Benzophenone-type Ultraviolet Filters Research Articles

Concentrations, compositional profiles, and health risks of benzophenones among the Taiwanese population based on analysis of 23 daily consumed foods

In this study, we analyzed the occurrence and distribution of 11 benzophenone-type ultraviolet filters (BPs) in 893 food samples spanning 7 food categories in Taiwan. We conducted a Monte Carlo simulation to determine the carcinogenic and noncarcinogenic risks of BPs. The results indicated that cornflakes had the highest mean level of BPs (103 ng/g), followed by bread (101 ng/g) and pastries (59 ng/g). BP was the most prevalent category, followed by 4-methylbenzophenone (4-MBP), 2-hydroxybenzophenone, and benzophenone-3. Estimation of the lifetime cancer risk (LTCR) of BP (average life expectancy of 80 years) placed them in the 50th and 97.5th percentiles [P50 (P97.5)] LTCR of 1.9 × 10−7 (5.7 × 10−6), indicating that BP in food poses a low renal hazard to the Taiwanese population. The noncarcinogenic risk of BPs was evaluated using a hazard quotient and combined margin of exposure (MOET), revealing a P50 (P97.5) hazard index of < 1 for BP, 4-MBP, and methyl-2-benzoylbenzoate. Although the P50 MOET values for all age groups were within the moderate range of concern, with a more conservative extreme (P2.5), the MOET values for the 0–3, 3–6, and 6–12 age groups fell below 100, indicating a high concern for renal degeneration and hyperplasia.

Health risks posed by environmental benzophenone-type ultraviolet filters (BP-UVFs): An investigation into the binding of BP-UVFs to trypsin and their adverse effects

Benzophenone-type ultraviolet filters (BP-UVFs) are ubiquitous in the environment, and people frequently ingest them via food chain and drinking water. However, there is no clear information about whether BP-UVFs are detrimental to human health. Herein, experiments using multi-spectroscopy revealed typical BP-UVFs, i.e., benzophenone (BP), 2-hydroxybenzophenone (2-OHBP), 4-hydroxybenzophenone (4-OHBP), 2,2′-dihydroxybenzophenone (2,2′-OHBP), 2,4-dihydroxybenzophenone (2,4-OHBP), 4,4′-dihydroxybenzophenone (4,4′-OHBP), 2,4,4′-trihydroxybenzophenone (2,4,4′-OHBP), 2,2′,4,4′-tetraphydroxybenzophenone (2,2′,4,4′-OHBP), 2-hydroxy-4-methoxybenzophenone (2-OH-4-MeOBP) and 2,2′-dihydroxy-4-methoxybenzophenone (2,2′-OH-4-MeOBP), could bind to the active site of trypsin with different binding constants (2.69 × 104–1.07 × 106 L/mol), cause structural abnormalities and inhibit the enzymatic activity in varying degrees, indicating that the BP-UVFs ingestion poses a risk to human health. In contrast to previous research, this study systematically analysed the binding mechanism using an innovative combination of molecular docking and advanced quantum chemistry calculations, including molecular dynamics simulations, energy calculations, etc. The results revealed that most amino acids that make up trypsin have a greater positive electrostatic surface potential (ESP). Therefore, the greater the area and distribution of negative ESP in a particular BP-UVFs, the more easily it will bind to trypsin. This provides new insight into the binding of pollutants to proteins. This study suggests a need for better monitoring and control of environmental BP-UVFs.

A pilot study of several environmental endocrine disrupting chemicals in children with autism spectrum disorder in south China.

Autism spectrum disorders (ASD) is a group of heterogeneous neurodevelopmental disorders. Evidence has implied that environmental pollutants are important factors related to ASD. In this study, several environmental endocrine-disrupting chemicals, including parabens, benzophenone-type ultraviolet filters, hydroxyl polycyclic aromatic hydrocarbons, triclosan and tetrabromobisphenol A were analyzed in blood plasma in ASD children (n = 34) and the control children (n = 28). The results showed that parabens were the most concentrated chemicals (2.18 ng/mL, median value), followed by hydroxyl polycyclic aromatic hydrocarbons (0.73 ng/mL), benzophenone-type ultraviolet filters (0.14 ng/mL), triclosan (0.13 ng/mL) and tetrabromobisphenol A (0.03 ng/mL). ASD children accumulated significantly lower 2-hydroxy-4-methoxybenzophenone, 2,4-dihydroxybenzophenone, 4-hydroxybenzophenone and triclosan but higher 2-hydroxyphenanthrene and tetrabromobisphenol A than the control children (0.02/0.09 ng/mL of 2-hydroxy-4-methoxybenzophenone, p < 0.05; 0.04/0.07 ng/mL of 2,4-dihydroxybenzophenone, p < 0.05; 0.03/0.04 ng/mL of 4-hydroxybenzophenone, p < 0.05; 0.13/1.22 ng/mL of triclosan, p < 0.01; 0.03 ng/mL/not detected of 2-hydroxyphenanthrene, p < 0.05; 0.03/0.004 ng/mL of tetrabromobisphenol A, p < 0.05). Gender differences in certain environmental endocrine-disrupting chemicals were evident, and the differences were more inclined toward boys. Positive associations between 2-hydroxy-4-methoxybenzophenone and triclosan, and tetrabromobisphenol A and 2-hydroxyphenanthrene were found in ASD boys. Binary logistic regression analysis showed that the adjusted odds ratio value of 2-hydroxyphenanthrene in ASD boys was 11.0 (1.45-84.0, p < 0.05). This is the first pilot study on multiple environmental endocrine-disrupting chemicals in children with ASD in China.

Distribution of phthalate metabolites, benzophenone-type ultraviolet filters, parabens, triclosan and triclocarban in paired human hair, nail and urine samples

In this study, the distribution of nineteen ingredients of personal care product (PCPs), including seven metabolites of phthalates (mPAEs), five benzophenone-type ultraviolet filters (BPs), and seven antimicrobial agents (AAs), were investigated in paired human hair, nail and urine samples. The median concentrations of ΣmPAEs, ΣBPs and ΣAAs were 135, 2.76 and 179 ng/g in hair, 37.3, 2.95 and 297 ng/g in nails, and 345, 4.03 and 50.1 ng/mL in urine, respectively. Mono-methyl phthalate (49%), 2,4-dihydroxybenzophenone (45%) and triclosan (71%) were the most abundant mPAE, BP and AA in hair samples, respectively, and had similar abundance in nail samples. In contrast, mono-n-butyl phthalate (45%), 4-hydroxy benzophenone (29%) and methyl paraben (54%) were the predominant mPAE, BP and AA in urine samples, respectively. Significant differences in the concentrations of some target compounds were observed between male and female but inconsistent across different matrices. Moreover, most compounds with significant correlations had quite different correlation coefficients in each matrix. No significant correlations were found between hair, nail and urine samples for most of the target analytes. These results suggest these analytes have matrix-specific distribution, and it is necessary to use multiple matrices to comprehensively assess the risk of ingredients of PCPs to human health.

Benzophenone-type ultraviolet filters inhibit human and rat placental 3β-hydroxysteroid dehydrogenases: Structure-activity relationship and in silico docking analysis

Benzophenones (BPs) are a class of chemicals found in various personal care and cosmetic products, such as sunscreens and lotions. Their usage is known to cause reproductive and hormonal health risks, but the exact mechanism of action remains unknown. In this study, we investigated the effects of BPs on human and rat placental 3β-hydroxysteroid dehydrogenases (3β-HSDs), which play a crucial role in the biosynthesis of steroid hormones, particularly progesterone. We tested inhibitory effects of 12 BPs, and performed structure-activity relationship (SAR) and in silico docking analysis. The potency of BPs to inhibit human 3β-HSD1 (h3β-HSD1) is BP-1 (IC50, 8.37 μM)>BP-2 (9.06 μM)>BP-12 (94.24 μM)>BP-7 (1160 μM) >BP-8 (1257 μM) >BP-6 (1410 μM) > other BPs (ineffective at 100 μM). The potency of BPs on rat r3β-HSD4 is BP-1 (IC50, 4.31 μM)>BP-2 (117.3 μM)>BP-6 (669 μM) >BP-3 (820 μM)>other BPs (ineffective at 100 μM). BP-1, BP-2, and BP-12 are mixed h3β-HSD1 inhibitors and BP-1 is a mixed r3β-HSD4 inhibitor. LogP, lowest binding energy, and molecular weight were positively associated with IC50 for h3β-HSD1, while LogS was negatively associated with IC50. The 4-OH substitution in the benzene ring plays a key role in enhancing the effectiveness of inhibiting h3β-HSD1 and r3β-HSD4, possibly through increasing water solubility and decreasing lipophilicity by forming hydrogen bonds. BP-1 and BP-2 inhibited progesterone production in human JAr cells. Docking analysis shows that 2-OH of BP-1 forms hydrogen bonds with catalytic residue Ser125 of h3β-HSD1 and Thr125 of r3β-HSD4. In conclusion, this study demonstrates that BP-1 and BP-2 are moderate inhibitors of h3β-HSD1 and BP-1 is a moderate inhibitor of r3β-HSD4. There is a significant SAR differences for 3β-HSD homologues between BPs and distinct species-dependent inhibition of placental 3β-HSDs.

Safety of benzophenone-type UV filters: A mini review focusing on carcinogenicity, reproductive and developmental toxicity

Consumer products containing benzophenone-type ultraviolet (UV) filters (BPs) have been widely accepted by the public, resulting in the widely existence of various BPs in the human body and environment. In recent years, more and more evidences show that BPs are endocrine disruptors. In view of the continuous exposure risk of BPs and their endocrine disrupting characteristics, the carcinogenicity of BPs and their effects on reproduction and development are of particular concern. However, due to the wide varieties of BPs and the scattered toxicity studies on BPs, people have a limited understanding on the safety of BPs. Therefore, this paper systematically reviews the carcinogenicity, reproductive and developmental toxicity of BPs in order to expand people's knowledge on the health risks of BPs and screen for more safe BPs. Although existing toxicological studies are insufficient, it can be determined that BPs have different potentials for carcinogenicity, and reproductive and developmental toxicity. Among those BPs, 2-hydroxyl-4-methoxyl benzophenone needs to be used with caution due to its adverse effects on cancer cell proliferation and migration, reproductive ability, sex differentiation, neurodevelopment, and so on. It is worth noting that functional group substitutions significantly affect the interaction between BPs and biomolecules such as DNA, cancer cells, and seminal fluid, resulting in different levels of toxicity. In short, it is very necessary to evaluate the carcinogenicity, reproductive and developmental toxicity of BPs, which is of great significance for establishing reasonable BPs content standards in cosmetics, water quality treatment standards for BPs, and so on.

Mechanochemically synthesized zeolitic imidazolate framework-8 as sorbent for dispersive solid-phase extraction of benzophenone-type ultraviolet filters in aqueous samples

Benzophenone-type ultraviolet filters (BP-UVFs) are a group of emerging contaminants, which found in various environmental aqueous samples raising potential risks for public health concern and could bioaccumulate in the food chain. This study describes a simple and “green” method to rapidly analyze five BP-UVFs that are frequently found in surface water and in seawater samples. Dispersive solid-phase extraction (DSPE) using a zeolitic imidazolate framework‑8 (ZIF-8) as the sorbent was applied to efficiently extract the BP-UVFs from aqueous samples, and they were then detected and quantified by UHPLC-electrospray ionization (+)-quadrupole time-of-flight mass spectrometry (UHPLC-ESI (+)-QTOF-MS). The ZIF-8 sorbent was synthesized by a green one-step mechanochemical process using water-assisted grinding and a stoichiometric reaction. The Box-Behnken Design coupled with the response surface method was applied to optimize the main DSPE extraction factors. The developed method was fully validated, showing low limits of quantification (LOQs; 0.3−20 ng L−1), satisfactory mean spiked recoveries (72−105%), and a high level of precision (3−9%). A preliminary analysis of the surface water and seawater samples revealed that 2-hydroxy-4-methoxybenzophenone (BP-3) was the most common BP-UVF present in our aquatic environment, likely due to its widespread applications and slow rate of degradation.

Benzophenone-1 induced aberrant proliferation and metastasis of ovarian cancer cells via activated ERα and Wnt/β-catenin signaling pathways

Benzophenone-1 (BP-1) belongs to personal care product-related contaminants of emerging concern and has been recently reported to induce xenoestrogenic effects. However, the underlying mechanisms leading to the activation of target receptors and subsequent various adverse outcomes remain unclear, which is beneficial to safety and health risk assessment of benzophenone-type ultraviolet filters with their widespread occurrence. Herein, we investigated disrupting effects of BP-1 at environmentally relevant concentrations (10−9–10−6 M) on estrogen receptor (ER) α-associated signaling pathways. Molecular dynamics simulations together with yeast-based assays revealed the steady binding of BP-1 to ERα ligand binding domain (LBD) and hence the observed agonistic activity. BP-1 triggered interaction between ERα and β-catenin in human SKOV3 ovarian cancer cells and caused translocation of β-catenin from the cytoplasm to the nucleus, leading to aberrant activation of Wnt/β-catenin. BP-1 consequently induced dissemination of SKOV3 via regulating epithelial-mesenchymal transitions (EMT) biomarkers including minimally downregulating ZO-1 gene to 78.0 ± 10.1% and maximally upregulating MMP9 gene to 144.1 ± 29.7% and promoted 1.03–1.83 fold proliferation, migration and invasion of SKOV3. We provide the first evidence that the BP-1 activated ERα triggers crosstalk between ERα and Wnt/β-catenin pathway, leading to the abnormal stimulation and progression of SKOV3 cancer cells.

Concentrations of bisphenols, benzophenone-type ultraviolet filters, triclosan, and triclocarban in the paired urine and blood samples from young adults: Partitioning between urine and blood

Bisphenols (BPs), benzophenone-type UV filters (BP-type UV filters), triclosan (TCS), and triclocarban (TCC) are endocrine-disrupting chemicals (EDCs) and commonly used in consumer and personal care products. In the present study, seven BPs, eight BP-type UV filters, TCS, and TCC were quantified in 196 paired urine and blood samples collected from young adults in South China. Benzophenone-7 and benzophenone-9 were not detected in all samples, while other target compounds were widely detected in 39%–96% of the urine and 14%–96% of the blood samples, and the median concentrations ranged from <0.02 (specific gravity adjusted: < 0.02) to 2.33 (2.05) ng/mL and <0.01–2.66 ng/mL in the urine and blood samples, respectively. Females had higher levels of most target analytes, and gender-related differences (p < 0.05) were found in the blood levels of benzophenone-2 (females vs. males: 0.84 vs. <0.01 ng/mL), ΣBP (sum of BP-type UV filters; 1.61 vs. 0.98 ng/mL), TCS (3.89 vs. 1.69 ng/mL), and ΣTC (sum of TCS and TCC; 5.77 vs. 3.02 ng/mL). We calculated the portioning of the target compounds between blood and urine (B/U ratios). The B/U ratios of bisphenol F, benzophenone-2, benzophenone-6, 4-hydroxy benzophenone, TCS, and TCC were higher than 1, showing that these analytes have higher enrichment capacities in human blood. To the best of our knowledge, this is the first study to simultaneously analyze the concentrations of BPs, BP-type UV filters, TCS, and TCC in the paired urine and blood samples of young adults in South China.

Profiles of parabens, benzophenone-type ultraviolet filters, triclosan, and triclocarban in paired urine and indoor dust samples from Chinese university students: Implications for human exposure

Parabens, benzophenone (BP)-type UV filters, triclosan (TCS), and triclocarban (TCC) are commonly used in personal care products. Human exposure to these compounds has received increasing concern because of their adverse health effects. However, the levels of these chemicals in paired urine and indoor samples have never been simultaneously measured. In this work, eight parabens, eight BP-type UV filters, TCS, and TCC were measured in paired urine and indoor dust samples collected from university students and their dormitories in South China. The target analytes were commonly measured in urine (71%–100%) and indoor dust (30%–98%), with median concentrations ranging from 0.16 ng/mL to 19.3 ng/mL in urine and from <0.01 ng/g to 3700 ng/g in indoor dust samples. Females had high levels of most of these target compounds, and gender-related differences were found in the levels of most target analytes. Positive correlations were found in the levels of methylparaben, ethyl paraben, benzophenone-3, and TCS between urine and indoor dust samples. This finding suggested that indoor dust is an important source for human exposure to these compounds. The estimated daily intake (EDI) of these analytes in paired samples was also evaluated. The median EDI-urine values of target analytes varied in the range of 4.02–59,280 ng/kg bw/day. Females had higher median EDI-urine values for most of target analytes than males. In addition, the median EDI-indoor dust values of most target analytes in dust from female dormitories were higher than those in dust from male dormitories. Indoor dust ingestion only had minor contribution (<0.5%) to the total exposure. To the best of the authors' knowledge, this study is the first to simultaneously analyze the concentrations of parabens, BP-type UV filters, TCS, and TCC in the paired urine and indoor samples from university students in South China.

Simultaneous trace analysis of 10 benzophenone-type ultraviolet filters in fish through liquid chromatography–tandem mass spectrometry

We developed and validated a trace analytical method for the simultaneous determination of 10 benzophenone (BP)-type ultraviolet filters (BPs; BP, BP-1, BP-2, BP-3, BP-8, 2-hydroxybenzophenone [2-OHBP], 4-hydroxybenzophenone [4-OHBP], 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate [M2BB], and 4-benzoylbiphenyl [PBZ]) to analyze BPs in 110 commercial fish samples. The quick, easy, cheap, effective, rugged, and safe (QuEChERS) technique coupled with ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) was employed. The developed method exhibited satisfactory linearity (R2 > 0.993), favorable precision with intraday and interday relative standard deviation ranges of 1.0%–26.6% and 2.3%–29.3%, respectively, and a limit of detection ranging from 0.001 to 0.1 ng/g. BP and 2-OHBP were detected in 100% of the samples; BP-3, 4-OHBP, PBZ, and 4-MBP were detected in >70% of the samples; M2BB was detected in 33% of the samples, and BP-2 and BP-8 were not detected. Higher mean (minimum–maximum) levels of 2-OHBP and BP were found in fish samples with low lipid content, ranging from 18 (1.1–218.3) to 10 (0.5–45.4) ng/g, and those with high lipid content, ranging from 22 (1.5–76.4) to 9.6 (5.2–18.5) ng/g; low levels of the remaining six BPs were found, ranging from 0.01 to 0.9 ng/g. The mean 2-OHBP levels were 21.3, 14.4, and 30.2 ng/g for fish samples obtained from aquaculture in Taiwan, the wild in Taiwan, and different countries, respectively, with levels up to 218.3 ng/g (field eel) for a sample from Indonesia. BPs may not pose a health risk to Taiwanese adults through the consumption of fish; however, additional studies are needed to examine the risk that these contaminants may pose to ecosystems and human health.

Occurrence and transfer of benzophenone-type ultraviolet filters from the pregnant women to fetuses

Benzophenone (BP)-type ultraviolet (UV) filters are widely used in personal care products. Some of them have been identified as endocrine disrupting chemicals. However, little is known about the occurrence of BP-type UV filters in paired maternal-fetal samples. In this study, we investigated the occurrence of eight BP-type UV filters in paired maternal-fetal samples collected from Southern China. Among target analytes, only benzophenone-3 (BP-3) was frequently (detection rate > 80%) detected in maternal-fetal samples, i.e., maternal serum (MS), cord serum (CS), maternal urine (MU) and amniotic fluid (AF). BP-3 was the dominant compound in MS (median: 0.14 ng/mL), CS (0.16) and AF (0.12); whereas MU was dominated by benzophenone-1 (BP-1, 2.85). The median CS/MS ratios (i.e., placental transfer rates) of 4-hydroxy benzophenone (4-OH-BP, 2.35), BP-1 (1.52), benzophenone-4 (BP-4, 1.06), and BP-3 (1.03) were higher than 1.0, suggesting that exposure levels of these chemicals in fetuses were greater than those in mothers. Significant positive correlations (r = 0.667, p < 0.001) of BP-3 concentrations were found between MS and CS, which suggested that MS could be an indicator of fetal exposure to BP-3. Furthermore, the CS/MS ratios of 4-OH-BP, BP-1, BP-3, and benzophenone-8 (BP-8) increased with decreasing molecular weight or log Kow. Passive diffusion may play an important role in placental transfer of these BP type UV filters. The MU/MSBP-3 ratio (5.86) was relatively higher than that of MU/MSBP-1 (0.89), which indicated that BP-3 excretes rapidly in urine. The present study documents the occurrence of eight BP-type UV filters in matched MS, CS, MU and AF samples for the first time in China.

Antioxidant responses in cyanobacterium Microcystis aeruginosa caused by two commonly used UV filters, benzophenone-1 and benzophenone-3, at environmentally relevant concentrations

Benzophenone-type ultraviolet filters (BPs) have recently been recognized as emerging organic contaminants. In the present study, the cyanobacterium Microcystis aeruginosa was exposed to environmentally relevant levels (0.01-1000 μg L-1) of benzophenone-1 (BP-1) and benzophenone-3 (BP-3) for seven days. A battery of tested endpoints associated with photosynthetic pigments and oxidative stress was employed for a better understanding of the mode of action. The tested cyanobacterium could uptake the two BPs (27.4-54.9%) from culture media. The two BPs were able to inhibit the production of chlorophyll a (chl-a) and promote the accumulation of carotenoids, leading to unaffected chl-a autofluorescence. Slightly increased malondialdehyde (MDA) contents suggested that BP-1 and BP-3 caused moderate oxidative stress. BP-1 stimulated the activities of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione S-transferase (GST) in M. aeruginosa while BP-3 increased the activities of SOD, GST, and glutathione (GSH), showing a concentration- and time-dependent relationship. The activities of other biomarkers, such as catalase (CAT) and glutathione peroxidase (GPx) fluctuated depending on exposure time and concentration. The overall results suggested that the two BPs can trigger moderate oxidative stress in M. aeruginosa and the tested cyanobacterium was capable of alleviating stress by different mechanisms.

Sensitive detection of benzophenone-type ultraviolet filters in plastic food packaging materials by sheathless capillary electrophoresis–electrospray ionization–tandem mass spectrometry

While they are commonly used as ultraviolet (UV) filters in plastic food packaging materials, benzophenones (BPs) are reported as environmental endocrine disruptors, and some of them possess significant estrogenic activity. Therefore sensitive determination of the content of those UV filters in plastic polymers is of vital importance in safety assessment of food packaging materials. Here, the sheathless capillary electrophoresis–electrospray ionization–tandem mass spectrometry (CE–ESI–MS/MS) method is applied for the first time to sensitively detect BP-type UV filters in plastic food packaging materials. We investigate and optimize a variety of factors that may affect ESI–MS efficiency and CE separation. Sensitive detection of six BP-type UV filters is achieved using sheathless CE–ESI–MS/MS in conjunction with accelerated solvent extraction and solid phase extraction, with the limit-of-detection of 7 pg/mL–2.4 ng/mL. The method exhibits excellent inter/intra-day repeatability along with the advantages of efficient separation, rapid analysis, low sample consumption and high sensitivity. Six BP-type UV filters in eight different brands of plastic films obtained from supermarkets are successfully analyzed using the method. Good recoveries of 81.3–104.1% at three levels of spiked concentrations are achieved with low RSDs (n = 5) of 2.5–8.7%. Our study shows that the sheathless CE–ESI–MS/MS is a robust and reliable method for sensitive and rapid analysis of UV filters, which would be of potential application in safety assessment of plastic food packaging materials.

Occurrence and fate of benzophenone-type UV filters in aquatic environments: a review

Benzophenone-type ultraviolet filters (BP-type UV filters or BPs) are extensively used in a diverse array of personal care products (PCPs), including sunscreens and many cosmetics.

Comparative toxicity related to metabolisms of benzophenone-type UV filters, potentially harmful to the environment and humans

Recently, sunscreens containing ultraviolet (UV)-blocking substance actively encourage to reduce damage caused by solar UV radiation. Benzophenone (BP)-type UV filters have become widely used as UV stabilizers in skin-moisturizing products and sunscreen lotions of human skin and hair. However, very little information is available regarding the potential harmful effects of long term exposure to these substances. Therefore, we investigated the possibility of genotoxic effects related to metabolism of BP-type UV filters in mouse lymphoma L5178Y cells. In metabolism process of BP-type UV filters, BP was mainly converted to benzhydrol (BH) and 4-hydroxybenzophenone (HBP) (i.e., type A UV filters). In contrast, HMB was converted into at least three intermediates, including 2,4-dihydroxybenzophenone (DHB), which was formed via o-demethylation and subsequently converted into 2,3,4-trihydroxybenzophenone (THB), and 2,2′-dihydroxy-4-methoxybenzophenone (DHMB), which formed via the aromatic hydroxylation of HMB (i.e., type B UV filters). The comet assay was used to assess DNA damage in type A and B UV filters-treated cells. We found that cells exposed to type A or B UV filters showed significant DNA damage compared to untreated cells. Exposure to HBP, the hydroxylated metabolite of BP, and DHB and THB, the di- and tri-hydroxylated metabolites of HMB, resulted in particularly severe DNA damage (P<0.05). Therefore, we suggest that BP-type UV filters with a hydroxyl group at the para-position (e.g., HBP, DHB, and THB) may induce single-stranded DNA breakage in L5178Y cells.

Transformation of benzophenone-type UV filters by chlorine: Kinetics, products identification and toxicity assessments

The present study focused on the kinetics, transformation pathways and toxicity of several benzophenone-type ultraviolet filters (BPs) during the water chlorination disinfection process. The transformation kinetics of the studied three BPs was found to be second-order reaction, which was dependent on the concentration of BPs and chlorine. The second-order rate constants increased from 86.7 to 975M−1s−1 for oxybenzone, 49.6–261.7M−1s−1 for 4-hydroxybenzophenone and 51.7–540M−1s−1 for 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid with the increasing pH value from 6 to 8 of the chlorination disinfection condition. Then the transformation products (TPs) of these BPs were identified by HPLC-QTof analysis. Several transformation pathways, including electrophilic substitution, methoxyl substitution, ketone groups oxidation, hydrolysis, decarboxylation and ring cleavage reaction, were speculated to participate in the chlorination transformation process. Finally, according to the toxicity experiment on luminescent bacteria, Photobacterium phosphoreum, enhanced toxicity was observed for almost all the TPs of the studied BPs except for 2,2′-dihydroxy-4,4′-dimethoxybenzophenone; it suggested the formation of TPs with more toxic than the parent compounds during the chlorination process. The present study provided a foundation to understand the transformation of BPs during chlorination disinfection process, and was of great significance to the drinking water safety.

Couples' urinary concentrations of benzophenone-type ultraviolet filters and the secondary sex ratio

The secondary sex ratio (SSR), defined as the ratio of males to females at birth, has been investigated in relation to endocrine disruptors to search for environmental toxicants perturbing human sex selection. Benzophenone (BP)-type ultraviolet (UV) filters, which are used in sunscreens and personal care products, have been reported to exert estrogenic and anti-androgenic activities. This study aimed to evaluate the association between maternal, paternal, and couple urinary concentrations of BP-type UV filters and the SSR, given the absence of previous investigation. The study cohort comprised 220 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and who had a singleton birth during the follow-up period. Couples' urinary concentrations of five BP-type UV filters (ng/mL) were measured using triple-quadrupole tandem mass spectrometry: 2,4-dihydroxybenzophenone (BP-1), 2,2′,4,4′-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2′-dihydroxy-4-methoxybenzophenone (BP-8), and 4-hydroxybenzophenone (4-OH-BP). Modified Poisson regression models were used to estimate the relative risks (RRs) of a male birth for each BP-type UV filter, after adjusting for potential confounders. When maternal and paternal urinary BP-type UV filter concentrations were modeled jointly, both maternal BP-2 (2nd vs 1st tertile, RR, 0.62, 95% confidence interval [CI], 0.43–0.91) and paternal BP-2 (3rd vs 1st tertile, RR, 0.67, 95% CI, 0.45–0.99; p-trend, 0.04) were significantly associated with an excess of female births. Contrarily, maternal 4-OH-BP was significantly associated with an excess of male births (2nd vs 1st tertile, RR, 1.87, 95% CI, 1.27–2.74; 3rd vs 1st tertile, RR, 1.80, 95% CI, 1.13–2.87; p-trend, 0.02). Our findings provide the first evidence suggesting that BP-type UV filters may affect the SSR. However, future corroboration is needed, given the exploratory design of this study.

Bisphenol A, benzophenone-type ultraviolet filters, and phthalates in relation to uterine leiomyoma

Bisphenol A, benzophenone-type UV filters, and phthalates are chemicals in high production and use including in a range of personal care products. Exposure of humans to these chemicals has been shown to affect endocrine function. Although short-lived, widespread exposure may lead to continual opportunity for these chemicals to elicit health effects in humans. The association of these chemicals with incident uterine leiomyoma, an estrogen sensitive disease, is not known. Urinary concentrations of bisphenol A (BPA), five benzophenone-type UV filters (2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2׳-dihydroxybenzophenone (2,2׳OH-4MeO-BP), 2,2׳4,4׳-tetrahydroxybenzophenone (2,2׳4,4׳OH-BP), and 4-hydroxybenzophenone (4OH-BP), and 14 phthalate monoesters were quantified in 495 women who later underwent laparoscopy/laparotomy at 14 clinical sites for the diagnosis of fibroids. Significantly higher geometric mean creatinine-corrected concentrations of BPA, 2,4OH-BP, and 2OH-4MeO-BP were observed in women with than without fibroids [BPA: 2.09µg/g vs. 1.46µg/g p=0.004; 2,4OH-BP:11.10µg/g vs. 6.71µg/g p=0.01; 2OH-4MeO-BP: 11.31µg/g vs. 6.10µg/g p=0.01]. Mono-methyl phthalate levels were significantly lower in women with than without fibroids (1.78µg/g vs. 2.40µg/g). However, none of the exposures were associated with a significant odds ratio even when adjusting for relevant covariates. There was a lack of an association between select nonpersistent chemicals and the odds of a fibroid diagnosis.

Urinary concentrations of benzophenone-type UV filters and semen quality

Benzophenone-type ultra violet (UV) filters are highly effective chemicals added to sunscreen and personal care products for the protection of skin and hair against harmful UV rays. Despite evidence suggesting estrogenic and anti-androgenic in vivo and in vitro activity, no human studies have assessed reproductive outcomes or semen quality, specifically.