 Using Eye Tracking to Evaluate Cognitive and
2 Visual Outcomes of Early Life Phenol Exposure

3

4 **Authors:** Matthieu Rolland¹, Sadia Khan¹, Sarah Lyon-Caen¹, Cathrine Thomsen², Amrit K.

5 Sakhi², Séverine Valmary-Degano³, Azemira Sabaredzovic², Sam Bayat⁴, Rémy Slama¹,

6 David Méary⁵, Claire Philippat¹

7 **Affiliations:**

8 ¹ University Grenoble Alpes, Inserm U-1209, CNRS-UMR-5309, Environmental

9 Epidemiology Applied to Reproduction and Respiratory Health Team, Institute for Advanced
10 Biosciences, 38000, Grenoble, France

11 ²Norwegian Institute of Public Health, Oslo, Norway

12 ³BB-0033-00069 Biobank, Univ. Grenoble Alpes, Inserm U1209, CNRS UMR5309, Institute
13 for Advanced Biosciences, CHU Grenoble-Alpes, F-38000 Grenoble, France

14 ⁴Department of Pulmonology and Physiology, CHU Grenoble Alpes, Grenoble, France

15 ⁵Laboratoire de Psychologie et Neurocognition, LPNC, UMR 5105, Université Grenoble
16 Alpes, Grenoble, France

17 **Corresponding author**

18 Claire Philippat

19 Institut pour l'Avancée des Biosciences, Centre de Recherche UGA / Inserm U 1209 /
20 CNRS-UMR 5309
21 Equipe d'épidémiologie environnementale appliquée au développement et à la santé

22 respiratoire

23 Site Santé – Allée des Alpes

24 38700 La Tronche

25 France

26

27 Contributors Statement Page

28

29 Matthieu Rolland: formal analysis, visualization, writing – original draft

30 Sadia Khan: writing – original draft

31 Remy Slama: review and editing, resources, cohort design

32 Sarah Lyon-Caen: review and editing, resources, data collection

33 Cathrine Thomsen: review and editing, chemical assessments

34 Amrit K. Sakhi: review and editing, chemical assessments

35 Azemira Sabaredzovic: review and editing, chemical assessments

36 Sam Bayat: review and editing, resource

37 Séverine Valmary-Degano: review and editing, resource

38 David Meary: review and editing, eye tracking assessments

39 Claire Philippat: writing – original draft, funding acquisition, scientific supervision, resource

40

41 All authors approved the final manuscript as submitted and agreed to be accountable for all

42 aspects of the work.

43

44
45 **Abstract**

46 **Introduction:** Studies on behavioral effects of synthetic phenols have often relied on parent-47 reported questionnaires and primarily focused on prenatal exposure.

48 **Aims:** We examined associations between prenatal and infancy phenol exposures and 49 objective measures of child visual behavior and cognitive function at 2 years of age.

50 **Methods:** At age 2, 151 children from the SEPAGES mother-child cohort completed eye-51 tracking tasks assessing four indicators: fixation duration (attentional control), novelty 52 preference (visual recognition memory), time spent looking at eyes (social attention), and 53 reaction time (processing speed).Phenol concentrations (two bisphenols, three parabens, 54 benzophenone-3, triclosan) were measured in multiple urine samples collected from mothers 55 (second and third trimesters; median: 42 samples per woman) and infants (2 and 12 months; 56 median: 7 samples).

57 **Results :** No associations were found with Σparabens. However, individual parabens showed 58 significant associations: ethylparaben at third trimester (T3) and 12 months (M12) was linked 59 to shorter reaction time; at 2 months (M2), it was associated with reduced time spent looking 60 at eyes. Propylparaben at T2 and T3 correlated with increased time spent looking at a novel 61 face, especially in boys. Bisphenol S at T2 was associated with reduced reaction time; at 62 M12, infants with detectable bisphenol S was linked to more time spent looking at eyes.

63 **Conclusion:** Several associations observed indicate that increased phenol exposure 64 sometimes correlated with improved eye-tracking scores. These findings align with prior 65 literature on phenol exposure and ASD symptoms, which highlight variability by exposure 66 window and phenol type.Given limited research and typically small sample sizes, further 67 studies using objective markers and clinical assessments are necessary.
69 **Keywords**

70 Phenol, Parabens, Infancy, Eye-Tracking, Cognition, Neurodevelopment, Exposure

71 **Abbreviations**

72

73 EDCs - Endocrine-disrupting chemicals

74 ASD - Autism Spectrum Disorders

75 CBCL - Child Behavior Checklist

76 SRS - Social Responsiveness Scale

77 SDQ - Strengths and Difficulties Questionnaire

78 MDI - Mental Development Index

79 LOD - Limit of detection

80 LOQ - Limit of quantification

81 WAIS-IV - Wechsler Adult Intelligence Scale – Fourth Edition

82 K-CPT2 - Conners Kiddie Continuous Performance Test

83 HPLC-MS-MS - High-performance liquid chromatography coupled with mass spectrometry

84 SEPAGES - Assessment of Air Pollution Exposure during

85 Pregnancy

and Effect on Health

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# 1. Introduction

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Despite some synthetic phenols being recognized as endocrine disruptors (Demeneix, 2019); they remain widely present in consumer products, leading to widespread exposure across the general population, including pregnant women and young children (Casas et al., 2013; Dereumeaux et al., 2016; Rolland et al., 2020). This is a public health concern because many health outcomes are closely linked to the endocrine system function. Child neurodevelopment, in particular, is a critical process that depends on hormonal homeostasis during prenatal and early postnatal life and even minor disruptions to this balance can be associated with neurodevelopmental disorders (Gore et al., 2014).

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Synthetic phenols can disrupt key hormonal and neurotransmitter pathways—including thyroid hormone signaling, estrogen receptor activity, and dopaminergic systems—essential to neurogenesis, neuronal migration, and synaptogenesis (Diamanti-Kandarakis et al., 2009; Gore et al., 2014; Rice and Barone, 2000). Disruptions during critical periods may impair the maturation of circuits involved in cognition, attention, and social behavior (Stiles and Jernigan, 2010).

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Both animal and epidemiological studies have suggested impaired cognitive function and behavior following prenatal exposure to some synthetic phenols. In rodents, prenatal exposure to bisphenol A has been associated with decreased investigation and interaction behaviors (Butler et al., 2020; Kaur et al., 2020; Repouskou et al., 2020) as well as increased repetitive behaviors (Butler et al., 2020).

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Several human studies have examined the relationship between prenatal phenol exposure and neurodevelopmental outcomes in early childhood. Most have focused on bisphenol A and reported associations with social impairments and increased behavioral problems (Braun,
119 2017; Evans et al., 2014; Hansen et al., 2021b; Lim et al., 2017; Liu et al., 2021; Maserejian
120 et al., 2012; Miodovnik et al., 2011; Pan et al., 2019; Philippat et al., 2017; Roen et al., 2015).

121 Results were mixed for the other phenols, with studies reporting null (Philippat et al., 2017)
122 or even protective associations (Etzel et al., 2018) depending on exposure timing and sex.

123 With few exception (Cragoe et al., 2024), most studies used tests done by neuropsychologist
124 to evaluate cognitive function (i.e. Bayley Scale of Early Learning, Wechsler Scale of
125 Intelligence) or parent-reported scales such as the CBCL or SRS to evaluate behavior, which
126 are subjective and may be prone to bias (Rosenman et al., 2011; Ross et al., 1995; Wilson et
127 al., 2000).

128 To overcome these challenges, eye-tracking offers a non-invasive and objective method to
129 assess attentional and cognitive processes from early infancy, with implementation possible
130 as early as 3 months of age. It has demonstrated sensitivity to subtle, subclinical patterns
131 across domains such as attention, social orientation, memory, and processing speed. Eye-
132 tracking has been used to detect early atypical visual behaviors in infants who were later
133 diagnosed with neurodevelopmental disorders such as ASD, including reduced time spent
134 looking at eyes and altered gaze patterns, both in clinical and at-risk populations (Elsabbagh
135 et al., 2013; Joseph et al., 2009a; Klin et al., 2002, 2002; Oakes, 2012; Sasson and Elison,
136 2012a; Telford et al., 2016; Wan et al., 2018; Yurkovic et al., 2021). However, most
137 epidemiological studies still rely on parent-reported outcomes and often lack postnatal
138 exposure data, despite infancy being a critical window of rapid brain development, as
139 highlighted in our previous findings (Mustieles et al., 2023; Rolland et al., 2023).

140 Given the scarcity of studies on early postnatal exposure and objective assessments of child
141 behavior at a young age, we aim to assess the associations between seven synthetic phenols
142 measured in repeated urine samples collected during pregnancy and the first year of life, and
143 behavioral indicators derived from eye-tracking tasks performed at 24 months. To our
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knowledge, this is one of the first studies in environmental epidemiology to combine repeated
exposure assessment across both prenatal and early postnatal windows with eye-tracking-
based outcomes in early childhood.

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## 2. Methods

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### 2.1 Study Population

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The study sample consisted of mother-child pairs from the French SEPAGES cohort recruited
in the Grenoble area between July 2014 and July 2017 (Lyon-Caen et al., 2019). Eligibility
criteria included: being less than 19 weeks pregnant at enrollment, over 18 years old, fluent in
French, affiliated with the national social security system (i.e., to ensure access to standard
care and reimbursements) and planning to deliver in one of the four area's maternity clinics.

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Multiple pregnancies were excluded. Out of the 484 women enrolled in SEPAGES, this
project was restricted to 151 infants whose parent agreed to participate in the eye tracking
sub-study, and for whom both eye-tracking measurement at 24 months and phenol
exposure data during pregnancy or infancy were available (Figure 1). The relatively limited
sample size for the eye-tracking sub-study can be partly explained by a delayed setup
(starting in September 2017, while SEPAGES children began turning two in January 2017)
and scheduling constraints in the laboratory, which reduced the number of eligible families
who could be tested within the targeted age window. The study received ethical approval
from the Comité de Protection des Personnes (CPP) Sud-Est V (approval number: 13-CHUG-
44), and authorization from the French Data Protection Authority (Commission Nationale de
l'Informatique et des Libertés, CNIL). Written informed consent was obtained from both
parents.
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## 2.2 Urine Sample Collection and Exposure Assessment

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Urine samples were collected from the mothers during the second and third trimesters of pregnancy, and from their infants at 2 and 12 months postnatally. During pregnancy, women were instructed to collect three spot urine samples per day—morning (first void), midday, and evening (last void before bedtime)—over seven consecutive days for each collection period. For infants, one urine sample per day was collected over seven days at each time point, without constraints on timing, to avoid contamination with stool. Infant urine was collected using cotton pads placed inside the diaper. These samples were pooled per participant and per period, resulting in four urine pools per mother–child pair. Aliquotes of these pooled samples were stored at -80°C in Grenoble University Hospital Biobank (bb-0033-00069), and shipped on dry ice to the Norwegian Institute of Public Health (NIPH) and analyzed for phenol concentrations using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS-MS) (Sakhi et al., 2018). Total concentrations of 7 phenols were measured including 2 bisphenols, 3 parabens, benzophenone 3 and triclosan.

The phenol analysis method is fully validated, and inter- and intra-assay variabilities were below 25% for most of the phenols (Sakhi et al. Levels, variability and determinants of environmental phenols in pairs of Norwegian mothers and children. Environment International 114 (2018) 242–251). For quality assurance, two procedural blank samples, two in-house control samples and one external control sample (standard reference material (SRM 3673) from the National Institute of Standards and Technology (NIST) were analyzed along with each batch/sequence of 50 samples. Potential contamination through sampling material was assessed and found negligible (Rolland et al., 2020). However, contamination of infant urine samples with free bisphenol A and free methylparaben was observed, most likely due to the use of diapers. To address this, we exclusively used the conjugated (i.e., metabolized) forms of bisphenol A and methylparaben in all analyses. For the other phenols, total
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concentrations (sum of free and conjugated forms) were used. Specific gravity was measured
in each pooled sample using a handheld refractometer (Atago PAL 10-S, Atago Co., Japan).

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To reduce measurement error, concentrations were preprocessed following a two-step
approach: values below LOD were imputed using distribution-based methods (Helsel, 1990),
and concentrations were standardized to account for analytical batch effects and sample
handling conditions (Mortamais et al., 2012; Rolland, 2025).

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## 2.3 Eye Tracking Assessment

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Eye movements were recorded using an Eyelink 1000 system (SR Research, Ontario) at 250 Hz, or 500 Hz for the saccadic task. Data were captured in head reference mode using a 16mm lens for infant studies and a target sticker for head-free tracking. A 940 nm illuminator was used for infants. The Eyelink system offers 0.5° accuracy, a tracking range of 32° (horizontal) x 25° (vertical), and accommodates head movements within a 22x18x20 cm area.

Stimuli were displayed on a monitor (Iiyama Vision Master Pro 514, 40.5 x 30.5 cm, 1024 x 768 pixels). Fixations (pauses at a location for at least 80ms) and saccades (rapid movements lasting 10-60ms) were identified using the Eyelink parser with predefined parameters (acceleration ≥ 8000°/s², velocity ≥ 30°/s, position change >0.15°).

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During testing, infants sat on their parent's lap at a distance of 520-580 mm from the screen.
The experiments were conducted in low-light, standardized conditions with distractions
minimized by an occluding curtain. A target sticker placed on the infant's forehead served as
a reference point for head tracking. Either the right or left eye was tracked, depending on
signal quality. Calibration was performed using a 5-point procedure with custom audiovisual
targets, ensuring calibration-validation errors were below 1°. Each trial began only after the
infant fixated on an attention grabber (positional error < 2°).

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215 Infants completed four tasks: (1) scene exploration, (2) visual paired recognition with faces, (3) saccade-to-target, and (4) smooth pursuit (See Supplementary Material, Table S1 for details on the tasks).

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219 The primary outcomes derived from those tasks were:

220 1) the mean fixation durations (in milliseconds, ms) serve as an indicator of attentional control and were obtained from two tasks: the visual paired recognition task with faces and the scene exploration task. Shorter mean fixation durations in infancy have been observed in children with ASD (Al-Haddad et al., 2020; Joseph et al., 2009a; Sasson and Elison, 2012b; Wan et al., 2019; Wass et al., 2015) and have been linked to higher scores of hyperactivity-inattention (Papageorgiou et al., 2014)

226 2) novelty preference (%) corresponded to the percentage of time spent looking at a novel face. It was derived from the visual paired recognition task with faces. This measure reflects recognition/visual memory rather than processing speed. It has been shown to predict intellectual quotient scores at 6 and 11 years (Rose et al., 1992; Rose and Feldman, 1995) as well as the mental development index scores on the Bayley Scale of Early Learning (BSID) at 3 years (Rose et al., 2009).

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233 3) percent time spent looking at the eyes (%): the proportion of time spent gazing at the eyes was obtained from the visual paired recognition task using faces. This metric has been employed in autism research, with findings indicating that individuals with autism often exhibit reduced eye contact starting as early as 6 months (Jones and Klin, 2013).

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4) The mean reaction time (ms) was calculated from two tasks: the saccade to target task and the smooth-pursuit task. This measure reflects the child's ability to shift attention from one location to another, serving as an indicator of processing speed. Shorter reaction times during infancy have been associated with higher IQ scores in later years (Thomas M Dougherty and Haith, 1997). Of interest, infants with ASD have shown superior performance in visual search tasks, with reaction times that are faster than those of typically developing children (Joseph et al., 2009b).

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The sample size slightly varied across scores as a few children did not perform all four tasks (Table 1).

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## 2.4 Statistical Analysis

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### *Exposure and outcome data pre-processing*

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Phenol concentrations below the limit of detection and quantification were singly imputed using the compound's probability distribution (Helsel, 1990). For compounds with more than 30% of samples below the LOD (butylparaben and bisphenol S), concentrations were categorized as detected or undetected (Lubin et al., 2004). Concentrations were ln-transformed for analysis. When needed, urinary concentrations were standardized for sampling (sample transportation time between the participant's home and the biobank and sample thawing time during the pooling procedure) and analytical conditions (analytical batch) (Guilbert et al., 2021; Mortamais et al., 2012), See Supplementary Material for details on this standardization. Additionally, the molar sum of parabens was calculated and included in the analysis.
261 With the exception of mean fixation duration, which was ln-transformed to normalize its distribution, all other eye-tracking scores were used in their original scale in the models.

263 **2.5 Covariates**

264 Candidate model covariates included factors that were likely to be associated with both
265 phenol exposure and eye-tracking scores, without being influenced by them, as well as
266 potential predictors of eye-tracking scores only. These were selected based on prior literature,
267 theoretical considerations, and the causal structure outlined in a Directed Acyclic Graph
268 (Figure S1). Regression models including all candidate covariates and excluding exposure
269 were performed for each eye-tracking score. A covariate was retained in all final models if its
270 p-value was less than 0.2 in at least one of the models. This selection criterion was applied
271 due to the relatively small sample size.

272 The final set of covariates included in all the models was: maternal age (continuous, linear),
273 maternal tobacco consumption after conception (Yes/No), maternal cognitive function
274 assessed with the verbal component of the Wechsler Adult Intelligence Scale – Fourth
275 Edition (WAIS-IV, continuous, linear), parity (1st child/2nd child/3rd child or more),
276 maternal professional status at sampling time (working, not working and not looking for
277 work, not working and looking for work), breastfeeding duration (continuous, linear), child
278 sex (male/female), and experiment time of the day (continuous, 4-degree natural spline). The
279 considered covariates that were not retained were: maternal education, gestational age at
280 birth, child age at assessment, and maternal depression (Table S2).

281 Linear regression models were used to study the associations between phenol concentrations
282 and continuous scores (i.e., fixation duration and reaction time), while beta regression models
283 were applied to percentage scores (i.e., time spent looking at eyes and novelty preference).
Regarding model interpretation, betas are provided for an increase by one in the ln-transformed concentrations, except for mean fixation duration for which betas represent the percent change in fixation duration for doubling in biomarker concentration.

## 2.6 Interaction Analysis

Given that previous studies have suggested effects modification by child sex for phenol exposure (Hansen et al., 2021a; Lim et al., 2017), we performed additional analyses where we included an interaction term between phenol concentrations and child sex. A p-value for the interaction term below 0.2 was considered as an indication of potential effect modification, leading us to perform further analyses stratified by sex.

## 2.7 Interpretation of results

Although we set the significance threshold at a p-value of <0.05, our interpretation of results was not based solely on statistical significance. Given our relatively small sample size, and exploratory setting (among the first study with phenol exposure and eye tracking scores) p-values between 0.05 and 0.10 were considered suggestive of an association if they aligned with a consistent pattern of results, rather than being isolated findings.

## 2.8 Sensitivity Analysis

The following sensitivity analysis were performed for the uni-pollutant models

1. Data points falling below the <1st and above the >99th percentiles for the exposures and outcomes were removed across each model. This was done to rule out artefact from extreme values.

2. We also performed the analysis using unstandardised concentrations of the exposures (i.e. not standardized for sampling and analytical conditions).
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3. We repeated all models using specific gravity-standardized concentrations, in place of raw values, to account for urinary dilution.

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All tasks and eye-tracking data postprocessing were conducted using MatLab (R2007b) and the Eyelink® toolbox, while statistical analyses were carried out using R version 4.2.0 (R Core Team, 2021). The R code is available at : https://gricad-gitlab.univ-grenoble-alpes.fr/iab-env-epi.

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## 3. Results

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### 3.1. Study Population

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Median age of the mothers at enrollment was 32.1 years (IQR: 4.8). Male children were slightly overrepresented in our study (N = 85, 56%) and majority of the mothers were highly educated (N=130, 86% had 2 years of studies or more after graduation). No major differences were observed between included and excluded pairs in maternal or child characteristics, except for maternal ethnicity (included were 92% European VS 79% for non included) (Table 1).

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### 3.2. Eye Tracking Scores

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Eye tracking assessments (81%) were mostly performed in the morning (between 8 AM and 12 PM) and the median age of the children was 24.9 months (IQR: 0.82) (Table 1). Spearman correlation coefficients for the eye tracking scores were below 0.2 (Supplementary Material, Table S3).

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### 3.3. Exposure

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The detection rates for most phenols were generally high, with methylparaben, bisphenol A, and benzophenone-3 detected in over 90% of samples (Table 2). Exposure levels were
328 notably lower at the 2-month infant sampling period, with detection rates below 90% for
329 ethylparaben and propylparaben, which may result from over dilution since the median SG
330 for 2 months samples (M2) was 1.004 whereas median SG for second trimester (T2), third
331 trimester (T3) and 12 month (M12) was > 1.011 (Table 1). Bisphenol S was detected in only
332 28% of samples during the second trimester, 30% during the third trimester, 46% at 2
333 months, and 70% at 12 months (Table 2).

334 **3.4. Adjusted Associations between Phenol Exposure and Eye Tracking Scores**

335 *Parabens*

336 While no association was observed with Σparabens, several associations were observed with
337 individual parabens. Ethylparaben concentration at T3 and M12 was associated with
338 decreased reaction time (β = -4.4 ms [-9.4, 0.5] and β = -2.7 ms [-6.0, 0.5] respectively). At
339 M2, this paraben was also associated with reduced time spent looking at the eyes (β = -7.8%
340 [-14.4,-1.2]) (Figure 2, Supplementary Material, Table S4).

341 Methylparaben concentration at M2 was negatively associated with the percentage of time
342 spent looking at a novel face (β = -1.9% [-3.8, -0.1]).

343 Propylparaben concentration at both T2 and T3 was associated with increased time spent
344 looking at a novel face (β = 1.9% [-0.0, 3.9] and β = 1.5% [-0.1, 3.3]). At T3, this trend was
345 driven by boys (β = 2.9% [0.7, 5.1] VS β = -0.4 [-3.1, 2.3] for girls) (Figure 2 and 3,
346 Supplementary Material, Table S4-5).

347 Sex stratification also revealed an association between the Σparabens and reduced fixation
348 duration in boys at T3 (β = -1.8ms [-3.4, -0.1]). This association was also observed at the
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individual compound level for methylparaben and propylparaben ($\beta$ = -1.7ms [-3.3, -0.1] and -0.9ms [-1.8, 0.0], respectively) (Figure 2 and 3, Supplementary Material, Table S4-5).

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*Bisphenols*

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No associations were observed with bisphenol A. Bisphenol S detection at T2 was associated with reduced reaction time ($\beta$ = -16.0 ms [-31.9, -0.1]) (Figure 2, Supplementary Material, Table S4).

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*Benzophenone-3*

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Benzophenone-3 concentrations at M2 and M12 were associated with increased time looking at a novel face ($\beta$ = 5.6% [1.5, 9.8] at M2 and $\beta$ = 5.5% [-1.0, 12.0] at M12). These associations were mainly seen in boys (Figure 2 and 3, Supplementary Material, Table S4-5).

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*Triclosan*

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An isolated association was observed between triclosan exposure at M12 and reduced reaction time ($\beta$ = -7.1ms [-13.8, -0.4]) (Figure 2, Supplementary Material, Table S4).

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**3.5. Sensitivity analyses**

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The results of our primary analysis persisted across the sensitivity analyses (Supplementary Material, Figure S2-4).

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**4. Discussion**

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Several phenols and parabens (bisphenol S, benzophenone-3, methyl and ethyl parabens) showed associations with eye-tracking measures. Some of these associations seem to differ

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369 between child sex; however, given our limited sample size, such results require cautious
370 interpretation. To our knowledge, this study is one of the first relying on eye-tracking
371 measures to investigate neurodevelopmental effect of synthetic phenols. Since some
372 indicators such as shorter fixation duration (associated with methylparaben, propylparaben),
373 shorter reaction times (associated with bisphenol S, ethylparaben and triclosan) and decrease
374 time looking at eyes (associated with ethylparaben) have been previously associated with
375 diagnosis of ASD (Al-Haddad et al., 2020; Joseph et al., 2009a; Sasson and Elison, 2012b;
376 Wan et al., 2019; Wass et al., 2015), we reported in the discussion section results of
377 epidemiological studies investigating effect of phenols exposure on ASD or ASD like
378 symptoms.

379

380 *Parabens*

381 We identified associations between several parabens and eye-tracking scores, including ethylparaben
382 in the main analysis and all parabens in the sex-stratified analysis. At T3 and M12, ethylparaben was
383 associated with shorter reaction times, while at M2, it was linked to less time spent looking at eyes.
384 M2 methylparaben concentration was negatively associated with the percentage of time spent looking
385 at novel faces. In the sex-stratified analysis, methylparaben at T3 was associated with reduced fixation
386 duration in boys. Although the windows of exposure differ, these findings suggest that methyl- and
387 ethylparaben may influence traits commonly observed in children with ASD (Al-Haddad et al.,
388 2020; Joseph et al., 2009a; Sasson and Elison, 2012b; Wan et al., 2019). In contrast, several
389 borderline associations were observed for propylparaben (p-values between 0.05 and 0.1), which
390 tended to indicate potentially beneficial effects on eye-tracking scores, such as longer time spent
391 looking at novel faces and eyes.

392 Few studies have investigated the associations between early paraben exposure and ASD-like
393 behaviors. In the SEPAGES cohort, no clear associations were observed between Σparabens (prenatal
394 and infancy urinary concentrations) and SRS scores(Mustieles et al., 2023). Another French study,
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restricted to boys, found that prenatal exposure to Σparabens was associated with improved prosocial behavior scores at age 3 (Philippat et al., 2017). Similarly, in a high-risk cohort, increased urinary concentration of methyl- or propyl- parabens was associated with decreased ASD risk (Sotelo-Orozco et al., 2024), aligning with our findings for propylparaben. Conversely, the only study reporting an increased ASD risk with methylparaben exposure was cross-sectional in design (Bennett et al., 2022). Overall, these studies do not support a strong association between parabens and ASD risk. However, the limited sample sizes emphasize the need for further well-designed research.

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## Bisphenols

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Bisphenol S detection at T2 was negatively associated with reaction time, a measure predictive of higher IQ scores (Thomas M. Dougherty and Haith, 1997) shown to be shorter in children with ASD (Joseph et al., 2009a). At 12 months (M12), infants with detectable bisphenol S levels showed a positive association with time spent looking at eyes. In the SEPAGES cohort, previous findings for bisphenol S were mixed: SRS scores at 2 years increased with T3 concentration (indicating worse behavior) but decreased with M2 concentration (Mustieles et al., 2023). Other studies found no association between urinary bisphenol S concentrations (pre- or postnatally) and socioemotional scores at 2 years (Liu et al., 2021) or ASD diagnosis (Sotelo-Orozco et al., 2024).

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Given the limited number of studies and the typically low detection frequency of bisphenol S (Liu et al., 2021; Mustieles et al., 2023), the current literature is insufficient to draw firm conclusions regarding the potential effects of bisphenol S on ASD-like behaviors.

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## Benzophenone-3

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In our study, postnatal - but not prenatal - benzophenone-3 concentrations were associated with improved eye-tracking scores, particularly in boys, who showed increased time spent looking at a novel face (Dzwilewski et al., 2020; Fagan and Detterman, 1992; Sterling et al., 2008). These findings
420

are partially consistent with those from a high-risk cohort, which reported decreased ASD risk with higher benzophenone-3 urinary concentrations at 3-6 months of age (Sotelo-Orozco et al., 2024).

421

422

However, a recent study using eye-tracking methods found that prenatal exposure to BP-3 was associated with slower processing speed in infants (Cragoe et al., 2024), suggesting potential adverse effects during the prenatal period. Additionally, in the SEPAGES cohort, increased BP-3 exposure at age 1 was associated with worse social behavior scores based on parent-reported SRS assessments (Mustieles et al., 2023). Together, these mixed findings may reflect differences in exposure timing, assessment methods, or population characteristics.

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## Strengths and limitations

430

Our study is among the first to use eye-tracking scores to evaluate the potential impact of environmental exposures on child neurodevelopment. These scores are less prone to measurement errors and can be applied at earlier ages compared to the questionnaires traditionally used in population-based studies to assess ASD-like symptoms (Rosenman et al., 2011). Our findings underscore their potential sensitivity to environmental influences.

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434

However, limitations include the lack of a standardized procedure for eye-tracking, which may introduce variability in parameter definitions across studies (Mastergeorge et al., 2021). This variability could affect the consistency and comparability of findings, although some indicators, such as time spent looking at eyes and novel faces, are relatively common.

435

436

437

438

Importantly, while some of the eye-tracking indicators used here (e.g., fixation duration, time spent looking at eyes, reaction time) have been studied in clinical populations — including children with ASD — they should not be interpreted as diagnostic markers. In our study, these outcomes are used as early, objective markers of attentional and social-cognitive functioning in the general population.

Comparisons with ASD literature was intended to provide functional context but does not imply clinical interpretation or elevated risk.

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444

Additionally, due to the innovative nature of these outcomes, direct comparisons with previous studies was limited, highlighting the need for further research to better understand these associations.

445

446
A key strength of our study is the exposure assessment, which utilized pooled urine samples collected repeatedly across different sensitivity windows, spanning both pregnancy and infancy. Unlike studies relying on spot samples, this approach minimizes exposure misclassification and improves the reliability of our estimates (Perrier et al., 2016). Furthermore, few studies have successfully collected biospecimens during infancy, a critical period marked by rapid brain development and heightened sensitivity to environmental exposures. Exposure levels to phenols in the SEPAGES cohort were generally lower than those reported in earlier French cohorts (EDEN, 2003–2006).

Median bisphenol A and paraben concentrations in SEPAGES infants were comparable to or lower than those reported among infants in other countries, such as the United States and Germany (Mendonca et al., 2014; Stacy et al., 2016; Völkel et al., 2011).

However, our relatively small sample size limits the power to detect associations, particularly in stratified analyses or for exposures with low detection frequencies, such as bisphenol S. This necessitates cautious interpretation of our findings.

Additionally, although we examined multiple exposure windows, our study design does not allow us to fully explore the temporal mechanisms by which exposures may influence outcomes. Approaches such as mediation analysis or life-course models could help address this in future research.

## Conclusion

Using enhanced exposure assessment and novel eye-tracking measures, we identified associations between prenatal and postnatal phenol exposure and several early markers known to be affected in individuals with neurodevelopmental disorders. Our findings add to the growing evidence of the adverse effects of phenol exposure on neurodevelopment. However, the limited sample size, combined with the scarcity of studies employing eye-tracking in environmental epidemiology, calls for cautious interpretation. Further research with larger sample sizes is needed to validate our findings.

Declaration of generative AI and AI-assisted technologies in the writing process
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During the preparation of this work the author(s) used ChatGPT in order to enhance text grammar and readability. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

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717

718

719

720 Funding

721 This project was funded by INSERM - INRAE Grant (THYREX), ANSES (HyPAxE project EST-

722 2019/1/039) and Fondation de France (ELEMENTUM - 00124527). The SEPAGES cohort was

723 supported by the **European Research Council** (N°311765-E-DOHaD), the **European Community's**

724 **Seventh Framework Programme** (FP7/2007-206 - N°308333-892 HELIX), the **European Union's**

725 **Horizon 2020** research and innovation programme (N° 874583 ATHLETE Project, N°825712

726 OBERON Project), the **French Research Agency - ANR** (PAPER project ANR-12-PDOC-0029-01,

727 SHALCOH project ANR-14-CE21-0007, ANR-15-IDEX-02 and ANR-15-IDEX5, GUMME project

728 ANR-17-CE34-0013, ETAPE project ANR-18-CE36-0005 - EDEn project ANR-19-CE36-0003-01 –

729 MEMORI project ANR 21-CE34-0022, ORANDANI project ANR-22-CE36-0018), the **French**

730 **Agency for Food, Environmental and Occupational Health & Safety - ANSES** (CNAP project

731 EST-2016-121, PENDORE project EST-2018-1-264, HyPAxE project EST-2019/1/039,

732 PENDALIRE project EST-2022-169), the **Plan Cancer** (Canc’Air project), the **French Cancer**

733 **Research Foundation Association de Recherche sur le Cancer – ARC**, the **French Endowment**

734 **Fund AGIR for chronic diseases – APMC** (projects PRENAPAR, LCI-FOT, DysCard), the **French**

735 **Endowment Fund for Respiratory Health**, the **French Fund – Fondation de France**

736 (CLIMATHES – 00081169, SEPAGES 5 – 00099903, ELEMENTUM - 00124527).

737
738 Aknowledgment

739

740 SEPAGES biospecimens are stored at Grenoble University Hospital biobank (bb-0033-00069). We

741 would like to thank the whole CRB team, led by Pr. P. Mossuz (until 2021), by Pr S. Valmary-Degano

742 (since 2021) and Mr. P. Lorimier, and in particular the technicians for the huge work of biospecimens

743 processing and pooling: Mrs. W. Jayar, Mrs. L. Than, Mrs J. Lafond, Mrs C. Chalazon, Mr T.

744 Caffaratti, Mr N. Francini and as well as Mr. G. Schummer.

745

746 We thank the Sepages study group: A. Licinia (Groupe Hospitalier Mutualiste, Grenoble), S. Bayat,

747 P. Hoffmann, E. Hullo, (Grenoble Alpes University Hospital, La Tronche), X. Morin (Clinique des

748 Cèdres, Echirolles), A. Morlot (Clinique Belledonne, Saint-Martin d'Hères), J. Lepeule, S. Lyon-

749 Caen, M. Ouidir, C. Philippat, I. Pin, J. Quentin, V. Siroux, R. Slama (Grenoble Alpes University,

750 Inserm, CNRS, IAB).

751 We thank the research team of the Grenoble Laboratoire de Psychologie et Neurocognition (LPNC),

752 for the eye tracking assessments done in its Babylab.

753 Many thanks to Dr I. Pin who was the Sepages PI from 2012 until 2022. We thank also Mr. Y. Gioria,

754 Mrs. A. Guerrache-Siebert, clinical research assistants; Mrs. M. Marceau, nurses; Mrs. E. Charvet,

755 midwives; Mrs. M. Graca, Mrs. K. Gridel, Mrs. C. Pelini, Mrs M. Barbagallo fieldworkers; Mrs.

756 A. Bossant, K. Guichardet, J-T Iltis, C. Martel, E. Quinteiro, neuropsychologists; Mrs K. Supernant,

757 A. Boudier the Sepages data managers; the staff from Grenoble Center for Clinical Investigation

758 (CIC): Prof. J.-L. Cracowski, Dr. C. Cracowski, Dr. E. Hodaj, Mrs. D. Abry, Mr. N. Gonnet and Mrs.

759 A. Tournier. A warm thank you also Dr. M. Althuser, Dr. F. Camus-Chauvet, Mr. P. Dusonchet,

760 Mrs. S. Dusonchet, Mrs. A. Royannais, Dr. D. Tournadre, Mr. P. Viossat, and clinicians from

761 Grenoble University Hospital for their support in the recruitment of the study volunteers. We also

762 thank Mrs. SF. Caraby, Mrs. J. Dujourdil, and all midwives from the four maternity wards of

763 Grenoble urban areas. SEPAGES data are stored thanks to Inserm RE-CO-NAI platform funded by

764 Commissariat Général à l'Investissement, with the implication of Sophiede Visme (Inserm DSI).

765 Many thanks to Dr. M.A. Charles, RE-CO-NAI coordinator, for her support. Finally, and importantly,

766 we would like to express our sincere thanks to participants of the Sepages study.

767

768
Figures

<figure><img src="image_3.png" /><figcaption>**Figure 1:** Participant Flow and Timing of Urinary Phenol Exposure Assessments (T2, T3, 2 and 12 Months) and Eye-Tracking Outcomes at 24 Months in the SEPAGES Cohort</figcaption></figure>
<figure><img src="image_4.png" /><figcaption>**Figure 2:** Adjusted associations between urinary concentrations of phenol metabolites and eye tracking scores for each exposure period in the SEPAGES mother-child cohort</figcaption></figure>

Abbreviations: Σ molar sum. T2, Second trimester of pregnancy; T3, Third trimester of pregnancy; M2, 2 month infancy; M12, 12 month infancy. Values are presented in Supplementary Material Table S4.. Models are adjusted for maternal age, maternal tobacco consumption, maternal cognitive function (WAIS-IV verbal component), parity, maternal professional status, breastfeeding duration, child sex, experiment time of the day.
<figure><img src="image_5.png" /><figcaption>Figure 3: Adjusted associations between urinary concentrations of phenol metabolites and eye tracking scores for each exposure period in the SEPAGES mother-child cohort according to child sex</figcaption></figure>

Abbreviations Σ molar sum. T2, Second trimester of pregnancy; T3, Third trimester of pregnancy; M2, 2 month infancy; M12, 12 month infancy. Values are presented in Supplementary Material Table S5. Models are adjusted for maternal age, maternal tobacco consumption, maternal cognitive function (WAIS-IV verbal component), parity, maternal professional status, breastfeeding duration, child sex, experiment time of the day.
Tables
<table><caption>Table 1. Description of the study population</caption><thead><tr><th>Characteristic</th><th>N</th><th>Included<br>N = 151<sup>1</sup></th><th>Not Included<br>N = 333<sup>1</sup></th><th>p-value<sup>2</sup></th></tr></thead><tbody><tr><td>Maternal tobacco consumption during pregnancy</td><td>435</td><td>17 (12%)</td><td>38 (13%)</td><td>0.7</td></tr><tr><td>Maternal age (years)</td><td>484</td><td>32.1 (30.0, 35.0)</td><td>32.2 (29.9, 35.4)</td><td>0.7</td></tr><tr><td>Child sex</td><td>479</td><td></td><td></td><td>0.4</td></tr><tr><td>Male</td><td></td><td>85 (56%)</td><td>171 (52%)</td><td></td></tr><tr><td>Female</td><td></td><td>66 (44%)</td><td>157 (48%)</td><td></td></tr><tr><td>Maternal depression during pregnancy</td><td>438</td><td></td><td></td><td>0.2</td></tr><tr><td>HAD &lt;11</td><td></td><td>103 (69%)</td><td>180 (62%)</td><td></td></tr><tr><td>HAD &gt; 11</td><td></td><td>46 (31%)</td><td>109 (38%)</td><td></td></tr><tr><td>Maternal education</td><td>484</td><td></td><td></td><td>0.2</td></tr><tr><td>Highschool + 2 years or less</td><td></td><td>21 (14%)</td><td>62 (19%)</td><td></td></tr><tr><td>Highschool + 3 years or more</td><td></td><td>130 (86%)</td><td>271 (81%)</td><td></td></tr><tr><td>Parity</td><td>484</td><td></td><td></td><td>0.2</td></tr><tr><td>First child</td><td></td><td>76 (50%)</td><td>146 (44%)</td><td></td></tr><tr><td>Second child</td><td></td><td>65 (43%)</td><td>149 (45%)</td><td></td></tr><tr><td>Third child or more</td><td></td><td>10 (6.6%)</td><td>38 (11%)</td><td></td></tr><tr><td>Professional status at inclusion</td><td>444</td><td></td><td></td><td>&gt;0.9</td></tr><tr><td>Working</td><td></td><td>127 (87%)</td><td>257 (86%)</td><td></td></tr><tr><td>Not working, not looking for work</td><td></td><td>13 (8.9%)</td><td>26 (8.7%)</td><td></td></tr><tr><td>Not working, looking for work</td><td></td><td>6 (4.1%)</td><td>15 (5.0%)</td><td></td></tr><tr><td>Breastfeeding duration (weeks)</td><td>445</td><td>31 (17, 48)</td><td>30 (17, 47)</td><td>0.4</td></tr><tr><td>Maternal WAIS- verbal score</td><td>322</td><td>12.00 (10.00, 14.00)</td><td>12.00 (10.00, 15.00)</td><td>0.5</td></tr><tr><td>Ethnicity</td><td>484</td><td></td><td></td><td>&lt;0.001</td></tr><tr><td>European</td><td></td><td>139 (92%)</td><td>262 (79%)</td><td></td></tr><tr><td>Missing</td><td></td><td>9 (6.0%)</td><td>64 (19%)</td><td></td></tr><tr><td>Other<sup>a</sup></td><td></td><td>3 (2.0%)</td><td>7 (2.1%)</td><td></td></tr><tr><td>Gestation age at T2 sample (weeks)</td><td>477</td><td>18.00 (16.57, 18.86)</td><td>17.57 (16.29, 18.86)</td><td>0.13</td></tr><tr><td>Gestation age at T3 sample (weeks)</td><td>456</td><td>34.21 (32.14, 35.29)</td><td>34.00 (32.14, 35.14)</td><td>0.8</td></tr><tr><td>Age at M2 sample (months)</td><td>427</td><td>1.55 (1.42, 1.78)</td><td>1.68 (1.48, 2.44)</td><td>&lt;0.001</td></tr><tr><td>Age at M12 sample (months)</td><td>386</td><td>12.13 (11.87, 12.56)</td><td>12.26 (11.93, 12.73)</td><td>0.009</td></tr><tr><td>N samples in M12 pool</td><td>387</td><td>7.00 (6.00, 7.00)</td><td>6.00 (5.00, 7.00)</td><td>0.016</td></tr><tr><td>N samples in M2 pool</td><td>427</td><td>7.00 (6.00, 7.00)</td><td>7.00 (6.00, 7.00)</td><td>0.5</td></tr><tr><td>N samples in T2 pool</td><td>477</td><td>21.00 (20.00, 21.00)</td><td>21.00 (20.00, 21.00)</td><td>0.13</td></tr><tr><td>N samples in T3 pool</td><td>455</td><td>21.00 (20.00, 21.00)</td><td>21.00 (20.00, 21.00)</td><td>0.009</td></tr><tr><td>Sample specific gravity in T2 pool</td><td>477</td><td>1.018 (1.014, 1.020)</td><td>1.018 (1.015, 1.021)</td><td>0.5</td></tr><tr><td>Sample specific gravity in T3 pool</td><td>456</td><td>1.017 (1.013, 1.020)</td><td>1.017 (1.014, 1.020)</td><td>0.2</td></tr><tr><td>Sample specific gravity in M2 pool</td><td>427</td><td>1.0040 (1.0040, 1.0050)</td><td>1.004 (1.004, 1.005)</td><td>0.8</td></tr><tr><td>Sample specific gravity in M12 pool</td><td>387</td><td>1.011 (1.009, 1.014)</td><td>1.011 (1.009, 1.015)</td><td>0.3</td></tr><tr><td>Reaction time (ms)</td><td>145</td><td>282 (252, 316)</td><td></td><td></td></tr><tr><td>Fixation duration (ms)</td><td>150</td><td>5.86 (5.78, 5.97)</td><td></td><td></td></tr><tr><td>Time spent looking at novel face (%)</td><td>150</td><td>0.55 (0.50, 0.60)</td><td></td><td></td></tr><tr><td>Time spent looking at eyes (%)</td><td>150</td><td>0.73 (0.58, 0.81)</td><td></td><td></td></tr><tr><td>Age at eye tracking experiment in months</td><td>151</td><td>24.87 (24.51, 25.33)</td><td></td><td></td></tr><tr><td>Eye tracking experiment hour</td><td>151</td><td></td><td></td><td></td></tr><tr><td>8AM - 12PM</td><td></td><td>122 (81%)</td><td></td><td></td></tr><tr><td>12PM - 14PM</td><td></td><td>7 (4.6%)</td><td></td><td></td></tr><tr><td>14PM - 16PM</td><td></td><td>22 (15%)</td><td></td><td></td></tr></tbody></table>

Abbreviations: HAD, Hospital Anxiety and Depression scale score. a Includes Africa, America, Oriental Mediterranean countries, South East Asia and Other.

<footnote n="1">¹n (%); Median (Q1, Q3)</footnote>

<footnote n="2">² Pearson's Chi-squared test; Wilcoxon rank sum test; Fisher's exact test</footnote>
<table><caption>Table 2: Detection rates of phenols urinary concentrations by sampling period</caption><thead><tr><th rowspan="2">Compound</th><th rowspan="2">LOD</th><th rowspan="2">LOQ</th><th rowspan="2">%>LOD</th><th colspan="3">2nd trimester (N = 151)</th><th colspan="3">3rd trimester (N = 150)</th><th colspan="3">2 months (N = 144)</th><th colspan="3">12 months (N = 145)</th></tr><tr><th>p5</th><th>p50</th><th>p95</th><th>%>LOD</th><th>p5</th><th>p50</th><th>p95</th><th>%>LOD</th><th>p5</th><th>p50</th><th>p95</th><th>%>LOD</th><th>p5</th><th>p50</th><th>p95</th></tr></thead><tbody><tr><td>Bisphenol A</td><td>0.04</td><td>0.1</td><td>99%</td><td>0.64</td><td>1.72</td><td>7.80</td><td>98%</td><td>0.43</td><td>1.45</td><td>9.53</td><td>100%</td><td>0.21</td><td>0.74</td><td>3.03</td><td>100%</td><td>0.88</td><td>2.74</td><td>14.02</td></tr><tr><td>Bisphenol A (conj.)</td><td>0.04</td><td>0.1</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>0.05</td><td>0.48</td><td>2.60</td><td>-</td><td>0.47</td><td>2.13</td><td>11.33</td></tr><tr><td>Bisphenol S</td><td>0.1</td><td>0.4</td><td>28%</td><td>-</td><td>-</td><td>1.00</td><td>30%</td><td>-</td><td>-</td><td>1.00</td><td>46%</td><td>-</td><td>-</td><td>1.00</td><td>70%</td><td>-</td><td>1.00</td><td>1.0</td></tr><tr><td>Ethylparaben</td><td>0.04</td><td>0.1</td><td>99%</td><td>0.25</td><td>0.84</td><td>43.01</td><td>99%</td><td>0.24</td><td>0.76</td><td>26.96</td><td>88%</td><td>0.03</td><td>0.10</td><td>21.03</td><td>99%</td><td>0.21</td><td>4.34</td><td>397.20</td></tr><tr><td>Propylparaben</td><td>0.04</td><td>0.1</td><td>78%</td><td>0.00</td><td>0.32</td><td>20.08</td><td>73%</td><td>0.00</td><td>0.26</td><td>91.08</td><td>60%</td><td>0.00</td><td>0.07</td><td>92.59</td><td>92%</td><td>0.03</td><td>2.93</td><td>431.81</td></tr><tr><td>Methylparaben</td><td>0.04</td><td>0.1</td><td>100%</td><td>2.29</td><td>11.33</td><td>180.83</td><td>100%</td><td>2.03</td><td>9.56</td><td>1,452.64</td><td>100%</td><td>0.17</td><td>0.85</td><td>1,224.60</td><td>100%</td><td>1.78</td><td>86.04</td><td>2,395.23</td></tr><tr><td>Methylparaben (conj.)</td><td>0.04</td><td>0.1</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>0.13</td><td>0.64</td><td>808.20</td><td>-</td><td>1.22</td><td>81.29</td><td>2,383.80</td></tr><tr><td>ΣParabens</td><td>-</td><td>-</td><td>-</td><td>0.02</td><td>0.10</td><td>1.78</td><td>-</td><td>0.02</td><td>0.08</td><td>9.97</td><td>-</td><td>0.00</td><td>0.01</td><td>8.73</td><td>-</td><td>0.02</td><td>0.74</td><td>21.49</td></tr><tr><td>ΣParabens (conj.)<sup>a</sup></td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>0.00</td><td>0.01</td><td>5.99</td><td>-</td><td>0.01</td><td>0.67</td><td>21.24</td></tr><tr><td>Benzophenone-3</td><td>0.04</td><td>0.1</td><td>100%</td><td>0.18</td><td>0.90</td><td>33.50</td><td>100%</td><td>0.14</td><td>0.77</td><td>20.20</td><td>97%</td><td>0.04</td><td>0.34</td><td>4.84</td><td>99%</td><td>0.13</td><td>0.39</td><td>1.56</td></tr><tr><td>Triclosan</td><td>0.04</td><td>0.1</td><td>99%</td><td>0.21</td><td>0.93</td><td>153.64</td><td>97%</td><td>0.13</td><td>0.86</td><td>125.94</td><td>92%</td><td>0.02</td><td>0.30</td><td>1.59</td><td>93%</td><td>0.03</td><td>0.25</td><td>1.64</td></tr></tbody></table>

Abbreviations: LOD: Limit of detection, LOQ: Limit of quantification, Σ: molar sum

For bisphenol A and methylparaben, both total and conjugated concentrations are presented for infancy samples, due to suspected contamination of free forms from diaper materials. For other compounds, only total concentrations (free + conjugated) are reported.

<footnote>aΣParabens (conj.) corresponds to the sum of methylparaben (conjugated), ethylparaben (total), and propylparaben (total).</footnote>