CAS: Towards sustainable sunscreens: identifying chemical structures in sunscreens linked to phototoxicity in corals

CAS：迈向可持续防晒霜：确定防晒霜中与珊瑚光毒性相关的化学结构

• 批准号: 2114790
• 负责人: William Mitch
• 金额: $ 45万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2114790&HistoricalAwards=false
• 关键词: CAS; Towards; sustainable; sunscreens; identifying

A large fraction of the world's coral reefs are at a high risk of extinction. Although much of the threat is due to global factors, coral declines can also be significantly exacerbated by local factors. Recent concern has focused on oxybenzone, a common sunscreen component, due to observations that oxybenzone is toxic to adult corals and reduces survival of juvenile coral. The reasons for this toxicity are unclear, and improved understanding is needed to enable the design of sustainable sunscreens that are truly safe for coral reefs. This research project will characterize the chemical structures within organic sunscreen components or their metabolites that are responsible for phototoxicity to corals, focusing on five of the most common organic sunscreen components: oxybenzone, homosalate, octisalate, octinoxate, and octocrylene. This improved understanding will lay the groundwork for the design of new and sustainable sunscreen components that do not exhibit phototoxicity. The central hypothesis is that the presence or absence of a hydroxyl group adjacent to the aromatic carbonyl (present in each of the five compounds) is a critical determinant of whether a sunscreen component is phototoxic. Sunlight absorption forms excited triplet states of aromatic carbonyls that can generate Reactive Oxygen Species (ROS), resulting in phototoxicity. However, the hydroxyl group adjacent to the aromatic carbonyl in oxybenzone, homosalate, and octisalate inhibits ROS production during sunlight illumination by quenching excited-state triplets. The hypothesis, backed by preliminary evidence, is that oxybenzone, homosalate, and octisalate themselves are not phototoxic, but that coral metabolism glycosylates the hydroxyl groups to form glucoside metabolites that produce ROS and are thus phototoxic. Octinoxate and octocrylene should be directly phototoxic because they lack a hydroxyl group adjacent to the aromatic carbonyl. The research will employ both hard- and soft-coral adults but mainly use the sea anemone Aiptasia, a well characterized model system for corals; like corals, Aiptasia are anthozoans containing endosymbiotic photosynthetic algae. Objective 1 will characterize the mechanism of oxybenzone phototoxicity by: (i) testing whether the presence of oxybenzone leads to mortality only in the presence of the UV wavebands of sunlight, (ii) quantifying the conversion of oxybenzone to glucoside metabolites by the host animal and/or the symbiotic algae, (iii and iv) testing for ROS production under sunlight from glucoside metabolites (iii) in vitro and (iv) in vivo, and (v) quantifying mortality from exposure to glucoside analogues. Objective 2 will replicate these experiments with homosalate, octisalate, octinoxate, and octocrylene to characterize the relevance of this mechanism to sunscreen components being considered as alternatives to oxybenzone. Undergraduate students from underrepresented groups and a high-school science teacher with an accompanying student from an underrepresented group will be recruited to participate in summer research by partnering with existing Stanford University programs. The research should inform policy discussions about which components to regulate in sunscreens and be relevant to the management of coral-reef reserves.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

世界上很大一部分珊瑚礁面临着灭绝的危险。虽然大部分威胁是由全球因素造成的，但局部因素也会大大加剧珊瑚的下降。最近关注的焦点是氧苯酮，一种常见的防晒霜成分，因为观察到氧苯酮对成年珊瑚有毒，并减少幼珊瑚的存活率。造成这种毒性的原因尚不清楚，需要进一步了解，才能设计出对珊瑚礁真正安全的可持续防晒霜。本研究项目将描述对珊瑚造成光毒性的有机防晒成分或其代谢物的化学结构，重点关注五种最常见的有机防晒成分：氧苯酮、同盐酸盐、octisalate、octinoxate和octocrylene。这一改进的认识将为设计新的、可持续的、不表现出光毒性的防晒霜成分奠定基础。核心假设是，与芳香羰基相邻的羟基（存在于五种化合物中的每一种）的存在与否是防晒成分是否具有光毒性的关键决定因素。在阳光的吸收下，芳香羰基会形成激发态，产生活性氧（ROS），从而产生光毒性。然而，在氧苯酮、同盐酸盐和辛酸盐中，与芳香羰基相邻的羟基通过猝灭激发态三联体抑制阳光照射时ROS的产生。有初步证据支持的假设是，氧苯酮、同型盐酸盐和辛酸盐本身没有光毒性，但珊瑚代谢的糖基化羟基形成产生活性氧的糖苷代谢物，因此具有光毒性。辛皮酸酯和八烯烯应该是直接光毒性的，因为它们缺少一个与芳香羰基相邻的羟基。该研究将采用硬珊瑚和软珊瑚成年，但主要使用海葵Aiptasia，这是一种特征良好的珊瑚模型系统；和珊瑚一样，寄生藻是含有内生光合藻类的珊瑚虫。目标1将通过以下方式表征氧苯酮光毒性的机制：(i)测试氧苯酮的存在是否仅在阳光的紫外波段存在下导致死亡，（ii）量化宿主动物和/或共生藻类将氧苯酮转化为葡萄糖苷代谢物的过程，（iii和iv）测试阳光下葡萄糖苷代谢物产生的活性氧（iii）在体外和（iv）在体内，以及(v)量化暴露于葡萄糖苷类似物的死亡率。目的2将用同盐酸盐、辛酸盐、辛酸盐和八烯烯重复这些实验，以表征该机制与被认为是氧苯酮替代品的防晒成分的相关性。来自代表性不足群体的本科生和一名高中科学教师以及一名来自代表性不足群体的学生将被招募参加与斯坦福大学现有项目合作的暑期研究。这项研究应该为政策讨论提供信息，以确定防晒霜中哪些成分应该加以管制，并与珊瑚礁保护区的管理有关。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Conversion of oxybenzone sunscreen to phototoxic glucoside conjugates by sea anemones and corals

• DOI: 10.1126/science.abn2600
• 发表时间: 2022-05-06
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Vuckovic, Djordje;Tinoco, Amanda, I;Mitch, William A.
• 通讯作者: Mitch, William A.