Benzophenones

UV filters, including benzophenones, are widely used in cosmetics, personal care products, food contact materials, inks, textiles and other consumer products. Therefore, there is a high potential for the general public (including vulnerable populations) to be exposed to benzophenones.

While UV filters in sunscreens and cosmetics have been effective in protecting against a variety of UV-related pathologies, such as sunburns and melanomas, growing popularity of sunscreens and increasing potential exposure has led to increased societal concern about their potential impact on the environment and human health.

Benzophenone 3 (BP-3) displays a low acute toxicity profile. It is not considered as being irritating to the skin and the eyes¹. Results from animal studies—primarily dietary studies that affected body weight gain—showed alterations in liver, kidney, and reproductive organs in rats and mice with BP-3 administered dermally and orally². BP-3 is on the Community Rolling Action Plan (CoRAP) list because of potential endocrine disruption³. BP-3 elicited anti-androgenic activity in a human breast carcinoma cell line⁴ and interferes with functions of human sperm cells in vitro⁵. Critical effects are maternal and developmental toxicity⁶. In female mice, low dose exposure causes long-lasting alterations to mammary gland morphology and function⁷. Studies in rat primary cortical neuronal cultures and neuroblastoma cell lines showed decreased cell viability after BP-3 treatment at moderate concentrations⁸.

In a study on young men from Spain, there was a significant positive association between urinary BP-3 concentrations and serum FSH levels⁹. In male adolescents in the US, urinary BP-3 was associated with lower total testosterone¹⁰. In a study of young Danish men, associations between male reproductive health parameters and urinary levels of benzophenones such as BP-3, BP-1 and 4-HBP were observed in filaggrin gene mutation carriers but not in controls¹¹. In a study in healthy, premenopausal women, UV filter factors (BP-1, BP-3) were associated with decreased estradiol, FSH, and LH¹².

Benzophenone is possibly carcinogenic to humans (Group 2B, IARC classification, based on sufficient evidence in experimental animals).⁴ Benzophenone exerts tumourigenic effects in rats and mice in the liver, the kidney and in the haematopoetic system, including rare histiocytic sarcomas. Available evidence supports that benzophenone is not genotoxic. Benzophenone meets the criteria for classification as carcinogenic in category 2¹³. Benzophenone may alter endocrine signalling through multiple effects on receptors.⁴ Critical effects are liver and kidney effects.⁶

Benzophenone-1 (BP-1) is used as a UV filter, but is also the major metabolite of BP-3. BP-1 is not irritating nor sensitizing at concentrations that may be found in cosmetic products. The toxicity studies available indicate low acute and subchronic toxicity of BP-1. BP-1 is not mutagenic. The lowest effect levels were determined for reproductive toxicity with lowest observable adverse effect levels (LOAELs) between 100-625 mg/kg and NOAELs between 100-250 mg/kg. BP-1 is on the European Commission priority list of potential endocrine disruptors.⁶

In a study of young Danish men, associations between male reproductive health parameters and urinary levels of benzophenones such as BP-3, BP-1 and 4-HBP were observed in filaggrin gene mutation carriers but not in controls.¹¹ In a study in healthy, premenopausal women, UV filter factors (BP-1, BP-3) were associated with decreased estradiol, FSH, and LH.¹²

Benzophenone-2 (BP-2) is a UV filter used in personal care products. BP-2 may disturb thyroid hormone homeostasis by inhibiting or inactivating thyroid peroxidase, effects that are even more pronounced in the absence of iodide¹⁴. Both BP-2 and BP-3 were shown to exert uterotrophic effects and BP2 was shown to bind to estrogen receptors¹⁵. In fish and mammals, BP-2 induces a variety of reproductive disorders, including feminization of male fish, inhibition of gamete development in fish, reduction of testosterone secretions from testicular tissue, induction of uterotrophic effects in rats, changes in bone density and osteo-regulation, changes in LH, cholesterol levels, fat deposition, and an increased risk of endometriosis¹⁶.

In a study on exposure to UV filters and fertility, male partners’ concentrations BP-2 was associated with reduced fecundity¹⁷.

4-Methylbenzylidene camphor (4-MBC) is found in cosmetics and in drinking water.⁶ The available data suggest no genotoxicity, mutagenic potential or phototoxicity of 4-MBC. However, this chemical is suspected to have a mild endocrine disrupting effect on the thyroid gland. Experiments on rats found 4-MBC to have development toxicity.^6,18

3-benzylidene camphor (3-BC) – 3-BC is a potential endocrine disrupter. Experiments in vivo and in vitro revealed oestrogenic activity. In addition, 3-BC was found to interrupt sexual development and maturation in animal models.¹⁴ According to the Scientific Committee on Consumer Safety, hormonal activities of 3-BC have been reported in vitro: estrogenic and anti-estrogenic effects as well anti- androgenic activities. In vivo, the expression of target genes (ERα, ERβ, SRC-1 and PR (progesterone receptor)) has been shown to be altered in both males and females rats.¹⁵

4-hydroxy benzophenone (4-HBP) is used as an industrial UV-filter. 4-HBP has potential to disrupt endocrine activity, and fetal growth. 4-HBP exposure in women carrying a male fetus was associated with increased maternal thyroid hormone concentrations, in addition to decreased birth outcomes (lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group)¹⁹.

4-methylbenzophenone (4-MBP) is used in paints and varnishes, in food packaging but not in cosmetics.⁵ According to an assessment by EFSA, the currently available data on 4-methylbenzophenone are insufficient to enable the assessment of this substance with respect to its human toxicological effects. 4-MBP is expected to be a non-genotoxic carcinogen²⁰.

Please see the link to the scoping document on Benzophenones at the top of the page for this information.

• Benzophenone is manufactured and/or imported in the European Economic Area in 1000-10000 tonnes per year; it is used by consumers, by professional workers (widespread uses), in formulations or re-packaging and at industrial sites.
• Benzophenones are used in cosmetics and in personal care products, food contact materials, coating products, fillers, modelling clay and finger paints. UV-absorbers and UV filters including benzophenone-1 and benzophenone-3 are added to food packaging to protect the packaging itself and the contained food from harmful UV light.⁶
• Release to the environment is likely to occur from: industrial use, indoor use (e.g. machine wash detergents, personal care products, paints and coating, fragrances and air fresheners).
• Biological half-life (in serum) of 19 hours ⁴.
• Human biomonitoring (HBM) data: pregnant women in US (California)²¹, France²², China²³, Israel²⁴, general public in Belgium²⁵, Denmark²⁶, and the US²⁷. Data on exposure in children in available for the US²⁸, Denmark^29,30,31,32, China³³, Australia³⁴, Taiwan³⁵ and Germany³⁶ (GerES V, publication in preparation, for HBM4EU available data on 3 to 14 year old children and adolescents; young adults: 20-29 years, Environmental Specimen Bank).
• Several biomonitoring studies (including NHANES) have focused on BP-3.²⁷ BP-3 has been widely detected in several biomonitoring studies with urinary levels correlated with the use of personal care products. Higher BP3 exposure has been observed in the female population, possible due to its presence in personal care products²⁷.

• BP-3 can be directly measured and quantified in urine in HBM studies. Benzophenones including BP-1 and BP-3 can be measured using an on-line LC/LC-MS/MS method for the simultaneous determination of nine parabens and seven environmental phenols in urine⁴¹. In addition, three oxidative metabolites (2,4-dihydroxylbenzophenone, 2,2′-dihydroxy-4-methoxybenzophenone, and 2,3,4-trihydroxybenzophenone) can also be measured in HBM studies using quantitative analytical methods⁴².
• 4 – MBC urinary metabolites (3- (4-carboxybenzylidene) camphor and 3-(4-carboxybenzylidene)-6-hydroxycamphor) can be measured using gas chromatography high resolution mass spectrometry (GC-HRMS)⁴³.
• LC-MS/MS based methods have been developed in Germany³⁶ for simultaneous biomonitoring of nine parabens and seven environmental phenols including BP-3 and BP-1 and in Denmark³² for simultaneous biomonitoring of nine UV filters in urine (BP, BP-1, BP-2, BP-3, 3-BC, 4-MBC, 4-HBP, 4-HBP, and 5-chloro-2- hydroxybenzophenone). However, urine might not be the preferred matrix for measurements of the most lipophilic UV filters such as 3-BC and 4-MBC.

Following on the Advisory Board’s advice to strengthen the science-policy interface, HBM4EU developed a strategic and systematic approach to outreach and align science and policy. A legislative mapping exercise was done by RPA Consultants, providing relevant public policy processes that may benefit from the knowledge generated under HBM4EU. The documents are available for consultation here, with the tables presented here.

Since September 2017 the use of BP-3 in the EU is restricted to 6% in cosmetic sunscreen products and up to 0.5 % in other cosmetic products³⁷. According to the Cosmetics Regulation (EU Regulation 1223/2009). BP-4 and BP-5 are permitted as UV filters in cosmetic products. 4-MBC is allowed as a UV filter in cosmetic products with a maximum concentration of 4% in ready-for-use preparations³⁸.

According to the Scientific Committee on Consumer Safety, the use of 3-BC as a UV-filter in cosmetic products in a concentration up 2.0% is not safe³⁹.

Benzophenone is approved as an additive in plastic food contact materials, with a specific migration limit of 0.6 mg/kg⁴⁰.

Inks are not covered by a specific European legislation on food contact materials. The use of printing inks has to comply with the general rules of Regulation (EC) No 1935/2004 and with good manufacturing practice as laid down in Commission Regulation (EC) No 2023/2006.

1. Are sensitive, reliable and cost effective methods and biomarkers available to measure UV filters?
2. What are current exposure levels to benzophenones in the EU population (cumulative exposure from different exposures sources)?
3. What are the major sources of exposure to benzophenones in the EU population and in vulnerable groups such as children and pregnant women? (Sunscreens, cosmetics and personal care products, plastic and other food contact materials, textiles, furnitures and building materials and others)
4. Do exposure levels differ significantly between different EU countries (possibly related to climate)?
5. Do exposure levels differ between different sub-groups: elderly, adults, and children? between males and females? Between adults of different age groups? Between individuals in different ethnic subgroups (perhaps due to differences in use of sunscreen products)?
6. Are current exposure levels safe in relation to the endocrine and carcinogenic properties of benzophenones? (for the general population and for vulnerable groups such as children and pregnant women)
7. Was the restriction of BP-3 in cosmetics in the EU (September 2017) effective in reducing public exposure? Did exposure to other benzophenone or other UV filter compounds increase as a result?

Please find answers to the updated (2020) Policy-related questions on Benzophenones here 

In the interest of transparency and accountability, HBM4EU invites interested stakeholders to submit comments on the scoping document on acrylamide.

All submitted comments will be made available for download on this webpage and will be taken into consideration by the HBM4EU consortium, where possible.

Please click here to submit your comments.

Please click here to access the Substance Report.

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