{"abstract":"The Food and Drug Administration (FDA or the Agency) is issuing a proposed sunscreen order (proposed order) under the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Sunscreen Innovation Act (SIA). The proposed order announces FDA's tentative determination that enzacamene is not generally recognized as safe and effective (GRASE) and is misbranded when used in over-the- counter (OTC) sunscreen products because the currently available data are insufficient to classify it as GRASE and not misbranded, and additional information is needed to allow us to determine otherwise.","action":"Proposed order; request for comments.","agencies":[{"raw_name":"DEPARTMENT OF HEALTH AND HUMAN SERVICES","name":"Health and Human Services Department","id":221,"url":"https://www.federalregister.gov/agencies/health-and-human-services-department","json_url":"https://www.federalregister.gov/api/v1/agencies/221","parent_id":null,"slug":"health-and-human-services-department"},{"raw_name":"Food and Drug Administration","name":"Food and Drug Administration","id":199,"url":"https://www.federalregister.gov/agencies/food-and-drug-administration","json_url":"https://www.federalregister.gov/api/v1/agencies/199","parent_id":221,"slug":"food-and-drug-administration"}],"body_html_url":"https://www.federalregister.gov/documents/full_text/html/2015/02/25/2015-03884.html","cfr_references":[{"chapter":null,"citation_url":null,"part":310,"title":21}],"citation":"80 FR 10026","comment_url":null,"comments_close_on":"2015-04-13","correction_of":null,"corrections":[],"dates":"Submit either electronic or written comments on this proposed order by April 13, 2015. Sponsors may submit written requests for a meeting with FDA to discuss this proposed order by March 27, 2015. See section VI for the proposed effective date of a final order based on this proposed order.","disposition_notes":null,"docket_ids":["Docket Nos. FDA-2003-N-0196 (Formerly 2003N-0233), FDA-1978-N-0018 (Formerly 1978N-0038 and 78N-0038), and FDA-1996-N-0006 (Formerly 96N-0277)"],"dockets":[{"supporting_documents":[{"title":"Reference 208 - Kasichayanula_2005_Simultaneous Analysis of Insect Repellent DEET, Sunscreen Oxybenzone and Five Relevant Metabolites","document_id":"FDA-1978-N-0018-1049"},{"title":"Reference 196 - FDA_Food Additive Status List","document_id":"FDA-1978-N-0018-1037"},{"title":"Reference 193 - Katz_2008_Insect Repellants- Historical Perspectives and New Developments","document_id":"FDA-1978-N-0018-1034"},{"title":"Reference 190 - EPA_Using Insect Repellents Safely and Effectively","document_id":"FDA-1978-N-0018-1031"},{"title":"Reference 180 - TGA_2016_Australian regulatory guidelines for sunscreens","document_id":"FDA-1978-N-0018-1021"},{"title":"Reference 169 - Damian_2011_An action spectrum for UV radiation-induced immunosuppression in humans","document_id":"FDA-1978-N-0018-1010"},{"title":"Reference 153 - Liu_2017_Particle Size Distribution Analysis of OTC Drug Products with Unintended Inhalation Exposure to Consumers","document_id":"FDA-1978-N-0018-0994"},{"title":"Reference 148 - Stuart_1984_Deposition and Clearance of Inhaled Particles","document_id":"FDA-1978-N-0018-0989"},{"title":"Reference 134 - Rodriguez_2006_Causal agents of photoallergic contact dermatitis","document_id":"FDA-1978-N-0018-0975"},{"title":"Reference 99 - Gupta_1999_Percutaneous Absorption of Sunscreens through Micro-Yucatan Pig Skin in Vitro","document_id":"FDA-1978-N-0018-0939"}],"agency_name":"FDA","documents":[{"comment_count":5,"comment_start_date":"2015-02-25","updated_at":"2023-02-28T20:18:54.733-05:00","comment_url":"https://www.regulations.gov/commenton/FDA-1978-N-0018-0775","allow_late_comments":null,"id":"FDA-1978-N-0018-0775","comment_end_date":"2015-04-14","regulations_dot_gov_open_for_comment":false}],"supporting_documents_count":325,"id":"FDA-1978-N-0018","title":"Sunscreen Drug Products -OPEN"},{"supporting_documents":[{"title":"Background Material Specific Questions for FDA from Holland&Knight","document_id":"FDA-1996-N-0006-0188"},{"title":"Attachment 3 American Academy Of Dermatology, Sun Protection re Comment from Merck KGaA","document_id":"FDA-1996-N-0006-0180"},{"title":"Attachment 3 Ostroff, The Bottom Line On ASIA re Comment from Merck KGaA","document_id":"FDA-1996-N-0006-0179"},{"title":"Attachment 4 Review Of Over The Counter Active Ingredients re Comment from Merck KGaA","document_id":"FDA-1996-N-0006-0178"},{"title":"Attachment 5 Conference Report re Comment from Merck KGaA","document_id":"FDA-1996-N-0006-0177"},{"title":"Reference 9 CP1, 81N-0033 re Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug","document_id":"FDA-1996-N-0006-0176"},{"title":"Reference 5 CP2, 78N-0038 re Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug","document_id":"FDA-1996-N-0006-0168"},{"title":"Reference 4 CP1, 78N-0038 re Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug","document_id":"FDA-1996-N-0006-0167"},{"title":"List of References re Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug Monograph System","document_id":"FDA-1996-N-0006-0166"},{"title":"Reference 30 - International Conference on Harmonization (ICH) Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies S3A, March 1995 re Over-the-Counter Sunscreen Drug Products - Regulatory Status of Enzacamene","document_id":"FDA-1996-N-0006-0130"}],"agency_name":"FDA","documents":[{"comment_count":0,"comment_start_date":"2015-02-25","updated_at":"2023-02-28T20:18:52.814-05:00","comment_url":"https://www.regulations.gov/commenton/FDA-1996-N-0006-0100","allow_late_comments":null,"id":"FDA-1996-N-0006-0100","comment_end_date":"2015-04-14","regulations_dot_gov_open_for_comment":false}],"supporting_documents_count":60,"id":"FDA-1996-N-0006","title":"Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug Monograph System"},{"supporting_documents":[{"title":"Reference 30 - International Conference on Harmonization (ICH) Toxicokinetics:  The Assessment of Systemic Exposure in Toxicity Studies S3A, March 1995 re Over-the-Counter Sunscreen Drug Products—Regulatory Status of Enzacamene","document_id":"FDA-2003-N-0196-0090"},{"title":"Reference 29 - International Conference on Harmonization (ICH)  Harmonized Tripartite Guideline for Industry, Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility S5(R2), 2005 re Over-the-Counter Sunscreen Drug Product","document_id":"FDA-2003-N-0196-0089"},{"title":"Reference 28 - International Conference on Harmonization (ICH) Guidance for Industry - S1C(R2) Dose Selection for Carcinogenicity Studies of Pharmaceuticals SIC(R2) (Revision 1), September 2008 re Over-the-Counter Sunscreen Drug Products—Regulatory Status","document_id":"FDA-2003-N-0196-0088"},{"title":"Reference 27 - Guidance for Industry, S1B Testing for Carcinogenicity of Pharmaceuticals, July 1997 re Over-the-Counter Sunscreen Drug Products—Regulatory Status of Enzacamene","document_id":"FDA-2003-N-0196-0087"},{"title":"Reference 26 - International Conference on Harmonization (ICH), Guidance for Industry, The Need for Long Term Rodent Carcinogenicity Studies of Pharmaceuticals S1A, March 1996 re Over-the-Counter Sunscreen Drug Products—Regulatory Status of Enzacamene","document_id":"FDA-2003-N-0196-0086"},{"title":"Reference 25 - Schlumpf et al, Endocrine Activity and Developmental Toxicity of Cosmetic UV Filters-An Update re Over-the-Counter Sunscreen Drug Products—Regulatory Status of Enzacamene","document_id":"FDA-2003-N-0196-0085"},{"title":"Reference 24 - Schlumpf et al, Estrogenic Activity and Estrogen Receptor Beta Binding of the UV Filter 3-Benzylidene Camphor. Comparison With 4-Methylbenzylidene Camphor re Over-the-Counter Sunscreen Drug Products—Regulatory Status of Enzacamene","document_id":"FDA-2003-N-0196-0084"},{"title":"Reference 23 - Schlumpf et al, In Vitro and In Vivo Estrogenicity of UV Screens re Over-the-Counter Sunscreen Drug Products—Regulatory Status of Enzacamene","document_id":"FDA-2003-N-0196-0083"},{"title":"Reference 22 - Maerkel et al, Sex- and Region-Specific Alterations of Progesterone Receptor mRNA Levels and Estrogen Sensitivity in Rat Brain Following Developmental Exposure to the Estrogenic UV Filter 4-Methylbenzylidene Camphor re Over-the-Counter Suns","document_id":"FDA-2003-N-0196-0082"},{"title":"Reference 21 - Maerkel et al, Sexually Dimorphic Gene Regulation in Brain as a Target for Endocrine Disrupters:  Developmental Exposure of Rats to 4-Methylbenzylidene Camphor re Over-the-Counter Sunscreen Drug Products—Regulatory Status of Enzacamene","document_id":"FDA-2003-N-0196-0081"}],"agency_name":null,"documents":[{"comment_count":3,"comment_start_date":"2015-02-25","updated_at":"2023-02-28T20:18:55.243-05:00","comment_url":"https://www.regulations.gov/commenton/FDA-2003-N-0196-0060","allow_late_comments":null,"id":"FDA-2003-N-0196-0060","comment_end_date":"2015-04-14","regulations_dot_gov_open_for_comment":false}],"supporting_documents_count":62,"id":"FDA-2003-N-0196","title":"Over-the-Counter Drug Products; Safety and Efficacy Review; Additional Sunscreen Ingredients"}],"document_number":"2015-03884","effective_on":null,"end_page":10035,"executive_order_notes":null,"executive_order_number":null,"full_text_xml_url":"https://www.federalregister.gov/documents/full_text/xml/2015/02/25/2015-03884.xml","html_url":"https://www.federalregister.gov/documents/2015/02/25/2015-03884/over-the-counter-sunscreen-drug-products-regulatory-status-of-enzacamene","images":{},"images_metadata":{},"json_url":"https://www.federalregister.gov/api/v1/documents/2015-03884?publication_date=2015-02-25","mods_url":"https://www.govinfo.gov/metadata/granule/FR-2015-02-25/2015-03884/mods.xml","not_received_for_publication":null,"page_length":10,"page_views":{"count":2536,"last_updated":"2026-10-24 18:15:05 -0400"},"pdf_url":"https://www.govinfo.gov/content/pkg/FR-2015-02-25/pdf/2015-03884.pdf","presidential_document_number":null,"proclamation_number":null,"public_inspection_pdf_url":"https://public-inspection.federalregister.gov/2015-03884.pdf?1424785770","publication_date":"2015-02-25","raw_text_url":"https://www.federalregister.gov/documents/full_text/text/2015/02/25/2015-03884.txt","regulation_id_number_info":{},"regulation_id_numbers":[],"regulations_dot_gov_info":{"supporting_documents":[{"title":"Background Material Specific Questions for FDA from Holland&Knight","document_id":"FDA-1996-N-0006-0188"},{"title":"Attachment 3 American Academy Of Dermatology, Sun Protection re Comment from Merck KGaA","document_id":"FDA-1996-N-0006-0180"},{"title":"Attachment 3 Ostroff, The Bottom Line On ASIA re Comment from Merck KGaA","document_id":"FDA-1996-N-0006-0179"},{"title":"Attachment 4 Review Of Over The Counter Active Ingredients re Comment from Merck KGaA","document_id":"FDA-1996-N-0006-0178"},{"title":"Attachment 5 Conference Report re Comment from Merck KGaA","document_id":"FDA-1996-N-0006-0177"},{"title":"Reference 9 CP1, 81N-0033 re Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug","document_id":"FDA-1996-N-0006-0176"},{"title":"Reference 5 CP2, 78N-0038 re Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug","document_id":"FDA-1996-N-0006-0168"},{"title":"Reference 4 CP1, 78N-0038 re Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug","document_id":"FDA-1996-N-0006-0167"},{"title":"List of References re Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug Monograph System","document_id":"FDA-1996-N-0006-0166"},{"title":"Reference 30 - International Conference on Harmonization (ICH) Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies S3A, March 1995 re Over-the-Counter Sunscreen Drug Products - Regulatory Status of Enzacamene","document_id":"FDA-1996-N-0006-0130"}],"regulatory_plan":{"html_url":"https://www.federalregister.gov/regulations/0910-AA01/over-the-counter-otc-drug-review","title":"Over-the-Counter (OTC) Drug Review"},"comments_count":0,"agency_id":"FDA","comments_url":"https://www.regulations.gov/docketBrowser?rpp=50&so=DESC&sb=postedDate&po=0&dct=PS&D=FDA-1996-N-0006","supporting_documents_count":60,"docket_id":"FDA-1996-N-0006","document_id":"FDA-1996-N-0006-0100","regulation_id_number":"0910-AA01","title":"Eligibility Criteria for Considering Additional Conditions in the Over-the-Counter Drug Monograph System","checked_regulationsdotgov_at":"2023-03-01T01:18:51Z"},"regulations_dot_gov_url":null,"significant":null,"signing_date":null,"start_page":10026,"subtype":null,"title":"Over-the-Counter Sunscreen Drug Products-Regulatory Status of Enzacamene","toc_doc":"Status of Enzacamene","toc_subject":"Over-the-Counter Sunscreen Drug Products:","topics":[],"type":"Proposed Rule","volume":80}