Endocrine and Reproductive Health Considerations of Sunscreen UV Filters: Insights from a Comprehensive Review 2014–2024

Abstract

Purpose of Review

Chemical (organic) ultraviolet (UV) filters—carbon-based compounds widely used in sunscreen formulations—are essential for protecting against harmful UV radiation. However, emerging evidence over the last decade (2014–2024) has raised concerns regarding their potential endocrine-disrupting effects, environmental persistence, and bioaccumulation. This comprehensive review evaluates the endocrine, reproductive, and developmental health impacts of organic UV filters, with a focus on benzophenone derivatives such as BP-3, BP-2, and 4-OHBP.

Recent Findings

The analysis incorporates data from 75 studies identified through PRISMA-guided screening of epidemiological and human research. Findings reveal significant hormonal disruptions, including reduced testosterone levels in adolescent males, altered thyroid hormones in pregnant women, and associations with delayed pubertal development in boys and early menarche in girls. Mixed exposures to multiple UV filters, frequently occurring in real-world scenarios, demonstrate cumulative and complex effects, particularly on thyroid hormone levels and reproductive health. In men, benzophenones are associated with decreased sperm quality and motility, while in women, their impact on ovarian reserve and fertility outcomes appears less pronounced. Prenatal exposure studies show mixed outcomes, ranging from reduced neonatal size and gestational age to increased placental-to-birth weight ratios.

Summary

This review underscores the dual nature of organic UV filters, emphasizing their importance in photoprotection while highlighting the need for a balanced approach to safety evaluations. Future research should prioritize long-term cohort studies, assessments of mixed exposure effects, and the development of safer alternatives. Addressing these challenges is crucial for mitigating risks to human health and the environment while maintaining the protective benefits of sunscreens.

Introduction

Global Statistics on Sunscreen Usage Growth

Ultraviolet (UV) solar radiation that passes through the surface of the earth’s atmosphere is an important health risk factor. Solar UV radiation that adds to ambient sunlight consists of 90 to 95% UVA (wavelengths 320–400 nm) and 5 to 10% UVB radiation (280–320 nm). UVC (280–100 nm) does not pass through atmospheric ozone. Although the skin serves as the body’s primary barrier against ultraviolet (UV) radiation, its natural photoprotective mechanisms—such as melanin production and DNA repair—are often insufficient to fully prevent UV-induced damage. As a result, external photoprotective measures, particularly sunscreens containing active UV-filtering compounds, are essential to prevent adverse effects such as sunburn, photoaging, melanoma, other skin cancers, and photoimmunosuppression [1, 2]. The consciousness about the importance of sun protection has increased over the last few years. Dermatological associations recommend applying sunscreens with a broad-spectrum filter, with a sun protection factor (SPF) of 30 or higher daily [3, 4]. It is recommended to apply 2 mg of sunscreen per square centimetre of skin [5], which is a significant amount of skincare product. Thus, the global sunscreen market is growing, generating revenues projected to experience an annual growth rate from USD 11.6 billion in 2018 to USD 24.4 billion by 2029 [6]. Besides intentional use, unintentional exposure to UV filters can also happen through the application of personal care products, where these filters are included as ingredients preventing UV degradation of the product itself [7].

Classification of UV-Protective Filters

In 1974 the conception of SPF was developed to standardise the measurement of sunscreen efficacy. This term was defined as “the ratio of the smallest dose of UVB radiation required to produce minimal erythema on sunscreen-protected skin compared to the necessary dose of UVB to produce the same amount of erythema on non-protected skin” [8]. There is a wide diversity of products available on the market that have photoprotective properties. These UV filters are divided into two main groups: inorganic (physical, mineral) and organic (chemical) (Fig. 1). The organic UV filters are categorised based on shared chemical structures, with the most significant classes being: benzophenones, salicylic acid derivatives, aminobenzoic acid derivatives, dibenzoylmethane derivatives, benzylidenecamphor derivatives, cinnamic acid derivatives, triazines, benzimidazole derivatives, and benzotriazole derivatives [9].

Fig. 1.

Classification of active ingredients in sunscreens and their regulatory status across major markets [10–13]

Inorganic filters approved by the Food and Drug Administration (FDA) include zinc oxide (ZnO) and titanium dioxide (TiO₂). These filters partially absorb, reflect and scatter UVA and UVB radiation thus ensuring broad-spectrum protection [14]. Due to the large particle size and high refractive indices of both metal oxides, they create an opaque film on the skin after sunscreen application. Nanotechnology allowed the application of nano-sized particles into the sunscreen formulas resulting in enhanced consumer acceptability [9, 14].

Organic filters include a wider range of substances with photoprotective abilities. They absorb specific UV radiation and convert them into non-damaging wavelengths of light or heat. Therefore, many different types of organic filters are likely used in commercially available sunscreen products to provide broad-spectrum UV protection. The most commonly used substances in cosmetics include: benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), benzophenone-4 (BP-4), 4-methyl benzylidene camphor (4-MBC), 3-benzylidene camphor (3-BC), octyl methoxycinnamate (OMC), IMC (isopentyl-4-methoxycinnamate), octocrylene (OC) [15].

In the European Union 30 UV filters permitted to be added in cosmetics are listed in Annex VI to the EU Cosmetics Regulation (EUR-LEX 1223/2009) and they are considered as cosmetics [10]. Australia regulates 29 approved agents of sunscreens as therapeutic goods by the Therapeutic Goods Administration (TGA) under the Therapeutic Goods Act 1989 [11]. The US FDA classifies sunscreens as over-the-counter (OTC) drugs [12]. Furthermore, the FDA divides 16 approved UV filters into three categories of substances generally recognized as safe and effective (GRASE) [13]. TiO₂ and ZnO are classified as category I, 4-aminobenzoic acid (PABA) and trolamine salicylate are in category II classified as not GRASE. Category III includes cinoxate, dioxybenzone (benzophenone-8), ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, and sulisobenzone (BP-4) for which the record contains significant data gaps or fewer data gaps comprising oxybenzone (BP-3) and avobenzone. For ingredients proposed as category III further research is required to determine GRASE status and, in the meantime, FDA does not classify them as unsafe [13].

Environmental Concern

Besides benefits carried with regular usage of skin care products containing UV-protective filters, there also comes an environmental and human health concern. This phenomenon can be explained by the hydrophobic/lipophilic structure of most UV filters.

Ingredients with photoprotective abilities have found application in many different branches of industry (e.g. plastic additives, clothing production, food packaging) leading to occurrence in several environmental areas. Their presence has been detected in ambient water, sediment, soil, and indoor dust, potentially subjecting the residing organisms to harmful or disruptive effects [16]. UV filters enter the aquatic environment through direct (i.e. wash-off from the skin while being in water) or indirect input (i.e. wastewater discharges) and were detected in rivers, lakes, seawater, wastewater and sludge. Additionally, regarding coral reefs, studies had shown that UV filters even at low concentrations cause coral bleaching, i.e., the loss of symbiotic zooxanthellae hosted within scleractinian corals, by promoting viral infections [17].

However, available data mainly concerns organic filters. Metal oxides used in sunscreens can be spread to the environment from several different sources, thus detailed data is difficult to obtain. Beyond their ecological effects, organic UV filters have also raised recent increasing concern due to their potential impact on human health, particularly through endocrine and reproductive pathways [18].

The Aim of the Study

Recent studies also report health concerns regarding the use of organic UV filters, encompassing allergic reactions as well as endocrine and reproductive disorders, hence being classified as Endocrine Active Chemicals (EACs) [18]. The US FDA conducted two randomized clinical trials on healthy patients and confirmed that all sunscreen active ingredients investigated during the study (avobenzone, benzophenone-3, octocrylene and ecamsule) were identified in blood plasma [19]. Furthermore, presence of various UV filters was discovered in urine, seminal fluid, breast milk, amniotic fluid and cord blood cells [20–23]. Since sunscreens are applied to the skin, dermal exposure is the primary route of contact. Other human exposure pathways are ingestion (i.e. hand-to-mouth habit, sunscreen lipsticks) and inhalation (particularly through the use of aerosolized sunscreen sprays, powders, or mist formulations that generate airborne particles) [16]. Although, the level of systemic absorption depends on factors such as the body site of application, the person’s age, the health status of the skin, the frequency of the application, the duration of skin contact with the product and the possible presence of chemicals that enhance the penetration of other substances [24].

Based on the increasing variety of sunscreen products and regulatory pressure to confirm the safety of these formulations containing UV filters, up-to-date data on endocrine-disrupting properties has been necessary. The current study was designed to organise knowledge in a priori objectives: a) to summarise, compare and meta-analyse available studies from last 10 years (2014–2024) regarding internal exposure of organic UV filters and health outcomes. b) to evaluate possible mechanisms of action from in vitro and in vivo data c) to identify gaps in the existing knowledge pointing the way for further research.

Methodology

Search Strategy and Inclusion Criteria—PRISMA

A comprehensive literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The literature search aimed to identify all epidemiological, human studies published between 2014 and 2024, addressing the endocrine and reproductive health effects of organic UV filters used in sunscreens. The databases searched included PubMed, Scopus, Web of Science, and Embase. We considered cross-sectional, longitudinal and prospective study designs. The literature search was conducted in duplicate by two researchers. In the first step, two independent researchers identified available evidence of endocrine disrupting properties of UV filters present in sunscreens. Key search terms included combinations of:"organic UV filters","endocrine activity","reproductive health","benzophenones","octinoxate","homosalate","endocrine-disrupting chemicals (EDCs)","hormonal effects"and"sunscreen exposure". Boolean operators ("AND,""OR") were used to refine the search. The search strategy was customized for each database to ensure comprehensive coverage of relevant studies and was conducted in titles, abstracts, and full articles.

Inclusion and Exclusion Criteria

Studies were included if they: i) evaluated the effects of organic UV filters on endocrine or reproductive health in humans; ii) evaluated sunscreen exposure quantitatively—either through internal dose biomarkers (e.g., urinary or blood concentrations) or well-defined product usage metrics (e.g., frequency of sunscreen application)—and reported associations with health outcomes using effect estimates or comparable statistical measures; iii) were published in English between January 1, 2014, and January 1, 2024; iv) included controlled experimental, cohort, case–control, or cross-sectional study designs.

Exclusion criteria: i) non-peer-reviewed studies, reviews, editorials, or opinion articles; ii) studies using animal models, mathematical models, cell cultures, and invertebrates; iii) insufficient data on exposure or health outcomes; iv) outcomes were assessed in a population of > 10 people (case studies); v) studies with English abstracts but a full text in a language other than English were also excluded. Figure 2 shows the PRISMA flow diagram of the literature review pipeline. The results were organized according to the chemical groups of UV filters followed by sample size.

Fig. 2.

Prisma flowchart results

Data Extraction and Quality Assessment

Overall 1474 studies were retrieved, 641 screened, and 78 included in the final analyses (Fig. 2). Quality assessment of each included study was conducted using validated tools appropriate for non-randomized epidemiological research. For observational studies, we applied the ROBINS-I tool and, in some cases, the Newcastle–Ottawa Scale (NOS) to evaluate domains such as selection bias, measurement of exposure and outcomes, and adjustment for confounding. The PRISMA 2020 checklist was used to structure and report the overall review process, in accordance with best practices for systematic reviews (Page et al., 2021).

UV Filters Expossure and Various Health Effects

Benzophenone Derivatives Classification

The typical structure of benzophenone derivatives consists of two benzene rings linked by a carbonyl group. Additionally, featured by an ortho substitution with a hydrogen-donor group and a para substitution with an electron-donating group [9].

Benzophenone-3

2-hydroxy-4-methoxybenzophenone known as oxybenzone or BP-3 was found naturally in flowering plants. Next to BP-4 it is the most commonly used BP-type UV filter [25], approved in the US, EU and Australia. BP-3 is a broad-spectrum filter with highly lipophilic and accumulative properties [9]. In humans, BP-3 can be absorbed through the skin at a rate of up to 2% after topical application and is efficiently absorbed when ingested. In the EU and US the concentration of BP-3 can reach a maximum of 6% in cosmetics products [26, 27] and in Australia it is a concentration of 10% [11]. BP-1 (2,4-diOH-BP), BP-8 (2,2′-diOH-4-methoxy-BP) and 4-OH-BP are the metabolites of BP-3 that occur frequently among analytes investigated in articles in Table 1. [16, 25, 28]. The vast majority of articles found focused on studying the effects of exposure to UV filters from the benzophenone class. Therefore, the articles listed in Table 1 pertain to this group of compounds [16, 25, 28].

Table 1.

Exposure to different benzophenone derivatives and health outcomes reported in included studies

No	No. of participants	Population	Country	Analytes	Matrix (research material)	Research endpoints	Main conclusion	Ref
1	473	Mother-son pairs	France	BP-3	Urine	Placental weight at birth, placental–to–birth weight ratio (PFR)	A log-unit increase in urinary BP-1 concentration was associated with an 18.4 g decrease in fetal weight (95% CI: − 33.6, − 3.3; p = 0.017) and a 4.7 g decrease in placental weight (95% CI: − 8.4, − 1.1; p = 0.011). Associations for BP-3 were not statistically significant	[29]
2	588	Male and female children (aged 6–11) and adolescents (aged 12–)	USA	BP-3	Urine	Serum total TT levels	Inverse association between BP-3 exposure and significantly lower TT in adolescent boys only. No significant associations were observed in children (male or female). Among adolescent males (ages 12–19), each log-unit increase in urinary BP-3 concentration was associated with a 5.6% decrease in total serum testosterone (β =  − 0.058; 95% CI: − 0.106, − 0.011; p < 0.05). No significant associations were found in females or younger boys	[30]
3	233	School-age children	China	BP-3, BP-2	Urine	Children’s pubertal development in a gender-specific manner	Association between BP-3 exposure and delayed genital and pubic hair development in boys Association between BP-2 exposure and earlier pubertal development in girls. In young men, a log10-unit increase in urinary BP-1 concentration was associated with a − 6.58% change in progressive sperm motility (95% CI: − 11.23%, − 1.94%). Similar inverse associations were found for 4OH-BP (− 5.96%; 95% CI: − 10.54%, − 1.14%). No significant associations were observed with sperm concentration or morphology	[31]
4	195	65 men genotyped for FLG R501X, 2282del4, and R2447X loss-of-function mutations, 130 non-carriers (controls)	Denmark	BP, BP-1, BP-2, BP-3, 4-OHBP, 4-MBP	Urine, blood, semen	Semen quality and reproductive hormones (FSH, LH, SHBG, TT, inhibin B, and estradiol)	In the group of FLG mutation carriers, urinary levels of BP-1, BP-3 and 4-OHBP were associated with higher serum TT and estradiol levels and lower FSH. Tendency towards a lower percentage of progressive motile spermatozoa was detected. BP-3: + 4.8% testosterone per log-unit increase (95% CI: + 1.2%, + 8.6%); 4-OHBP: + 5.4% estradiol per log-unit (95% CI: + 1.3%, + 9.7%); BP-1: − 3.9% FSH per log-unit (95% CI: − 6.8%, − 0.9%)	[32]
5	NAD	Men	Denmark	BP-3, BP-4, BP-5, BP-8	Semen	Acrosome reaction, penetration, hyperactivation, and viability in human sperm cells	No significant associations	[33]
6	22	Women with premenopausal status, (aged 20–54)	Spain	BP-1, BP-3, 4-OHBP	Endometriotic tissue, urine	Development and progression of endometriosis	Positive association with the expression of key genes for the development and proliferation of endometriosis. Higher urinary concentrations of methylparaben (MeP) were significantly associated with increased expression of genes related to cell adhesion (e.g., ITGB2, β = 1.13, p = 0.006), inflammation (e.g., IL6ST, β = 1.26, p = 0.007), and hormone response (e.g., ERα, β = 0.78, p = 0.003). Conversely, MeP was significantly associated with decreased expression of the proliferation-inhibitory gene DUSP6 (β = –0.90, p = 0.005)	[34]
7	600	Pregnant women	China	BP-1, BP-2, BP-3, BP-8, and 4-OH-BP	Serum	Fetal growth (weight, birth chest circumference (BC), head circumference (HC), and birth length (BL), thyroid hormone levels, glucose levels	Inverse association between BP-3 exposure and reduced neonatal birth weight and birth chest circumference during the third trimester. Co-exposure to BP-3 was linked to decreased levels of thyroid stimulating hormone (TSH), glucose and increased serum creatinine levels (Cr). A one-quantile increase in exposure to benzophenone-type UV filters during the third trimester was significantly associated with reductions in neonatal birth weight (β =  − 38.97 g, p = 0.039) and birth chest circumference (β =  − 0.160 cm, p = 0.037), with BP-2 being the largest contributor (39% and 36%, respectively)	[35]
8	220	Couples interested in becoming pregnant	USA	BP-1, BP-2, BP-3, BP-8, 4-OHBP	Urine	Secondary sex ratio (ratio of males to females at birth)	Higher maternal urinary concentrations of 4-hydroxybenzophenone (4-OH-BP) were significantly associated with an increased likelihood of male births, with a relative risk (RR) of 1.87 (95% CI: 1.27–2.74) for the second tertile and 1.80 (95% CI: 1.13–2.87) for the third tertile compared to the first (p-trend = 0.02). In contrast, both maternal and paternal urinary concentrations of BP-2 were significantly associated with an increased likelihood of female births, with maternal BP-2 showing an RR of 0.62 (95% CI: 0.43–0.91) for the second tertile and paternal BP-2 showing an RR of 0.67 (95% CI: 0.45–0.99) for the third tertile (p-trend = 0.04)	[36]
9	123	40 women with polycystic ovary syndrome PCOS (aged 20–41), and 83 healthy women (controls)	China	BP-3	Urine	Development and progression of PCOS	No significant association overall between urinary concentrations of personal care product chemicals (BPA, TCS, BP-3, HMS, and OC) and polycystic ovary syndrome (PCOS) (p > 0.05). However, in women with BMI ≥ 24, octocrylene (OC) was significantly associated with PCOS with an adjusted odds ratio of 1.512 (95% CI: 1.043–2.191, p = 0.029)	[37]
10	215	Men (aged 18–23)	Spain	BP-1, BP-2, BP-3, BP-8, 4-OHBP	Urine, serum, semen	Reproductive health	Urinary concentrations of BP-1 and BP-3 were significantly positively associated with serum FSH levels (BP-1: β = 0.08, 95% CI: 0.009–0.15; BP-3: β = 0.04, 95% CI: 0.0002–0.08). BP-1 was also associated with higher T/E2 ratio (β = 0.04, 95% CI: 0.002–0.07) and lower inhibin B/FSH ratio (β =  − 0.11, 95% CI: − 0.21 to − 0.006). No significant associations were found between urinary BP-type UV filters and any semen parameters	[38]
11	300	Men	Denmark	BP, BP-1, BP-3, 4-MBP	Urine, serum, semen	Reproductive health	Benzophenone-1 (BP-1) and benzophenone-3 (BP-3) were detected in 19% and 27% of seminal fluid samples, respectively, and their concentrations in urine and seminal fluid were significantly correlated (BP-1: p < 0.001, 3rd-degree polynomial; BP-3: p < 0.001, 2nd-degree polynomial), indicating direct exposure of sperm to UV filters at biologically relevant levels	[21]
12	521	High school-age boys and girls	China	BP-2, BP-3, EHMC, PABA	Urine	Pubertal development	In boys, each log-unit increase in urinary EHMC was significantly associated with delayed pubertal development: testicular volume (OR = 0.644; 95% CI: 0.460–0.902; P = 0.01) and genital development (OR = 0.714; 95% CI: 0.516–0.988; P = 0.042). BP-3 also showed delay in testicular volume (OR = 0.588; 95% CI: 0.351–0.986; P = 0.044) In girls, urinary OD-PABA was significantly associated with earlier and faster breast and pubic hair development: breast onset (OR = 3.345; 95% CI: 1.029–10.874; P = 0.045), pace of breast development (OR = 1.425; 95% CI: 1.014–2.002; P = 0.041), and pubic hair (OR = 1.755; 95% CI: 1.134–2.715; P = 0.012)	[39]
13	847	Mother-infant pairs (pregnant women aged 20–44)	China	BP-1, BP-3, 4-OHBP	Urine	Fetal birth length	Each log unit increase in maternal urinary BP-1 and 4-OH-BP in the 1 st trimester was significantly associated with decreased birth length by 0.06 cm (95% CI: –0.11, –0.01) and 0.08 cm (95% CI: –0.15, –0.01), respectively. In girls, BP-1 and BP-3 in the 3rd trimester were associated with reduced birth weight (–27.99 g and –19.75 g) and length (–0.08 cm each), with p-values < 0.05	[40]
14	327	Children (aged 7–15)	China	BP-2, BP-3	Urine	Adiposity measures in peripubertal children	Exposure to organic UV filter mixtures was significantly associated with reduced adiposity in peripubertal boys, with effects including a − 1.399 kg/m2 reduction in BMI (95% CI: − 2.246 to − 0.551) and 55% lower odds of overweight/obesity (OR = 0.453, 95% CI: 0.326 to 0.630) comparing 75th vs. 25th percentile exposure levels	[41]
15	922	Pregnant women	Puerto Rico	BP-3	Urine, blood	Gestational age	Prenatal exposure to benzophenone-3, methyl-paraben, and propyl-paraben was significantly associated with increased gestational age by 1.90 (95% CI: 0.54, 3.26), 1.63 (95% CI: 0.37, 2.89), and 2.06 days (95% CI: 0.63, 3.48), respectively. Triclocarban was associated with a suggestive decrease in gestational age (− 1.96 days; 95% CI: − 4.11, 0.19)	[42]
16	101	54 patients with type 2 diabetes (aged 28–68), and 47 healthy patients (controls)	Saudi Arabia	BP-1, BP-2, BP-3, 4-OHBP	Urine	Type 2 diabetes	Individuals in the highest quartile of urinary bisphenol F (BPF) had an adjusted odds ratio (OR) of 174 (95% CI: 12.9–2,400; p < 0.01) for type 2 diabetes compared to those in the lowest quartile. Similarly, ethyl paraben (EtP) showed a strong association with an adjusted OR of 104 (95% CI: 10.6–1,000; p < 0.01) in the top quartile	[43]
17	157 (urine samples), 155 (serum samples)	Mother–child pairs	Denmark	BP-1, BP-3, 4-OHBP	Urine, serum	Maternal thyroid hormone and growth factor levels, birth outcomes (gestational age, weight, length, head circumference)	Benzophenone-3 (BP-3) was detectable in 92% of maternal urine samples and in 18% of cord blood samples, with a significant correlation between maternal urine and amniotic fluid levels (Spearman’s ρ = 0.604, p = 0.022), and between maternal serum and amniotic fluid levels (ρ = 0.571, p = 0.026). Concentrations of BP-1 and BP-3 in fetal and cord blood were ~ 10 × lower than in maternal serum and ~ 1000 × lower than in maternal urine, indicating limited but significant placental transfer at high maternal exposure levels	[44]
18	142	Women who underwent infertility treatments (aged 18–45)	USA	BP-3	Urine, serum	Reproductive health	In this study, urinary benzophenone-3 was not associated with ovarian reserve overall, but stratified models showed significant effects: among women aged ≤ 35 years, a 1-unit increase in log benzophenone-3 was associated with a 9% lower antral follicle count (AFC; 0.91, 95% CI: 0.86–0.97), and among women > 35 years, it was associated with a 0.73 IU/L higher day 3 FSH (95% CI: 0.12–1.34)	[45]
19	504	Children (aged 6–9)	China	BP-3, EHMC, OC	Urine	Childhood obesity	The study found that urinary EHMC levels were significantly positively associated with childhood obesity in girls [Adjusted OR = 2.642, 95% CI: 1.019–6.853, p = 0.046], while OC levels were inversely associated [Adjusted OR = 0.022, 95% CI: 0.001–0.817, p = 0.038]	[46]
20	441	Women (aged 20–45)	South Korea	BP-1, MBP	Urine, blood	Kidney function	Monobutyl phthalate (MBP) and benzophenone-1 (BP-1) were significantly and positively associated with urinary albumin-to-creatinine ratio (ACR), a kidney function marker, in healthy women. In the multi-pollutant model, MBP had a β = 0.15 (95% CI: 0.06, 0.23; p < 0.001) and BP-1 had a β = 0.11 (95% CI: 0.07, 0.16; p < 0.001), indicating robust associations	[47]
21	158	Men (aged 18–23)	Spain	BP-1, BP-2, BP-3, BP-8, 4-OHBP	Urine, semen	Reproductive health, semen quality	The main result of the study is that an increase in urinary 4OHBP concentration was significantly associated with a decrease in sperm DNA fragmentation (SDF) index: − 5.5% (95% CI: − 10.7, − 0.3) at the 50th percentile and − 5.4% (95% CI: − 10.8, − 0.1) at the 75th percentile	[48]
22	439	Pregnant women (aged ≥ 18 years old)	USA	BP-3	Urine, blood	Thyroid hormones	An interquartile range (IQR) increase in butyl paraben was associated with a statistically significant 2.76% decrease in maternal total triiodothyronine (T3) (95% CI: − 5.25, − 0.26), and triclocarban levels above the limit of detection were associated with a 5.71% decrease in T3 (95% CI: − 10.45, − 0.97)	[49]
23	450	Women undergoing in vitro treatment	Poland	BP-3	Urine	Reproductive health	Higher urinary butyl paraben (BP) concentrations were significantly associated with a reduction in MII oocyte count, both as a continuous variable (β = –0.20; p = 0.007) and when comparing highest vs. lowest exposure quartiles (β = –0.21; p = 0.02). No significant associations were found with other reproductive outcomes or chemicals	[50]
24	111 women (follicular fluid), 3 (semen donors)	Women undergoing fertility treatment; 3 young male donors	Denmark	BP-3	Follicular fluid, semen	Reproductive health, hormone levels	Women in the highest tertile of dibutyl phthalate metabolites had significantly lower antral follicle count (MiBP: β = –5.35 [95% CI: –9.06, –2.00], MnBP: β = –5.25 [95% CI: –9.00, –2.00]) and lower odds of detecting a heartbeat at gestational week 7 (MiBP: OR = 0.35 [95% CI: 0.14, 0.91], p = 0.02)	[51]
25	442	Mother–child pairs	France	BP-3	Urine (mothers), blood spots (newborns)	Neonatal thyroid hormones levels	In girls, prenatal exposure to triclosan, three parabens, and OH-MPHP was significantly associated with lower T4 levels (e.g., triclosan β =  − 1.18 ng/mL; 95% CI: − 2.32, − 0.04). No consistent associations were found with TSH	[52]
26	404	Women and their children (aged 4–9)	USA	BP-3	Urine (mothers)	Childhood fat mass after prenatal exposure	After adjustment, maternal urinary benzophenone-3 concentration in the third trimester was associated with lower percent fat mass in girls (β =  − 1.51, 95% CI =  − 3.06 to 0.01), but not in boys (β =  − 0.20, 95% CI =  − 1.69 to 1.26)	[53]
27	789	Women (aged 18–45)	USA	BP-3	Urine	Reproductive health, self-reported infertility	Exposure to a combination of benzophenone-3, bisphenol-A, and triclosan (Cluster 2) was significantly associated with higher self-reported female infertility (PR = 1.13, 95% CI: 1.04–1.24, p = 0.007); ethyl paraben above detection level was also significantly associated (PR = 1.57, 95% CI: 1.06–2.34, p = 0.02)	[54]
28	413	Men (aged ≥ 18)	USA	BP-1, BP-2, BP-3, BP-8, 4-OHBP	Urine, blood, semen	Reproductive health, sperm quality	BP-2 exposure was significantly associated with decreased sperm concentration (β = –0.74; 95% CI: –1.41, –0.08), and BP-8 with decreased sperm viability via hypo-osmotic swelling (β = –2.57; 95% CI: –4.86, –0.29). No significant associations were found for BP-1, BP-3, or 4OH-BP	[55]
29	501 couples	Women (aged 18–44 years old) and men (aged ≥ 18 years old)	USA	BP-1, BP-2, BP-3, BP-8, 4-OHBP	Urine	Reproductive health, male fertility	Higher urinary concentrations of BP-2 in male partners were significantly associated with reduced fecundity (Fecundability Odds Ratio = 0.69, 95% CI: 0.49–0.97), indicating a 31% decrease in the odds of conception per cycle. 4-hydroxybenzophenone in males also showed reduced fecundity (FOR = 0.74, 95% CI: 0.54–1.00)	[56]
30	76	Children 49 obese and 27 non-obese (aged 2–14)	India	BP-3, 3,4-DHB	Urine	Childhood obesity	No significant associations were found between childhood obesity and BP-3. Statistically significant association found was between urinary 3,4-dihydroxybenzoic acid (3,4-DHB) levels and childhood obesity. After adjusting for age, gender, income, education, antenatal complications, and physical activity, the odds ratio was 2.08 (95% CI: 1.05–4.09, p = 0.035)	[57]
31	166	Mother-infant pairs	Iran	BP-1, BP-3, BP-8, 4-OHBP	Urine	Gestational age and neonatal size at birth	In the 1 st trimester, BP-1 showed a significant positive association with gestational age (β = 0.171, p = 0.019), while in girls, both BP-1 and BP-3 were significantly inversely associated with gestational age (β = −0.612, p = 0.034 for BP-1; β = −0.614, p = 0.034 for BP-3)	[58]
32	3,619	Mother-infant pairs	USA	BP-3	Urine	Neonatal birth weight	A 1-unit increase in log₁₀ pregnancy-averaged BP-3 and methylparaben concentrations was associated with 29% (95% CI: 5%, 58%) and 32% (95% CI: 3%, 70%) higher odds of small for gestational age (SGA), respectively; benzophenone-3 also decreased birthweight by 29.2 g (95% CI: − 58.0, − 0.4 g)	[59]
33	101	Men (aged 18–20), whose mothers during pregnancy had a serum sample analyzed	Denmark	BP-1, BP-2, BP-3, BP-7, 4-OHBP, 4-MBP	Serum (pregnant mothers), semen, blood (sons)	Reproductive health, male fertility, hormone levels	Higher prenatal exposure to BPA and BP-3 was significantly associated with increased luteinizing hormone (LH) levels in young adult males (e.g., BPA T3 vs T1: + 33% [95% CI: 10%, 62%]; BP-3 T2 vs T1: + 21% [−2%, 49%]) and a lower testosterone/LH ratio for BPA (p-trend = 0.01), indicating compensated reduced Leydig cell function	[60]
34	1690	Men (aged ≥ 18 years old)	USA	BP-3	Urine, serum	Reproductive health, sex steroid hormones	Higher urinary BP-3 was significantly associated with testosterone deficiency—e.g., quintile 3 had an OR of 2.47 (95% CI: 1.53, 3.98) vs. quintile 1—and total testosterone levels were reduced by − 12% (95% CI: − 19%, − 5%) in quintile 3 and − 9% (95% CI: − 17%, − 1%) in quintile 5	[61]
35	900	Pregnant women	USA	BP-3, TCS, MPB	Urine	Ultrasound and delivery measures of fetal growth	Higher exposure to and BP3 was associated with larger ultrasound measures of fetal growth, including larger estimated fetal weights. Triclosan (TCS) exposure was associated with a significant increase in estimated fetal weight z-score (mean difference: 0.09, 95% CI: 0.01–0.18), corresponding to a 21 g increase at 30 weeks gestation, and with higher birthweight z-scores (mean difference: 0.13, 95% CI: 0.02–0.25). Methylparaben (MPB) was significantly associated with higher odds of small-for-gestational age (SGA) birth (OR: 1.45, 95% CI: 1.06–1.98)	[62]
36	495	Women (aged 18–44)	USA	BP-3, BP-1, BP-8, BP-2, 4-OHBP	Urine, serum	Uterine leiomyoma (fibroids)	Women with uterine fibroids had significantly higher urinary concentrations of BPA (2.09 μg/g vs. 1.46 μg/g; p = 0.004), 2,4OH-BP (11.10 μg/g vs. 6.71 μg/g; p = 0.01), and 2OH-4MeO-BP (11.31 μg/g vs. 6.10 μg/g; p = 0.01), but none of these exposures were significantly associated with odds of fibroid diagnosis after adjustment (e.g., BPA aOR = 0.9, 95% CI: 0.7–1.2)	[63]
37	379	Girls (aged 6–7), every 6 months for follow-up for 10 years	USA	BP-3	Urine, blood, serum	Sex hormones, pubertal development	Reported sunscreen use was significantly associated with lower testosterone levels at thelarche: adjusted β =  − 0.0163, 97.5% CI: − 0.0300 to − 0.0026. The 2nd quartile of BP-3 urinary biomarker was associated with earlier thelarche: adjusted HR = 1.584, 97.5% CI: 1.038 to 2.415	[64]
38	501	Couples discontinuing contraception to try for pregnancy (women aged 18–44 and men aged ≥ 18)	USA	BP-1, BP-2, BP-3, BP-8, 4-OHBP	Urine, serum	Reproductive health, dependent on age, fecundability	Among women aged ≥ 35, urinary BP-2 was associated with a 39% reduction in fecundability (FOR = 0.61, 95% CI: 0.36–1.05) and 4OH-BP with a 29% reduction (FOR = 0.71, 95% CI: 0.46–1.09), though confidence intervals include 1, indicating borderline statistical significance. No significant effect modification by age was observed overall	[65]
39	143	Women (aged 18–44)	USA	BP-1, BP-3	Urine	Reproductive hormone levels	exposure to phenol and UV filter mixtures was significantly associated with decreased estradiol (β =  − 0.16, 95% CI: − 0.22, − 0.10), FSH (β =  − 0.12, 95% CI: − 0.17, − 0.07), and LH (β =  − 0.17, 95% CI: − 0.23, − 0.10). Conversely, paraben and paraben metabolite/BPA mixtures were significantly associated with increased estradiol (β = 0.21, 95% CI: 0.15, 0.28; and β = 0.12, 95% CI: 0.07, 0.18, respectively)	[66]
40	1829	Males and females	USA	BP-3, DEHP	Urine, serum	Thyroid hormone levels (T3, T4)	Urinary benzophenone-3 (BP-3) and the DEHP metabolite MEHHP were significantly associated with lower thyroid hormone levels in a general U.S. population: BP-3 was linked to decreased total T4 (β =  − 0.065, p < 0.001), and MEHHP to decreased total T4 (β =  − 0.12, p < 0.001) and increased TSH (β = 0.033, p = 0.020)	[67]
41	106	Pregnant women (aged 18–40)	USA	BP-3	Urine, blood	Reproductive and thyroid hormone levels (Estradiol, progesterone, SHBG, FT3, FT4, TSH)	An interquartile range (IQR) increase in methyl paraben was significantly associated with a 7.70% increase in sex hormone-binding globulin (SHBG) (95% CI: 1.50, 13.90; p = 0.02), and an IQR increase in butyl paraben and BP = 3 was significantly associated with an 8.46% decrease in estradiol (95% CI: –16.92, 0.00; p = 0.05) and a 5.64% increase in free thyroxine (FT4) (95% CI: 1.26, 10.02; p = 0.01)	[68]
42	1560	850 males and 710 females (over the age of 12)	USA	BP-3	Urine	Thyroid hormone levels (T3, T4, TSH)	Higher exposure to a mixture of EDCs — including BP-3 was significantly associated with lower total T4 levels in males (β =  − 0.19, 95% CI: − 0.31, − 0.05), but not in females; in females, exposure was non-significantly associated with higher T3 (β = 0.09, 95% CI: − 0.03, 0.21)	[69]
43	644	Pregnant women	China	BP‑1, BP‑3, 4-OHBP	Urine	Blood pressure status during pregnancy	Urinary BP-3 (benzophenone-3) was significantly associated with increased systolic blood pressure (SBP) in pregnant women carrying male fetuses: per ln-unit increase in BP-3, SBP increased by 0.32 mmHg (P-FDR = 0.13)	[70]
44	530	184 males (aged 18–55) and 346 females (aged 18–46)	USA	BP-3	Urine	Birth size of singleton infants	Each log-unit increase in paternal preconception BP-3 concentration was associated with a statistically significant 137 g increase in birth weight (95% CI: 60, 214; p = 0.0005)	[71]
45	386	Mother–child pairs (children at 10 years of age)	China	BP-3	Urine	Neonatal thyroid function and childhood behavioral problems aged 10 years	Higher maternal urinary BP-3 levels during pregnancy were significantly associated with poorer prosocial behavior in children at 10 years of age, with an odds ratio (OR) of 1.58 (95% CI: 1.04–2.39; p = 0.032)	[72]
46	304	Women undergoing infertility treatment (aged 18–45)	USA	BP-3	Urine	Reproductive health	Those in the highest quartile of urinary BP-3 had 51% higher implantation (p_trend = 0.02), 68% higher clinical pregnancy (p_trend = 0.01), and 75% higher live birth (p_trend = 0.02) probabilities compared to those in the lowest quartile	[73]
47	124	35 women with endometriosis (aged 20–54 and 89 healthy patients (controls)	Spain	BP-1, BP-3, 4-OHBP	Urine	Development and progression of endometriosis	Association with higher risk of endometriosis. BP-3 levels in women in the second versus first exposure tercile were significantly associated with increased endometriosis risk (adjusted OR = 4.98, p = 0.008	[74]
48	1339	Children	Spain	BP-1, BP-3	Urine	Childhood obesity	Each natural log-unit increase in urinary BP-3 (CAS-adjusted) was significantly associated with increased odds of obesity in European adolescents (OR = 1.20; 95% CI: 1.04–1.38), with a stronger effect in males (OR = 1.34; 95% CI: 1.09–1.65)	[75]
49	54	33 male and female patients with dry eye syndrome (DES) and 21 healthy patients (controls)	Brazil	BP-1, BP-2, BP-3, BP-8, 4-OHBP	Urine	Development and progression of Dry Eye Syndrome (DES)	No significant associations. BP-3 was higher in dry eye syndrome patients (GM = 10.79 ng/mL), but this difference was not statistically significant (p = 0.88)	[76]
50	217	Pregnant women	USA	BP-3	Urine, blood	Glucose levels during pregnancy among women from a fertility clinic	Higher first trimester BP-3 concentrations were significantly associated with lower mean glucose levels [Q4 vs. Q1: 103.4 mg/dL (95% CI: 95.0, 112.5) vs. 114.6 mg/dL (95% CI: 105.8, 124.2); p = 0.02], and second trimester BP-3 concentrations were linked to lower odds of abnormal glucose [Q3 vs. Q1 OR = 0.12 (95% CI: 0.01, 0.94); p = 0.04]	[77]
51	476	Pregnant women	USA	BP-3	Urine	Fetal growth (birth length, weight)	Interquartile range (IQR) increase in benzophenone-3 (BP-3) was associated with a 0.26 standard deviation decrease in abdominal circumference z-score (95% CI: − 0.44 to − 0.08) in female foetuses	[78]
52	339	Men	USA	BP-1, BP-2, BP-3, BP-8, 4-OHBP	Seminal plasma	Semen quality	BP-3 in seminal plasma was not significantly associated with adverse semen quality outcomes. Specifically, being above the 75th percentile for BP-3 was associated with lower odds of having normal semen volume (OR = 0.55; 95% CI: 0.21–1.48), but this was not statistically significant (FDR-adjusted p-value > 0.05). BP-2 had the only notable and consistent (though modest) adverse effects on sperm motility traits across both urine and seminal plasma	[79]
53	452	Mother-son pairs (boys at age 5)	France	BP-3	Urine	Intelligence quotient (IQ) of boys	No statistically significant association between in-utero exposure to phenols or phthalates and boys’ IQ at age 5–6	[80]
54	993	Mother-son pairs (boys at age 3.1 and 5.6 years old)	France	BP-3	Urine	Childhood behavioral problems at the age of 3–6 years	No association of prenatal exposure to BP-3 with behaviour	[81]
55	1239	Girls (aged 6–8)	USA	BP-3	Urine	Pubertal development in girls	BP-3 exposure was associated with significantly delayed breast development: girls in the highest quintile had a hazard ratio (HR) of 0.80 (95% CI: 0.65–0.98), indicating a 5–6 month later onset of breast development compared to the lowest quintile	[82]
56	200	Girls (first samples—aged 6.7 to 9.6 years; second samples—aged 9.4 to 13.1)	Chile	BP-3	Urine	The age of menarche in girls	A log(ng/ml) increase in prepubertal (Tanner 1) benzophenone-3 (BP-3) was significantly associated with earlier menarche (HR: 1.17; 95% CI: 1.06–1.29), indicating a 17% increased hazard of menarche per log unit increase in BP-3	[83]
57	8498	Males and females with diabetes (aged ≥ 20 years old)	USA	BP-3	Urine	Diabetes	Higher urinary benzophenone-3 (BP-3) concentrations were significantly associated with lower odds of diabetes: odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.61–0.79 (comparing the 75th to the 25th percentile, adjusted for multiple confounders)	[84]
58	NAD	Men	Denmark	BP-3, BP-4, BP-5, BP-8	Semen	Acrosome reaction, penetration, hyperactivation, and viability in human sperm cells	BP-3 induced a significant Ca2⁺ signal in human sperm, with a mean relative maximal signal of 38.19% of the progesterone-induced signal at 10 μM. It also competitively inhibited the progesterone-induced Ca2⁺ response, shifting the EC₅₀ of progesterone to higher concentrations, indicating interference with progesterone signalling	[85]
59	423	101 Hirschsprung’s disease (HSCR) patients’ mothers and 322 healthy mothers (controls)	China	BP-3	Urine	Hirschsprung’s disease (HSCR)	Maternal BP-3 exposure was significantly associated with an increased risk of Hirschsprung’s disease in offspring, with adjusted odds ratios (ORs) of 2.39 (95% CI: 1.10–5.21) for medium and 2.61 (95% CI: 1.15–5.92) for high BP-3 exposure levels (p for trend < 0.05)	[86]
60	7114	7114 participants including 807 Osteoarthritis (OA) patients (aged ≥ 20 years old)	USA	BP-3	Urine	Osteoarthritis (OA)	Urinary BP-3 levels were positively associated with osteoarthritis prevalence: participants in tertile 2 had an OR = 1.55 (95% CI: 1.17–2.06, FDR-adjusted P = 0.012) and tertile 3 had an OR = 1.66 (95% CI: 1.23–2.24, FDR-adjusted P = 0.006) compared to tertile 1	[87]
61	157	Children, 69 male and 88 female (aged 3–17)	U.K	BP-3, BP-4	Skin	Allergic contact dermatitis	6.4% of children had photoallergic (PA) reactions to UV-filters and/or sunscreen products, with benzophenone-3 being the most common culprit (causing 33% of the PA responses, i.e., 3 out of 9 UV-filter-related reactions)	[88]
62	155	Men (aged 18–55)	China	BP-1, BP-2, BP-3, BP-6, 4-OHBP, 2,3,4-OHBP	Semen	Reproductive health, semen quality	Co-exposure to six top-ranked EDCs—including BP-3 was significantly associated with reduced sperm total motility (β =  − 0.18, 95% CI: − 0.29 to − 0.07, P = 0.002) and progressive motility (β =  − 0.27, 95% CI: − 0.43 to − 0.10, P = 0.002); while BP-3 showed borderline significance individually, it contributed to the adverse mixture effect identified by the quantile-based g-computation model	[89]
63	306	Mother–child pairs (children aged 4–5)	Spain	BP-1, BP-2, BP-3, BP-6, BP-8, 4-OHBP	Placenta	Cognitive functioning in preschool children	BP-3 was detected in less than 9% of placenta samples and was not included in the exposure-outcome analyses, meaning no effect size or significance for BP-3	[90]
64	478	Mother–child pairs (children aged 2 years old)	China	BP-1, BP-3, 4-OHBP	Urine	Neurocognitive development in 2 years old children	A twofold increase in prenatal 4-hydroxybenzophenone (4-OH-BP) was associated with a − 2.96 decrease in boys’ psychomotor development index (PDI) scores (95% CI: − 4.48, − 1.45; Psex-int = 0.01), while no significant association was found for BP-3	[91]
65	338	Mother–child pairs (children pubertal timing was assessed every 9 months between ages 9 and 13 in 179 girls and 159 boys)	USA	BP-3	Urine	Pubertal development	No significant associations	[92]
66	159	Mother–child pairs	USA	BP-3	Urine	Respiratory and allergic diseases: asthma, wheeze and atopic skin conditions	In adjusted models, prenatal exposure to benzophenone-3 (BP-3) was inversely associated with childhood percent fat mass in girls (β per SD =  − 1.51, 95% CI: − 3.06 to 0.01), but not in boys (β per SD =  − 0.20, 95% CI: − 1.69 to 1.26), indicating a potential sex-specific antiadipogenic effect	JP [53]
68	300	Children aged 6 to 14 years	Brazil	BP-1, BP-2, BP-3, BP-8, 4-OHBP	Urine	DNA damage	Urinary BP-3 concentrations had a geometric mean (GM) of 3.71 ng/mL and were significantly associated with increased oxidative DNA damage, as measured by 8OHDG (correlation coefficient r = 0.158–0.359, p < 0.05)	[93]
69	373	Pregnant women	USA	Self-reported sunscreen usage frequency	Survey	Blood glucose levels during pregnancy	Higher frequency of sunscreen use was associated with increased blood glucose levels in pregnant women, particularly in mid-pregnancy. Frequent sunscreen use: + 3.4 mg/dL higher glucose (95% CI: + 0.8, + 6.0) in mid-pregnancy	[94]

NAD−no available data; BP−benzophenone; BP−1−benzophenone−1; BP−2−benzophenone−2; BP−3−benzophenone−3; BP−4−benzophenone−4; BP−5−benzophenone−5; BP−8−benzophenone−8; 4−OHBP−4‑hydroxy‑benzophenone; 4−MBP−4‑methyl‑benzophenone; 2,3,4−OH−BP−2,3,4−trihydroxybenzophenone; TT−testosterone; FSH−follicle−stimulating hormone; LH−luteinizing hormone; T/E2−testosterone/estradiol ratio; T3−triiodothyronine; FT3−free triiodothyronine, thyroxine−T4; FT4−free thyroxine; IGF−I−insulin−like growth factor; TSH−thyroid stimulating hormones; SHBG−sex hormone−binding globulin; AMH−Anti−Müllerian hormon

Benzophenone-4

BP-4 is a sulfonic acid derivative of BP-3 being a broad-spectrum UV filter. Known as sulisobenzone with chemical name 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid. Benzophenone-5 is the sodium salt form of benzophenone-4 [95]. In the EU these two BPs are permitted for use as a UV filter in sunscreen products at concentrations up to 5% (SCCS opinion on BP-4) [96], and up to 10% in Australia and US [27, 97].

Benzophenone-8

Also called as dioxybenzone with chemical name 2,2′-dihydroxy-4-methoxy benzophenone being very similar structurally to BP-3 with one additional hydroxyl group. BP-8 is not allowed to be used in cosmetics in the EU [10], but can be used at maximum concentration of 3% in the US and Australia [11, 27, 98].

Benzophenone Derivatives – Health Impact

Hormone Levels

The most common method for studying the endocrine disrupting properties of UV filters as well as many different substances is monitoring changes in blood hormone levels. In women, A Beck et al., (2024) reported increased levels of testosterone, intrafollicular sex hormone-binding globulin (SHBG), estradiol and Anti-Müllerian hormone (AMH) [51]. Another article from A Pollack et al., (2018) reported that higher exposure to BP-1, BP-3 are associated with decreased estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) [66]. BP-3 also altered with thyroid hormone levels, causing decreased serum and urinary triiodothyronine (T3) and thyroxine (T4) [67].

Several studies have examined hormone levels among pregnant women, as this factor can impact neonatal health since infants are exposed to organic UV filters in utero. A Aker et al., 2016 found an association between BP-3 exposure and decrease in T3 which was confirmed by subsequent study [49]. For higher maternal serum concentrations of 4-OHBP M Krause et al., 2018 reported increased T3, T4, insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 [22]. Also co-exposure to different BPs (BP-1, BP-2, BP-3, BP-8, and 4-OH-BP) was found to correlate with decreased levels of thyroid stimulating hormone (TSH), glucose, as well as increased serum creatinine levels (Cr) in pregnant women [35]. Z Wang et al., 2020 report a time-specific relationship between BP-3 and lower glucose levels during pregnancy in subfertile women [77]. There was also a positive association between BP-3 and T4 levels in newborns [52].

Higher urinary concentration of BP-3 in men was reported to be associated with decreased testosterone in adolescent boys [30], and adult men [61] along with decreased estradiol and SHBG. In young men with filaggrin (FLG) gene mutations—known to impair skin barrier integrity and increase dermal permeability—urinary levels of BP-1, BP-3, and 4-OHBP were associated with higher circulating testosterone and estradiol and lower follicle-stimulating hormone (FSH) concentrations [32]. Another study reports association between urinary BP-1 and BP-3 concentrations and higher FSH [38]. BP-1 was also found out to be associated with increased testosterone/estradiol ratio and decreased inhibin b/FSH ratio. S Kim et al., 2017 also found an association between higher BP-3 exposure and decreased serum and urinary T3 and T4 levels in men as well [67]. Increased levels of luteinizing hormone (LH) in adult males were observed with higher prenatal exposure to BP-3 [60]. Co-exposure to multiple EDCs including BP-3 was associated with total T4 in males but not in females [69].

Reproductive Health

Co-exposure to multiple EDCs including BP-3 was associated with self-reported infertility [54] and longer time-to-pregnancy for women ≥ 35 years old, however this study also reported that age did not modify the relation between co-exposure to EDCs including BP-type filters and fecundability [65]. For women who underwent in vitro treatment, higher exposure to BP-3 was not related to total oocyte count, fertilization, implantation rate, clinical pregnancy, and live birth [50]. For women who underwent infertility treatments no significant associations were found between measures of ovarian reserve and BP-3 exposure [99].

In men, co-exposure to multiple EDCs including BP-1 and BP-3 was associated with deteriorated sperm quality [99]. A variety of BPs (BP-1, BP-2, BP-3, BP-8, 4-OHBP) detected in seminal plasma were inversely associated with sperm motility [100]. BP-2 was reported to influence decreases in the percent of sperm with straight and linear movement, diminished sperm concentration, more immature sperm, and a decreased percentage of other tail abnormalities (Fig. 3) [55, 100]. This study also reported that BP-8 was associated with decreased hypo-osmotic swelling and higher acrosome area [55]. In another study of G Louis et al., 2014, where connection between urinary concentrations of BP-type filters and couples’ fecundity was examined, male partners’ concentrations of BP-2 and 4-OHBP were associated with reduced fecundity in adjusted models [56]. In models adjusting for both partners’ concentrations, male BP-2 concentration remained associated with reduced fecundity. For 4-OHBP, urinary levels might be associated with a decrease in sperm DNA fragmentation index. Although, the authors emphasize that effects observed were likely to be small and of uncertain clinical significance [48].

Fig. 3.

Schematic representation of the biological matrices assessed in studies investigating the endocrine-disrupting effects of BP-3 in sunscreen products with confirmed presence of BP-3 and its metabolites (Tables 1 and 2)

There are also findings where BP-type UV filters did not influence sperm parameters. For instance, studies have reported no significant associations between urinary concentrations of BPs (BP-1, BP-2, BP-3, BP-4, BP-5, BP-8, 4-OHBP) and any semen quality parameters [38] [33]. However, BP-3 and 4-MBP has been shown to induce Ca²⁺ signals in human sperm cells, potentially interfering with the fertilization process by activating the sperm-specific CatSper Ca²⁺ channel [85]. Additionally, high prenatal exposure to BP-3 was associated with compensated reduced Leydig cell function, although no other markers of male reproductive health in adulthood were affected [60].

Prenatal and Neonatal Effects

Prenatal effects refer to the impacts on the developing fetus during pregnancy, while neonatal effects pertain to the health and development of the newborn in the initial weeks after birth. These stages are critical because they involve rapid growth and development, where any disruptions can lead to lasting health issues. The findings present varied and sometimes contradictory effects. Higher BP-3 exposure was associated with increased placental weight at birth and placental-fetal ratio (PFR) [29] and larger ultrasound measures of fetal growth, such as estimated fetal weights [62]. Additionally, increased paternal preconception BP-3 concentration was linked to a 137 g increase in birth weight [71]. Contrarily, BP-1 and BP-3 were associated with decreased birth weight and length in girls [40], and BP-3 was linked to reduced birth weight and chest circumference during pregnancy [35, 59, 78]. For 4-OHBP, male infants of mothers in the middle exposure group had lower birth weight and shorter head and abdominal circumferences compared to those in the low exposure group [44]. Moreover, BP-3 exposure showed a relationship with variations in gestational age, with some studies indicating an increase in gestational age [42], while others reported association between BP-3 and BP-1 and decreased gestational age in girls which likely contributed to lower birth weight in girls compared to boys [58]. H Liu et al., 2019 showed the potential of BPs to alter the blood pressure in pregnant women with stronger effects observed in those carrying male foetuses [70]. In a study of J Bae et al., 2016 where connection between urinary concentrations of BP-type filters and ratio of males to females at birth was examined maternal urinary concentrations of 4-OHBP were linked to a higher incidence of male births, while both maternal and paternal BP-2 concentrations were associated with a higher incidence of female births [36].

Puberty and Development

Puberty and development refer to the critical stages in human growth when individuals transition from childhood to adulthood, marked by significant physical, hormonal, and psychological changes that can be disrupted by EDCs including UV filters, leading to long-term implications for reproductive health, growth, and the risk of developing chronic diseases later in life.

Y Zhou et al., 2023, identified an association between BP-2 exposure and earlier pubertal development in girls, and AM Binder et al.,2018. linked increased pre-pubertal levels of BP-3 to early menarche [31, 36]. C Giannini et al., 2022, found an association between higher BP-3 urinary concentration and an earlier onset of thelarche, but another study reported delayed breast development by 5–6 months [64, 83].

In boys, BP-3 exposure was associated with delayed pubertal development [39]. However, KG Harley et al., 2019 found no significant associations between BP-3 and pubertal development in both boys and girls [92]. Philippat et al., 2017, reported no association between prenatal BP-3 exposure and behavior in boys aged 3–6 years, although it was linked to poorer prosocial behaviors at age 10 [81]. D Nakiwala et al., 2018, found no link to IQ in boys at age 5 [80]. Urinary 4-OHBP was associated with child neurocognitive development and lower psychomotor development index (PDI) scores among boys [91]. Freire et al., 2020, suggested a possible protective effect of 4-OHBP on gross motor skills in children aged 4–5 years old [90].

Regarding childhood obesity, studies presented varying results. P Wang et al., 2022, found lower adiposity measures in peripubertal boys but not in girls for BP-2 and BP-3 in children aged 7–15 years old, while J Buckley et al., 2016, noted a weak association between BP-3 exposure and lower percent fat mass in girls only for children aged 4–9 years old [41, 53]. B Wang et al., 2023 reported an inverse association between co-exposure to BPs and childhood obesity [46]. In contrast, J Xue et al., 2015 found no significant associations between childhood obesity and BP-3 exposure [57].

Disease Related Outcomes

Several studies also examined the influence of BP-type UV filters on certain diseases. FM Peinado et al., 2021; 2023, reported a positive association between BP-1, BP-3, and 4-OHBP with the development and progression of endometriosis [57, 74]. In the context of type 2 diabetes, AJ Li et al., 2018, found that 4-OHBP exposure was positively associated with an increased risk of diabetes, while JB Ward et al., 2020, observed that higher concentrations of BP-3 were associated with lower odds of developing diabetes [34, 43]. H Kang et al., 2019, identified a strong association between BP-1 and an increased urinary albumin-to-creatinine ratio (ACR), a key marker of kidney function [47]. Maternal exposure to BP-3 was linked to an increased risk of Hirschsprung’s disease (HSCR) in children [86]. BP-3 was also positively associated with the prevalence of osteoarthritis [87]. Furthermore, BP-3 was identified as the most common UV filter responsible for photoallergic contact reactions [88].

In contrast, other studies found no significant associations between BP-type UV filters and certain health outcomes. J Gu et al., 2019, reported no significant associations between BP-3 and polycystic ovary syndrome (PCOS) [37].There were no significant association between BP-1, BP-2, BP-3, BP-8, or 4-OHBP with the odds of developing uterine fibroids [66] and dry eye syndrome [76].

Classification of Other Organic UV Filters

4-Aminobenzoic Acid

4-Aminobenzoic Acid (PABA) and its esters are effective mainly against UVB radiation and slightly against UVA radiation. PABA penetrates the stratum corneum and can bind to its proteins through hydrogen bonding. Consequently, it may continue to provide protection even after bathing, swimming, or sweating. Its use in cosmetics has declined over the years due to its low photostability and the associated risks of causing allergies, skin irritation, and contact dermatitis in some individuals [102]. Approved for use only in the US in concentration up to 15% (U.S. Food and Drug Administration. Sunscreen Drug Products for Over-the-Counter Human Use; Final Monograph. Federal Register, Vol. 64, No. 98, May 21, 1999, pp. 27,666–27,693). 2-Ethylhexyl 4-(dimethylamino)benzoate (INCI) known also as Padmiate O (USAN) or Ethylhexyl Dimethyl PABA (OD-PABA, IUPAC) is one of PABA esters allowed to use up to 8% in Australia (Therapeutic Goods Administration (TGA). Australian Regulatory Guidelines for Sunscreens. Department of Health, Australian Government, August 2021), EU (European Parliament and Council of the European Union. Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on Cosmetic Products. Official Journal of the European Union, L 342, November 22, 2009, pp. 59–209), and US (U.S. Food and Drug Administration. Sunscreen Drug Products for Over-the-Counter Human Use; Final Monograph. Federal Register, Vol. 64, No. 98, May 21, 1999, pp. 27,666–27,693) in all types of cosmetic products. Another ester is Ethoxylated ethyl-4-aminobenzoate (INCI) also identified in the literature as polyethylene glycol, PEG-25 PABA (IUPAC) is approved in EU and Australia up to 10% but not in the US.

Benzylidenecamphor Derivatives

4-Methylbenzylidene Camphor (4-MBC) is a UVB filter approved for use in EU and Australia up to 4% but not in the US. 4-MBC is persistent and bioaccumulative being an important environmental contaminant [103]. Due to evidence of endocrine disrupting properties of its unmethylated derivate (3-benzylidene camphor) it was banned for use in cosmetics products in 2018 (European Commission. Commission Implementing Decision (EU) 2018/2013 of 14 December 2018 on the Harmonised Standards for Cosmetics Products Drafted in Support of Regulation (EC) No 1223/2009 of the European Parliament and of the Council. Official Journal of the European Union, L 322, December 17, 2018, pp. 14–19.). Benzylidene Camphor Sulfonic Acid is considered a low-risk substance and can be added to cosmetics in EU and Australia up to 6% and in US up to 4%. Camphor Benzalkonium Methosulfate with a trade name Mexoryl SO, is approved for use in Australia and the EU up to 6% in sunscreen products. Terephthalylidene Dicamphor Sulfonic Acid or Ecamsule is the only UVA filter from benzylidenecamphor derivatives. Approved in EU and Australia up to 10%. It is not accepted by the FDA in the US, although this filter can be found in some sunscreens available on the US market such as “Anthelios SX” [104]. Polyacrylamidomethyl Benzylidene Camphor also known under the trade name Mexoryl SW is approved only in the EU up to 6%.

Benzimidazole and Benzotriazole Derivatives

Phenylbenzimidazole Sulfonic Acid known also as ensulizole is an UVB filter approved for use in EU and Australia up to 8% and 4% respectively. Bastien et al., 2010 reported that ensulizole suppressed the formation of cyclobutane pyrimidine dimers after UVB exposure, but also caused the formation of oxidized guanines after UVA or UVB exposure by photosensitization [105]. Disodium Phenyl Dibenzimidazole Tetrasulfonate or Bisdisulizole disodium as a trade name is a dimer analog of ensulizole approved in EU and Australia up to 10%. It has big molecular weight (674.57 g/mol), and hydrophilic properties, therefore it has a very low skin penetration and a good safety profile [9]. Drometrizole Trisiloxane (DTS) or Silatrizole is a photostabile, broad-spectrum UV filter approved for use in EU and Australia up to 15% and 10% respectively. Methylene Bis-benzotriazolyl Tetramethyl butylphenol is a broad-spectrum UV filter known as bisoctrizole or MBBT, used in the EU and Australia at concentrations up to 10%. MBBT demonstrates very low dermal absorption and is considered safe at recommended concentrations (European Commission, Directorate-General for Health and Food Safety. Opinion on 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)−4-(1,1,3,3-tetramethylbutyl)phenol) (Nano Form) – Submission III – COLIPA S79. European Commission, 2015).

Cinnamic Acid Derivatives

Esters of cinnamic acid derivatives are relatively similar structurally to the benzylidenecamphor derivatives and are considered as an alternative to PABA derivatives. All compounds from this group are the UVB absorbers. Isopentyl 4-Methoxycinnamate known as amiloxate (INN) together with ethylhexyl methoxycinnamate are allowed in the EU and Australia in maximum allowed concentrations of 10%, while Ethylhexyl Methoxycinnamate also referred as octinoxate (INN) is also allowed in the US up to 7%. Octinoxate is not allowed for use in a state of Hawaii due to high influence on the marine ecosystem [106]. 2-Ethoxyethyl 4-methoxycinnamate or cinoxate has similar chemical properties to octinoxate and amiloxate and is allowed for use in US and Australia in a concentration up to 3 and 6% respectively, but it is not authorized in the EU. Another compound from this group is octocrylene allowed in the US, Australia and EU up to 10% in cosmetics. It has been reported that octocrylene transforms over time leading to the formation of benzophenone [107]. Potential health risks connected to this occurrence needs further research.

Dibenzoylmethane Derivatives

The only compound belonging to this class is butyl methoxydibenzoylmethane better known as avobenzone. It’s a popular UVA filter willingly added to sunscreen products to enhance the formula for broad-spectrum protection. It can be used in the EU, Australia and US at concentrations up to 5% or 3%. Due to being oil-soluble and with a low molecular weight (310.4 g/mol) avobenzone easily penetrates the skin. Although, the FDA considers this compound as a group III of GRASE, meaning that its impact on health needs further research but in the meantime, it is not being considered as unsafe.

Salicylic Acid Derivatives

Salicylates absorb weakly UVB radiation, hence they are often used in mixture with other UV-filters, such as UVA filter avobenzone to extend spectrum and duration of protection due to their photostability. Ethylhexyl Salicylate (IUPAC) also known as octisalate is approved up to 5% in Australia, EU and US. Homomenthyl Salicylate (IUPAC), a structural analog, also referred to as homosalate can be added to cosmetics up to 10% in EU and 15% in Australia and US. It is widely used in sunscreen products in the US [108].

Triazine Derivatives

The UV filters from this class that share a triazine ring, including Ethylhexyl Triazone, Diethylhexyl Butamido Triazone (iscotrizinol), Bis-ethylhexyloxyphenol Methoxyphenyl Triazine (bemotrizinol, anisotriazine), Tris-biphenyl Triazine, and Phenylene Bis-diphenyltriazine, are primarily approved in the EU with varying maximum concentrations, ranging from 5 to 10% (European Parliament and Council of the European Union. Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on Cosmetic Products. Official Journal of the European Union, L 342, November 22, 2009, pp. 59–209). These compounds are known for their high photostability, low skin penetration due to high molecular weight and effectiveness in protecting against both UVA and UVB radiation [109]. Bemotrizinol, iscotrizinol and tris-biphenyl triazine are approved in Australia also (Therapeutic Goods Administration (TGA). Australian Regulatory Guidelines for Sunscreens. Department of Health, Australian Government, August 2021). Despite their safety profiles, none are approved in the US. Innovations such as encapsulation in lipid carriers and nanostructured formulations enhance their effectiveness and minimize potential skin absorption.

Other Compounds

Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate with abbreviation MCE and commercial name Mexoryl 400 is the UVA filter belonging to cyclic merocyanines class. Allowed in the EU at concentrations up to 3% but only in cosmetics that will not lead to exposure of the end-user’s lungs via inhalation (European Commission, Directorate-General for Health and Food Safety. Opinion on 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)−4-(1,1,3,3-tetramethylbutyl)phenol) (Nano Form) – Submission III – COLIPA S79). European Commission, 2015). Another UVA filter is menthyl anthranilate known also as meradimate. Chemically similar to the PABA derivatives. Approved in the US and Australia to be used in cosmetics at concentrations up to 5%. Dimethicodiethylbenzalmalonate or Polysilicone-15 is one of the derivatives of cinnamic acid that protects from UVB radiation. Due to high molecular weight (over 6000 g/mol) it penetrates the skin at a low level [110]. Approved in the EU and Australia for use in sunscreen formulations at a concentration up to 10%.

Other Organic UV Filters/Organic UV Filters from other Classes

There was limited availability of studies that examined the influence of UV filters from other chemical classes, thus gathered information was summed up in Table 2.

Table 2.

Exposure to organic UV filters from different chemical classes and health outcomes reported in included studies

No	No. of participants	Population	Country/area	Analytes	Matrix (research material)	Research endpoints	Conclusion	Reference
1	223	113 boys with a mean age of 10.9 years, and 110 girls with an average age of 10 years old	China	4’-MAP. OD-PABA	Urine	Pubertal development	UV filters (BP-3, OD-PABA, and 4′-MAP) were associated with decreased pubertal development stages in boys	[101]
2	40 women with polycystic ovary syndrome (PCOS), and 83 healthy women (controls)	Women with PCOS (aged 20–41)	China	HMS, OC	Urine	Development and progression of PCOS	OC was significantly associated with PCOS in women with BMI ≥ 24 thus there is positive association between OC and PCOS risk in obese and overweight women	[37]
3	521	High school-age boys and girls	China	4’-MAP, EHMC, OD-PABA, 4-MCA, 4-MBC, OC, 3-BC	Urine	Pubertal development	EHMC and 4′-MAP were associated with later pubertal stages and onset in boys. OD-PABA were associated with earlier pubertal stages, onset and accelerated progression in girls	[39]
4	195	65 men genotyped for FLG R501X, 2282del4, and R2447X loss-of-function mutations, 130 non-carriers (controls)	Denmark	4-MBC, 3-BC	Urine, blood, semen	Semen quality and reproductive hormones (FSH, LH, SHBG, TT, inhibin B, and estradiol)	No significant associations	[32]
5	NAD	Men	Denmark	4-MBC, 3-BC, Meradimate, Octisalate, BCSA, HMS and OD-PABA	Semen	Acrosome reaction, penetration, hyperactivation, and viability in human sperm cells	Similar to progesterone, the UV filters 4-MBC, 3-BC, Meradimate, Octisalate, BCSA, HMS and OD-PABA induced acrosome reaction; sperm penetration into a viscous medium was increased by 3-BC	[33]
6	327	Children (aged 7–15)	China	OD-PABA, EHMC, 4-MCA, 4’-MAP	Urine	Adiposity measures in peripubertal children	EHMC was identified as the most important contributor to lower adiposity measures. No significant effects were found in girls	[41]
7	504	Children (aged 6–9)	China	PABA-E, Octisalate, HMS, EHMC, Amiloxate, OC, 4-MBC	Urine	Childhood obesity	Urinary EHMC concentrations and childhood obesity were positively associated for girls thus EHMC exposure may be an environmental obesogen for girls	[46]
8	157	Children aged 3–17 years old, 69 male and 88 female	UK	Octinoxate, OD-PABA, Avobenzon, 4-MBC, Amiloxate, Ensulizol	Skin	Allergic Contact Dermatitis	The commonest UV-filter responsible for photoallergic contact reactions (PA) was BP-3 and Octinoxate	[88]
9	300	Men	Denmark	4-MBC, 3-BC	Urine, serum, semen	Reproductive health	4-MBC, 3-BC activated the human sperm-specific CatSper Ca2+ channel in an in vitro model	[21]

4-MBC—4-Methylbenzylidene camphor; 3-BC—3‑benzylidene camphor; 4’-MAP—4’-methoxyacetophenone; 4-MCA—4-methoxycinnamic acid; OC—Octocrylene; Meradimate—Menthyl anthranilate; Amiloxate—Isoamyl P-methoxycinnamate; Octisalate—Ethylhexyl salicylate; BCSA—Benzylidene camphor sulfonic acid; HMS—Homosalate; OD-PABA—Ethylhexyl dimethyl PABA; PABA-E—2-Ethylhexyl 4-aminobenzoate; Octinoxate—Ethylhexyl methoxycinnamate; Avobenzone—Butyl methoxydibenzoylmethane; DHHB—Diethylamino hydroxybenzoyl hexyl benzoate; CBM—Camphor benzalkonium methosulfate; Drometrizole trisolane—Drometrizole trisiloxane; Iscotrizinol—Diethylhexyl butamido triazone; Bemotrizinol—Bis-ethylhexyloxyphenol methoxyphenyl triazine; Ensulizol—Phenylbenzimidazole sulfonic acid; Bisdosulizole—Disodium phenyl dibenzimidazole tetrasulfonate; Ecamsule—Terephthalylidene dicamphor sulfonic acid; NAD—no available data;

Reproductive Health

4-Methylbenzylidene Camphor (4-MBC), 3-benzylidene camphor (3-BC), Meradimate, Octisalate, Benzylidene camphor sulfonic acid (BCSA), Homosalate (HMS), and Ethylhexyl dimethyl 4-Aminobenzoic Acid (OD-PABA) were reported to induce acrosome reaction similar to progesterone, with 3-BC notably increasing sperm penetration into a viscous medium [33]. Additionally, 3-BC and BCSA were observed to competitively inhibit progesterone-induced Ca2 + signals, indicating that these UV filters may target areas within the progesterone binding pocket [85]. Further, 4-MBC and 3-BC were shown to activate the human sperm-specific CatSper Ca²⁺ channel in an in vitro model [21]. However, in another study, no significant associations were found between the 3-BC, and semen quality or reproductive hormones in men [32].

Puberty and Development

UV filters such as EHMC, OD-PABA, and 4′-MAP were associated with delayed pubertal development in boys [39, 46] while OD-PABA was associated with earlier pubertal development in girls [16]. EHMC was identified as a significant contributor to lower adiposity measures in boys, with no significant effects observed in girls in children aged 7–15 years old [41] although, subsequent study by B Wang et al., 2023, report that urinary EHMC concentrations were positively associated with childhood obesity in girls in children aged 6–9 years old [46].

Disease Related Outcomes

J Gu et al., 2019, found positive association between octocrylene and increased risk of polycystic ovary syndrome (PCOS) in women with a BMI of 24 or higher [37].

Discussion

Organic ultraviolet (UV) filters in sunscreens are a cornerstone of skin protection strategies, preventing sunburn, photoaging, and carcinogenesis. However, emerging evidence particularly for BP-3 points to its potentially endocrine-disrupting properties, raising concerns about their safety for human health and the environment. While recent reviews such as Vitale et al. (2023) have rigorously evaluated BP-3 in isolation, the present systematic review extends this framework to a broader range of organic UV filters and organizes findings thematically across critical life stages, thereby offering a population-level perspective on cumulative and class-wide endocrine effects [28]. The hormonal effects of benzophenone derivatives, particularly BP-3, dominate the literature. Several studies highlight its potential for endocrine disruptions, especially in adolescents and pregnant women. Scinicariello and Buser (2016) found that BP-3 exposure correlates with a 12% reduction in testosterone levels in adolescent boys, with no significant changes observed in girls [30]. Huang et al. (2020) reported delayed genital and pubic hair development in boys with higher BP-3 exposure, reflecting a delay of approximately 4–5 months in pubertal milestones [39]. Conversely, early menarche was observed in girls exposed to higher levels of BP-3, with Binder et al. (2018) attributing this to a 6-month advancement in the age of menarche [83]. For pregnant women, Aker et al. (2018) reported a 15% decrease in T3 levels associated with BP-3 exposure, with co-exposure to multiple benzophenones resulting in reduced thyroid-stimulating hormone (TSH) and glucose levels, as well as elevated creatinine [68]. In addition to biomonitoring studies, one cohort study directly linked self-reported sunscreen usage patterns to metabolic outcomes: Bellavia et al. (2019) observed that higher frequency of sunscreen use was significantly associated with increased blood glucose levels in pregnant women, particularly during mid-pregnancy. This supports the relevance of usage-based exposure metrics even in the absence of internal dose biomarkers [94]. In another recent studies Fu et al. (2024) and Long et al. (2019) reported inverse associations between BP-3 exposure and fetal growth metrics (e.g., birth weight, head circumference), especially during the third trimester [35, 40]. Contrastingly, Bommarito et al. (2024) identified larger fetal growth metrics with higher BP-3 exposure [62]. BP-3 exposure was also linked to altered gestational age [42, 58] and thyroid hormone levels in neonates [52]. Mixed results were found for neonatal and birth outcomes—Philippat et al. (2019) observed a 10% increase in placental-to-birth weight ratio associated with BP-3 exposure whereas, contrarily, Fu et al. (2024) linked third-trimester BP-3 levels to a 5% reduction in neonatal birth weight and chest circumference [35, 81].

Gender differences in hormonal responses are notable. In young men, BP-1 and BP-3 exposure was linked to a 10% increase in testosterone and estradiol levels in carriers of filaggrin gene mutations, alongside a reduction in follicle-stimulating hormone (FSH) [32]. Contrastingly, among adult men without genetic predispositions, higher urinary BP-3 concentrations were associated with a 15% reduction in total testosterone [61]. In addition, Peinado et al. (2021, 2023) identified a strong association between BP-3 exposure and endometriosis progression, with upregulated expression of endometrial proliferation genes. Women with the highest urinary BP-3 levels exhibited a 25% greater risk of disease exacerbation [34, 74].

The association between benzophenone exposure and fertility outcomes varied across multiple studies For male fertility: Buck Louis et al. (2015) demonstrated that BP-2 exposure reduced sperm motility by 18%, with a 10% increase in DNA fragmentation observed in seminal plasma samples with elevated 4-OHBP concentrations [48, 55]. Joensen et al. (2018) found elevated serum testosterone and estradiol with lower FSH levels in FLG mutation carriers exposed to BP-3, suggesting hormonal dysregulation [32]. Tao et al. (2022) reported increased testosterone deficiency risk among men with high urinary BP-3 levels [61]. Conversely, Rehfeld et al. (2018) and Silva et al. (2024) observed no significant associations with semen quality or ovarian reserve, respectively [33]. For female fertility: Pollack et al. (2022) found a 20% increase in time-to-pregnancy in women aged ≥ 35 exposed to BP-3, although no association with ovarian reserve measures was detected [45, 65]. BP-3 exposure was linked to gene expression changes associated with endometriosis [34] and increased intrafollicular SHBG, estradiol, and testosterone levels [51]. However, Radwan et al. (2023) found no significant impact on in vitro fertilization outcomes [50]. Additionally, several studies indicated BP-3’s negative impact on thyroid hormones. Aker et al. (2016, 2018) and Kim et al. (2017) observed decreased T3 and T4 levels associated with BP-3 exposure [49, 67, 68].

The collective evidence suggests BP-3 has potential endocrine-disrupting properties, with observed effects on reproductive health, fetal development, thyroid function, and pubertal timing. However, inconsistencies across studies possibly due to differences in study design, exposure assessment, and population demographics highlight the need for standardized, longitudinal studies to clarify BP-3’s risk profile. Given its ubiquity in sunscreen products, regulatory reviews and public health guidelines should consider these findings to balance UV protection with potential endocrine risks. Additionally, UV filters are frequently used in other cosmetic products, including makeup, moisturisers, shampoos, hand sanitizers, and hairsprays. BP-3 additionally serves as indirect food additive, and fragrance enhancer. Textiles and clothing are another possible pathway of dermal exposure to UV filters increasing the risk of indirect exposure.

Limitations and Future Considerations

An important methodological consideration across included studies is the potential for residual confounding by factors such as seasonality, outdoor physical activity, and dietary or socioeconomic patterns. These variables may co-vary with sunscreen use—e.g., more frequent use during summer months, by physically active individuals, or in higher-income populations—and may independently influence endocrine or reproductive outcomes. While some studies adjusted for season or physical activity (e.g., Joensen et al. 2018; Philippat et al. 2021), adjustment practices were inconsistent across studies. As such, interpretation of associations between UV filter exposure and health outcomes should be approached with caution, particularly when confounder control is limited or poorly reported. Overall, several studies adjusted for relevant covariates (e.g., age, BMI, smoking, socio-economic status), but residual or unmeasured confounding cannot be ruled out. Notably, only a minority accounted for co-exposures to other endocrine-disrupting chemicals (EDCs), which may bias the results due to mixture effects. Analytical approaches using multipollutant models or Bayesian hierarchical frameworks (e.g., Przybyla et al., 2018) represent a methodological advancement but remain underutilized. he findings synthesized in this review support growing evidence that certain organic UV filters—particularly benzophenone derivatives—are biologically active at environmental exposure levels and are associated with endocrine, reproductive, and developmental effects in humans. The consistency of hormonal alterations (e.g., thyroid hormone disruption, testosterone reduction) across diverse populations and life stages raises concern about low-dose, chronic exposure to multiple UV filters, particularly in vulnerable groups such as pregnant women, infants, and adolescents.

From a regulatory toxicology perspective, the current framework for sunscreen safety assessment remains fragmented across jurisdictions. For example, BP-3 (oxybenzone) is still widely used in the U.S. and Australia, while restrictions exist in the EU and Hawaii due to ecological concerns. However, the endocrine-disrupting potential highlighted here further supports calls for harmonized safety thresholds based not only on systemic absorption, but also on biomonitoring and real-world health outcomes.

In this context, several policy-relevant actions are warranted including: 1) reclassification of certain UV filters (e.g., BP-3, BP-2, 4-OHBP) as potential endocrine-disrupting chemicals (EDCs) under REACH (EU) and TSCA (USA) frameworks, following updated OECD criteria; 2) mandating post-marketing surveillance and biomonitoring for widely used UV filters, particularly in pregnant populations and children; 3) integration of mixture risk assessment into sunscreen ingredient approval processes, reflecting the common co-use of multiple UV filters in personal care products 3) support for green chemistry innovation, incentivizing the development and validation of safer, broad-spectrum UV filters with minimal systemic absorption and no endocrine activity; 4) public health guidance campaigns to inform consumers of appropriate sunscreen use while advocating for UV protective behaviors (e.g., shade, clothing) that reduce reliance on chemical filters.

Ultimately, the review underscores the need for a precautionary yet evidence-based regulatory approach, emphasizing human biomonitoring, developmental windows of susceptibility, and cumulative risk. Policymakers should proactively evaluate the health implications of these compounds using emerging epidemiological and mechanistic evidence rather than waiting for long-term, high-exposure effects to manifest.

Conclusions

The findings from this comprehensive review of organic UV filters, particularly benzophenones, highlight their dual significance in sunscreen formulations: their efficacy in providing photoprotection and their potential endocrine-disrupting effects. UV filters like BP-3 and BP-2 have been shown to interact with hormonal systems, with outcomes including altered testosterone levels, disrupted thyroid hormone profiles, and associations with reproductive health concerns. These findings underline the importance of considering their systemic absorption and biological effects in risk assessments.

One of the central challenges in evaluating these chemicals is the issue of mixed exposure. Studies reveal that co-exposure to multiple UV filters may produce synergistic or antagonistic effects on endocrine and reproductive health. For instance, co-exposure to BP-3, BP-1, and BP-8 has been associated with complex alterations in thyroid hormones, while mixed benzophenone exposure has demonstrated varying impacts on fertility and neonatal health outcomes. This highlights the need for more comprehensive studies designed to assess cumulative exposure effects rather than isolated compound evaluations.

Despite some consistency in findings, significant variability persists across populations, exposure scenarios, and study designs. Factors such as genetic predisposition, age, sex, and co-exposure to other environmental chemicals contribute to the heterogeneity in observed outcomes. This variability underscores the necessity for standardized methodologies and diverse, large-scale cohort studies to refine our understanding of UV filter impacts.

Environmental concerns further complicate the narrative, as UV filters persist in ecosystems, bioaccumulate, and disrupt aquatic organisms. Addressing their safety involves balancing human health considerations with their ecological implications.

In conclusion, while the use of organic UV filters remains crucial for protecting against UV radiation, their endocrine and reproductive effects warrant continued investigation. Future research should focus on:

• Mechanistic studies to elucidate biological pathways disrupted by UV filters.

• Long-term cohort studies to examine cumulative and mixed exposure outcomes.

• Development of alternatives with reduced systemic absorption and environmental persistence.

Author Contributions

M.J wrote the first draft of the manuscript with revisions and editing; K.F M.C researched the literature and contributed to the first draft. K.F reviewed the manuscript and provided support. All authors critically reviewed and made additions to subsequent drafts of the manuscript.

Funding

This research was funded by grant number 02–0108/07/780.

Data Availability

No datasets were generated or analysed during the current study.

Compliance with Ethical Standards

Competing interests

The authors declare no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.