Acute dermal toxicity, irritation, sensitization and in vitro mutagenicity studies of a topical cosmeceutical for protection against ultraviolet radiation
Creators: name: Bora, Nilutpal Sharma
name: Manash Pratim Pathak
name: Johirul Islam
name: Pompy Patowary
name: Mazumder, Bhaskar
name: Rudragoud S. Policegoudra
name: Pronobesh Chattopadhyay
Publisher: name: figshare
Year: 2020
Subjects: subject: 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 111504 Pharmaceutical Sciences

description: <b>Introduction</b> An estimated 6% of the total ultraviolet radiation generated by the sun reaches the earth’s surface, which is the major etiological agent of a variety of skin disorders including melanoma and non-melanoma cancer [1]. Sun protection products are designed to protect the user by absorbing or reflecting the sun’s UV radiation [2]. Chemophotoprotective agents have reported various allergic reaction like contact dermatitis, contact urticaria, photo-allergic and phototoxic reactions, and rare but evident cases of severe anaphylactic reactions [3]. The present study was undertaken to evaluate the acute dermal toxicity, skin irritating and sensitizing potential, and mutagenic property of a novel topical photoprotectant formulation; consisting mainly of avobenzone, octinoxate and oxybenzone as the active pharmaceutical ingredients. The formulation was loaded with pumpkin seed oil for protective aid and antioxidant efficacy. <b>Experimental</b> The acute dermal toxicity, skin irritating and sensitizing potential of the formulation were evaluated in rabbits, guinea pigs and rats in accordance with the OECD guidelines number 402, 404 and 406 respectively. In an attempt to further establish its safety profile the cosmeceutical was also assessed for mutagenic potential using TA1535 and TA1538 strains of <i>Salmonella typhimurium </i>by Ames test (OECD Test Guideline 471 recommendations, Ames and Whitfield spot test procedure) [4]. All the experimental protocols were approved by the IAEC and performed in compliance with the Principles of Laboratory Animal Care (NIH Publication 85-23, revised 1985). <b>Methods</b> Characterization of the formulations was done before the initiation of the study. In the primary skin irritation test, the test formulation was evaluated against the placebo formulation for 72 hours in rabbits for any signs of irritant properties. For the skin sensitization test, guinea pigs were tested for any hypersensitivity reactions by the active or placebo formulations for 24 hours, against the standard irritant 1-chloro-2,4-dinitrobenzene (CNDB). The acute dermal toxicity assay was carried out in adult rats by dermal application of both the test and placebo formulations over a period of 14 days. The mutagenic assays were performed by applying a small amount of the test and placebo formulations directly to the center of a selective agar medium plate seeded with the test organism. Revertant colonies were counted after 3 days of incubation at 37◦C temperature and compared to the number of spontaneous revertant colonies per plate. All the experiments were conducted in triplicates. <b>Results and Discussion</b> In the primary skin irritation test, the test and placebo formulations did not show any signs of irritation; hence the active formulation was classified as non irritant based on the primary irritation index score. Neither of the formulations induced any sensitization reaction as compared to the standard CDNB and therefore graded as weak in sensitization score and rate. The formulations did not exhibit any overt signs of toxicity when evaluated for their acute dermal toxicity. In Ames reverse mutation test, both the formulation and its placebo was not found to be mutagenic. However, the formulation was unable to produce any anti-mutagenic effects against sodium azide and 2-nitrofluorene. <b>Conclusion</b> The above findings indicate that the formulation is non-irritant and non-toxic as it does not exert any skin irritation, skin sensitization, or dermal toxicity effects. The study also suggests that the formulation is non mutagenic and safe for human use however further investigations regarding the genotoxic potential of the formulation is solicited.