User login
Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These . Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.
Sunscreens and benzophenones
BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.
In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.1 Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
Effects of BPs in animals
A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.1
Effects of BPs in humans and systemic absorption
In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.6
A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.7
Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.8 Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.3
However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.3,9
Risks of BPs in sunscreens and other skincare products
In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.10
In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.11
Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.3,12
Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.13 The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).13,14
Promising use of nanocapsules
The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.15
Conclusion
The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.
7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.
8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.
9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.
10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.
11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.
12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.
13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.
14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.
15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.
Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These . Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.
Sunscreens and benzophenones
BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.
In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.1 Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
Effects of BPs in animals
A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.1
Effects of BPs in humans and systemic absorption
In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.6
A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.7
Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.8 Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.3
However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.3,9
Risks of BPs in sunscreens and other skincare products
In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.10
In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.11
Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.3,12
Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.13 The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).13,14
Promising use of nanocapsules
The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.15
Conclusion
The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.
7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.
8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.
9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.
10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.
11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.
12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.
13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.
14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.
15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.
Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These . Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.
Sunscreens and benzophenones
BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.
In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.1 Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
Effects of BPs in animals
A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.1
Effects of BPs in humans and systemic absorption
In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.6
A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.7
Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.8 Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.3
However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.3,9
Risks of BPs in sunscreens and other skincare products
In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.10
In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.11
Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.3,12
Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.13 The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).13,14
Promising use of nanocapsules
The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.15
Conclusion
The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.
7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.
8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.
9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.
10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.
11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.
12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.
13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.
14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.
15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.