Investigating the effects of dermal exposure to in-vivo animal models on the riot-control properties of a powder formulation of Tragia involucrata leaf hair lining.

Purpose: Riot control agents (RCAs) such as CS, CN, CR, PAVA, and OC, etc., are already in use and has produced numerous health risks, including skin burns, dermatitis, gastrointestinal issues, impairment of respiratory variables, conjunctivitis, etc., and even prolonged and repeated exposure may cause death. Therefore, there is a demand and need for non-lethal, non-toxic RCAs that can effectively control riots without resulting in fatal outcomes. This study was carried out to evaluate the health risks related to a novel formulation made from isolated Tragia involucrata leaf hair lining, that can be used as the best suitable non-lethal RCAs.Methods: According to the OECD guidelines, studies on acute dermal toxicity, dermal irritation/corrosion, and skin sensitisation were carried out. Wistar rats were used in an acute dermal toxicity study, and the results indicated no mortality, morbidity, or abnormal food-and-water intake, biochemical parameters, or histopathological examination findings. A study on dermal irritation in Rabbits produced moderate erythema and the effect was instantaneous and resolved within 72 hrs of post-exposure. A skin sensitisation test was conducted on Guinea pig.Results: The results showed that the formulation had moderate skin-sensitizing properties after the application of the challenge dose. Patchy erythema was seen, and it went away 30 hrs after the gauze patch was removed.Conclusion: The preclinical results did not produce any indication of severe toxicity which supports it to be used as a natural RCAs in the future.

Optimization of the extraction conditions and dermal toxicity of oil body fused with acidic fibroblast growth factor (OLAF).

INTRODUCTION: Oil body (OB), a subcellular organelle that stores oil in plant seeds, is considered a new transdermal drug delivery system. With the increasing understanding of the OB and its main protein (oleosin), numerous studies have been conducted on OB as "carrier" for the expression of exogenous proteins. In our previous study, oil body fused with aFGF (OLAF) was obtained using a plant oil body expression system that had been preliminarily proven to be effective in accelerating the healing of skin wounds. However, no dermal toxicological information on OLAF is available. OBJECTIVE: To ensure the dermal safety of OLAF, a series of tests (the acute dermal toxicity test, 21-day repeat dermal toxicity test, dermal irritation test and skin sensitisation test) were conducted after optimising the extraction protocol of OLAF. MATERIALS AND METHODS: To improve the extraction rate of OLAF, response surface methodology (RSM) was first employed to optimise the extraction conditions. Then, Wistar rats were exposed to OLAF (400 mg·kg-1 body weight) in two different ways (6 hours/time for 24 hours and 1 time/day for 21 days) to evaluate the acute dermal toxicity and 21-day repeated dermal toxicity of OLAF. In the acute dermal toxicity test, clinical observations were conducted to evaluate the toxicity, behaviour, and health of the animals for 14 consecutive days. Similarly, the clinical signs, body weight, haematological and biochemical parameters, histopathological changes and other indicators were also detected during the 21 days administration. For the dermal irritation test, single and multiple doses of OLAF (125 mg·kg-1 body weight) were administered to albino rabbits for 14 days (1 time/day). The irritation reaction on the skin of each albino rabbit was recorded and scored. Meanwhile, skin sensitisation to OLAF was conducted using guinea pigs for a period of 28 days. RESULTS: Suitable extraction conditions for OLAF (PBS concentration 0.01, pH of PBS 8.6, solid-liquid ratio 1:385 g·mL-1) were obtained using RSM. Under these conditions, the extraction rate and particle size of OLAF were 7.29% and 1290 nm, respectively. In the tests of acute dermal toxicity and 21-day repeated dermal toxicity, no mortality or significant differences were observed in terms of clinical signs, body weight, haematological parameters, biochemical parameters and anatomopathological analysis. With respect to the dermal irritation test and skin sensitisation test, no differences in erythema, oedema or other abnormalities were observed between treatment and control groups on gross and histopathological examinations. CONCLUSIONS: The results of this study suggest that OLAF does not cause obvious toxicity, skin sensitisation or irritation in animals.

Safety profile of silver sulfadiazine-bFGF-loaded hydrogel for partial thickness burn wounds.

In the present investigation, the safety of novel combinational silver sulfadiazine-bFGF-loaded hydrogel was assured by performing acute skin irritation, sensitization, acute dermal toxicity, and eye irritation in compliance with the Organization for Economic Co-operation and Development guidelines. In the skin irritation study, placebo, test, and positive control (0.8% w/v aqueous solution of formaldehyde) were applied on New Zealand rabbits and monitored for abnormal skin responses including erythema and edema. The placebo and test formulation did not induce any adverse reactions and were classified as nonirritating materials. In the skin sensitization test, guinea pigs were sensitized by positive control (0.1% w/v 1-chloro-2,4-dinitrobenzene in 10% of propylene glycol as a standard skin sensitizing agent), placebo, and test formulations. Weak sensitization was observed in the placebo and test formulation treated groups. Additionally, acute dermal toxicity test was performed in Wistar rats, where no signs of toxicity were observed in biochemical, hematological, and histopathological studies. Moreover, the acute eye irritation test was carried out in rabbits and no abnormal clinical signs were evident in the cornea or iris. As a whole, these findings suggest that the hydrogel formulation does not cause any skin irritation, skin sensitizationand dermal toxic effects, and eye irritation following dermal and ocular applications, respectively. Therefore, all the findings obtained from this preclinical study indicated that this hydrogel formulation is nontoxic and safe for use in animal models.

Evaluation of a tiered in vitro testing strategy for assessing the ocular and dermal irritation/corrosion potential of pharmaceutical compounds for worker safety.

INTRODUCTION: Irritation reactions are a frequently reported occupational illness. The potential adverse effects of pharmaceutical compounds (PCs) on eye and skin can now be assessed using validated in vitro methods. OBJECTIVES: Our overall aim is to reduce animal testing by replacing the historically utilized in vivo test methods with validated in vitro test methods which accurately determine the ocular and dermal irritation/corrosion potential of PCs to inform worker safety within the pharmaceutical space. Bristol-Myers Squibb (BMS) and the Institute for In Vitro Sciences (IIVS) have therefore conceptualized and internally qualified a tiered in vitro testing strategy to inform occupational hazards regarding eye and skin irritation and corrosivity of PCs. For the small scale pre-qualification phase, we paired historical in vivo and newly generated in vitro data for 15 PCs to determine the predictive capacity of in vitro assays already validated for the eye and skin irritation/corrosion endpoints and accepted for certain regulatory submissions. During the post-qualification phase, a group of 24 PCs were subjected exclusively to the developed tiered testing strategy, which is based on three Organisation for Economic Co-operation and Development (OECD) in vitro methods. MATERIALS AND METHODS: The qualified in vitro testing strategy utilizes the Corrositex® assay for the corrosivity (OECD TG 435), the Bovine Corneal Opacity and Permeability (BCOP) assay for ocular irritation (OECD TG 437), and the EpiDerm™ tissue model-based Skin Irritation Test (SIT) for dermal irritation (OECD TG 439). In the first step, the pH of each PC was determined. For compounds with pH extremes ≥11 or ≤2, the Corrositex® assay was generally conducted first. For compound(s) that were incompatible with or were negative in the Corrositex® assay or had pH values between 2 and 11, the BCOP assay and SIT were performed first. RESULTS: The results of the tiered testing strategy's qualification phase demonstrated that the BCOP assay is sensitive enough to identify a wide range of eye irritation/corrosion potentials and its over-prediction rate was considered acceptable to inform occupational hazards and ensure the proper handling practices of PCs. The SIT correctly predicted the skin irritation potential of 14 out of the 15 PCs included in the qualification phase, only over-predicting one PC. In the post-qualification phase, four PCs out of four tested were predicted corrosive by the Corrositex® assay and thus no further testing was needed or conducted. The rest of the PCs were evaluated in the BCOP assay (both neat and as a 20% dilution), with the higher response being used for hazard classification. Four PCs were determined to be severe eye irritants, 1 a moderate irritant, 8 were mild irritants, and 8 were non-irritants. The same set of PCs was evaluated using the SIT and were classified as non-irritants to skin. These results are consistent with the BMS historical in vivo results showing a very low number of PCs as skin irritants. CONCLUSIONS: This tiered in vitro testing strategy, which replaces the use of animal studies, was found to be reasonably accurate in its predictive capacity when compared to historical in vivo results and represents a conservative and reliable platform that can be utilized for the prediction of ocular and dermal irritation/corrosion potential of PCs and for subsequent GHS classification and worker safety hazard communications.

Safety, Efficacy, and Physicochemical Characterization of Tinospora crispa Ointment: A Community-Based Formulation against Pediculus humanus capitis.

The high prevalence of pediculosis capitis, commonly known as head lice (Pediculus humanus capitis) infestation, has led to the preparation of a community-based pediculicidal ointment, which is made of common household items and the extract of Tinospora crispa stem. The present study aimed to evaluate the safety, efficacy, and physicochemical characteristics of the T. crispa pediculicidal ointment. The physicochemical properties of the ointment were characterized, and safety was determined using acute dermal irritation test (OECD 404), while the efficacy was assessed using an in vitro pediculicidal assay. Furthermore, the chemical compounds present in T. crispa were identified using liquid-liquid extraction followed by ultra-performance liquid chromatography quadruple time-of-flight mass spectrometric (UPLC-qTOF/MS) analysis. The community-based ointment formulation was light yellow in color, homogeneous, smooth, with distinct aromatic odor and pH of 6.92±0.09. It has spreadability value of 15.04±0.98 g·cm/sec and has thixotropic behavior. It was also found to be non-irritant, with a primary irritation index value of 0.15. Moreover, it was comparable to the pediculicidal activity of the positive control Kwell®, a commercially available 1% permethrin shampoo (P>0.05), and was significantly different to the activity of the negative control ointment, a mixture of palm oil and candle wax (P<0.05). These findings suggested that the community-based T. crispa pediculicidal ointment is safe and effective, having acceptable physicochemical characteristics. Its activity can be attributed to the presence of compounds moupinamide and physalin I.

Morphological analysis of patchy thickening and reddish discoloration of active hair growth areas in the skin of New Zealand White rabbits.

Patchy thickening and reddish discoloration of active hair growth areas of skin in rabbits are occasionally found, and this gross feature could affect precise evaluation when conducting a dermal irritation test. Since little is known about the mechanism of this phenomenon, we examined the dorsal skin of New Zealand White rabbits morphologically and immunohistochemically in order to identify the possible mechanism responsible for developing these skin changes in relation to the hair cycle. Skin samples from 4 rabbits were divided into three groups (5 samples/group) based on their macroscopic characteristics: a thickened skin, erythematous skin, and smooth skin group. Histomorphological examination revealed that the percentage of hair follicles in the anagen phase, hair follicle length, hair follicle area, and proliferating cell nuclear antigen-positive cells in the hair follicles were greater in the thickened skin and erythematous skin groups than in the smooth skin group. Unlike mice and rats, the dermis was nearly adjacent to the muscular layer with a thin hypodermis, and the whole lengths of hair follicles in the anagen phase were located in the dermis in the rabbit skin. These results suggest that large hair follicles in the anagen phase compressed the surrounding dermis; therefore, the skin was grossly raised and showed thickening. A higher number of CD31-positive blood vessels, suggesting the occurrence of angiogenesis, was observed around the hair follicles in the erythematous skin group, and they seemed to affect the reddish discoloration of skin noted grossly.

Evaluation of electric arc furnace-processed steel slag for dermal corrosion, irritation, and sensitization from dermal contact.

Electric arc furnace (EAF) steel slag is alkaline (pH of ~11-12) and contains metals, most notably chromium and nickel, and thus has potential to cause dermal irritation and sensitization at sufficient dose. Dermal contact with EAF slag occurs in many occupational and environmental settings because it is used widely in construction and other industrial sectors for various applications including asphaltic paving, road bases, construction fill, and as feed for cement kilns construction. However, no published study has characterized the potential for dermal effects associated with EAF slag. To assess dermal irritation, corrosion and sensitizing potential of EAF slag, in vitro and in vivo dermal toxicity assays were conducted based on the Organisation for Economic Co-operation and Development (OECD) guidelines. In vitro dermal corrosion and irritation testing (OECD 431 and 439) of EAF slag was conducted using the reconstructed human epidermal (RHE) tissue model. In vivo dermal toxicity and delayed contact sensitization testing (OECD 404 and 406) were conducted in rabbits and guinea pigs, respectively. EAF slag was not corrosive and not irritating in any tests. The results of the delayed contact dermal sensitization test indicate that EAF slag is not a dermal sensitizer. These findings are supported by the observation that metals in EAF slag occur as oxides of low solubility with leachates that are well below toxicity characteristic leaching procedure (TCLP) limits. Based on these results and in accordance to the OECD guidelines, EAF slag is not considered a dermal sensitizer, corrosive or irritant.

Dermal irritation of petrolatum in rabbits but not in mice, rats or minipigs.

Petrolatum is widely used in cosmetics, topical pharmaceuticals and also as a vehicle in dermal toxicity studies. New Zealand white rabbits treated with white petrolatum (vehicle control) in a 2-week dermal irritation study exhibited moderate to severe erythema starting on Day 7 that subsided towards the end of the study. Histological examination of abraded and non-abraded petrolatum-treated skin obtained at termination (Day 15) revealed mild acanthosis, hyperkeratosis, dermal edema with mixed inflammatory cells in the dermis. Macroscopic and microscopic features noted in rabbits were consistent with dermal irritation to petrolatum. Wistar-Han rats, CD1 mice, C57/Bl/6J mice and Göttingen minipigs treated topically with white petrolatum did not exhibit clinical or histologic evidence of dermal irritation. Therapeutic agents developed for topical application are generally tested in rabbits during some point in development. Interpretation of skin irritation data from a single species can impact risk assessment for humans and on product labeling.

Acute dermal irritation, sensitization, and acute toxicity studies of a transdermal patch for prophylaxis against ({+/-}) anatoxin-a poisoning.

The skin irritating, sensitizing, and acute dermal toxicity potential of a novel combinational prophylactic transdermal patch, mainly composed of eserine and pralidoxime chloride as active pharmaceutical ingredients, against (±) anatoxin-a poisoning were investigated in rabbits, guinea pigs, and rats in compliance with the Organisation for Economic Cooperation and Development guidelines. In primary skin irritation test, rabbits were dermally attached with the therapeutically active transdermal patch or with a placebo patch for 72 hours. The transdermal patches did not induce any adverse reactions such as erythema and edema on intact skin sites. The active patch was classified as a practically nonirritating material based on the score in the primary irritation index. In the Buehler test, guinea pigs were sensitized by the active or placebo transdermal patches attached for 24 hours. The patches did not induce any sensitization reactions in contrast to a severe sensitization reaction that occurred in the positive control. Therefore, the active patch and placebo patch were both graded as weak in sensitization score and rate. Acute dermal toxicity test in rats did not produce any overt signs of toxicity following a 14-day treatment period. Taken together, these findings suggest that the transdermal patch does not cause skin irritation, skin sensitization, or dermal toxic effects following dermal application.

Saline extract of Portulaca elatior leaves with photoprotective and antioxidant activities does not show acute oral and dermal toxicity in mice.

The present study aimed to evaluate saline extracts from the leaves (LE) and stem (SE) of Portulaca elatior in relation to their phytochemical composition and photoprotective and antioxidant effects, as well as to evaluate the toxicity of the leaf extract. The extracts were characterized for protein concentration and phenol and flavonoid contents, as well as for thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) profiles. Total antioxidant capacity and DPPH and ABTS+ scavenging activities were determined. In the photoprotective activity assay, the sun protection factor (SPF) was calculated. The toxicity evaluation of LE included in vitro hemolytic assay and in vivo oral and dermal acute toxicity assays in Swiss mice. LE showed the highest protein, phenol, and flavonoid (8.79 mg/mL, 323.46 mg GAE/g, and 101.96 QE/g, respectively). TLC revealed the presence of flavonoids, reducing sugars, terpenes, and steroids in both extracts. In HPLC profiles, LE contained flavonoids, while SE contained flavonoids and ellagic tannins. The antioxidant activity assays showed the lowest IC50 values ​(34.15-413.3 µg/mL) for LE, which presented relevant SPF (> 6) at 50 and 100 µg/mL. LE demonstrated low hemolytic capacity, and no signs of intoxication were observed in mice treated orally or topically at 1000 mg/kg. However, at 2000 mg/kg, an increase in the mean corpuscular volume of erythrocytes and a reduction in lymphocytes were observed; animals treated topically with 2000 mg/kg displayed scratching behavior during the first hour of observation and showed edema and erythema that regressed after six days. In conclusion, LE did not present acute oral or dermal toxicity in Swiss mice at a dose of 1000 mg/kg and showed slight toxicity in animals treated with 2000 mg/kg. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00160-2.

Surfactin-Conjugated Silver Nanoparticles as an Antibacterial and Antibiofilm Agent against Pseudomonas aeruginosa.

The emergence of antimicrobial resistance is an alarming global health concern and has stimulated the development of novel functional nanomaterials to combat multi-drug-resistant (MDR) bacteria. In this work, we demonstrate for the first time the synthesis and application of surfactin-coated silver nanoparticles as an efficient antibacterial and antibiofilm agent against the drug-resistant bacteria Pseudomonas aeruginosa for safe dermal applications. Our in vivo studies showed no significant superficial dermal irritation, edema, and erythema, while microscopic analysis revealed that surfactin-coated silver nanoparticles caused no pathological alterations at the applied concentrations. These results support the potential use of surfactin-coated silver nanoparticles against drug-resistant bacterial biofilm infections and in skin wound dressing applications.

In vitro and In vivo study targeting the development of Unani Antidermatophytic Cream: Implication of Herbal Formulations in Treatment of Dermatophytosis.

Panwad (Cassia tora L.), Sarshaf (Brassica nigra L.) and Kunjad (Sesamum indicum L.) have been used in the treatment of ringworm infection since ancient times and are documented in classical literature of Unani Medicine. These plant drugs give promising results when used topically in the form of paste (zimad). Hence, the development and evaluation of a cream containing extracts of Tukhm-e-Panwad (Cassia tora L.), Sarshaf (Brassica nigra L.), and Kunjad (Sesamum indicum L.) was carried out to get better efficacy of the drugs. A total of 16 batches (F1-F16) of cream were prepared by adding varying concentrations of hydro-alcoholic extract of the drugs (20%, 40% and 50%) in water removable bases, and three batches were selected as final batches (F4-20%, F6-40% and F16-50%). In vitro antidermatophytic activity was conducted to optimize MIC against dermatophytosis-causing fungi. Dermal irritation of the prepared cream was determined in New Zealand Albino Rabbits. In vivo testing of the different concentrations of the prepared cream (20%, 40%, and 50%) was also carried out using Wistar rats to assess the antidermatophytic activity. Final batches showed good results in all the tested parameters and significant in vitro and in vivo antifungal activity in a dose-dependent manner. No microbial growth was seen in the prepared formulation. The study revealed significant antidermatophytic activity of the prepared cream against dermatophytosis-causing fungi. Hence, it can be concluded that the prepared cream can be an alternative topical agent with safe and effective antifungal activity for treating dermatophytosis.

Assessing the skin irritation and sensitizing potential of concentrates of water chlorinated in the presence of iodinated X-ray contrast media.

Chemical disinfection of water provides significant public health benefits. However, disinfectants like chlorine can react with naturally occurring materials in the water to form disinfection byproducts (DBPs). Natural levels of iodine have been reported to be too low in some source waters to account for the levels of iodinated DBPs detected. Iodinated X-ray contrast media (ICM) have been identified as a potential source of iodine. The toxicological impact of ICM present in source water at the time of disinfection has not been fully investigated. Iopamidol, iohexol, iopromide, and diatrizoate are among the ICM most frequently detected in water. In this study, source water containing one of these four ICM was chlorinated; non-chlorinated ICM-containing water samples served as controls. Reactions were conducted at an ICM concentration of 5 µM and a chlorine dose of 100 µM over 72 hr. Water concentrates (20,000-fold) were prepared by XAD-resin/ethyl acetate extraction and DMSO solvent exchange. We used the MatTek® reconstituted human epithelial skin irritation model to evaluate the water concentrates and also assessed the dermal irritation and sensitization potential of these concentrates using the LLNA:BrdU ELISA in BALB/c mice. None of the water concentrates tested (2500X) resulted in a skin irritant response in the MatTek® skin irritation model. Likewise, none of the concentrates (2500X, 1250X, 625X, 312.5X, 156.25X) produced a skin irritation response in mice: erythema was minimal; the maximum increase in ear thickness was less than 25%. Importantly, none of the concentrates produced a positive threshold response for allergic skin sensitization at any concentration tested in the LLNA:BrdU ELISA. We conclude that concentrates of water disinfected in the presence of four different ICM did not cause significant skin irritation or effects consistent with skin sensitization at the concentrations tested.

Evaluation of dermal corrosion and irritation by Cytoreg in rabbits.

Cytoreg is an experimental therapeutic platform consisting of an aqueous solution of six acids (hydrofluoric, hydrochloric, sulfuric, phosphoric, citric, and oxalic) with oncolytic, antiviral, immune modulatory and antibacterial activities. Cytoreg may be formulated for topical, oral, and parenteral administration. In the present study, a skin corrosion/irritation screen was conducted on three albino rabbits for the Cytoreg topical formulation at three dilutions; one animal each received a dilution of 100 %, 4 %, or 2 % in physiological saline solution. Three intact skin test sites per animal/concentration were evaluated. Each test site was treated with 0.5 mL of the appropriate test substance solution. Site one was dosed for 3 min, then observed. Dose site two was wrapped for 1 h, then both first and second test sites were observed. Dose site three was wrapped for 4 h. One hour after unwrapping the third site, all three test sites were observed for skin irritation and/or corrosion, and again at 24, 48 and 72 h after final unwrap. Based on the 4 -h dose scores through 72 h, the primary irritation index (PII) for Cytoreg is 0.00 at 2 % and 4 %, with a descriptive rating of non-irritating, and 0.25 PII with slightly irritating rating at 100 %.

Acute dermal toxicity study of new, used and laboratory aged aircraft engine oils.

There is little data available on toxicity levels of used aircraft engine oils relative to their unused (new) versions. This study was conducted to determine if new engine oils and their used versions have the potential to induce dermal irritation. Twelve male New Zealand White rabbits (Oryctolagus cuniculus, 19 weeks old) were used to determine the acute dermal toxicity potential of four aircraft turbine oils including MIL-PRF-7808 Grades 3 and 4 and MIL-PRF-23699 Grade 5 High Thermal Stability (HTS) and a Grade 5 experimental aircraft engine oil in their unused and used or laboratory stressed states. Five fur-free test sites (6 cm2 each) located lateral to the midline of the back were treated with two undiluted (0.5 ml) new engine oils and their used versions. The fifth site received reverse osmosis deionized (RODI) water as a control. Each treatment was repeated 3 times (3 rabbits/oil type). Each oil was tested under both semi-occluded and occluded conditions. The 4 h exposure was followed by gauze plus wrappings removal, and gentle cleaning of sites prior to scoring for erythema and edema at 0.5-1, 24, 48 and 72 h post exposure based on Draize (1959). E-collars were placed on each animal for at least 72 h to prevent ingestion of the test substance and/or gauze and wrappings and/or disturbance of site recovery. Additional observations were made on days 7, 10 and 14 to determine recovery. Exposure to both used and new oils produced dermal irritation consisting of no more than very slight to well-defined erythema and very slight edema. The calculated Primary Dermal Irritation Index (PDII) indicated that all the oils were slightly irritating (means ranged from 0.42 to 1.08). Although the PDII values for new oils and their used versions were not significantly different from each other, they were all statistically higher (p < 0.05) than those obtained for the control regardless of the type of occlusion binding applied. The used oils under semi-occlusion conditions yielded larger size effects (Cohen's d) relative to their unused versions suggesting an enhancement in irritation when the oil is aging. Grade 4 in the used state yielded the largest size effect which was d = 5.9 versus 2.6 for its unused version. The slight dermal irritation resulting from four hours of exposure to oils raises concerns about the magnitude of impact related to prolonged and/or repeated exposure.

Evaluation of dermal irritation and skin sensitization due to vitacoxib.

The prediction of side-effects is a key issue in the REACH initiative on chemicals in the preclinical testing of drugs. The dermal irritation and skin sensitization toxicity potential of a new molecule, vitacoxib, were invested in rabbits and guinea pigs in compliance with the Organization for Economic Cooperation and Development guideline. To assess dermal irritation, rabbits were dermally attached to vitacoxib for 72 h or repeated application. The results showed that no adverse reactions such as erythema and edema were observed throughout the test. In skin sensitization test, guinea pigs were sensitized to vitaoxib, positive and negative article for 24 h. No sensitization reaction was shown in the vitacoxib and negative group whereas severe sensitization was observed in the positive group. Based on these findings, vitacoxib does not cause dermal irritation and skin sensitization toxicity, and seems to be safe for animal use.

Confirmation of in vitro and clinical safety assessment of behentrimonium chloride-containing leave-on body lotions using post-marketing adverse event data.

Behentrimonium chloride (BTC) is a straight-chain alkyltrimonium chloride compound commonly used as an antistatic, hair conditioning, emulsifier, or preservative agent in personal care products. Although the European Union recently restricted the use of alkyltrimonium chlorides and bromides as preservatives to ≤0.1%, these compounds have been safely used for many years at ≤5% in hundreds of cosmetic products for other uses than as a preservative. In vitro, clinical, and controlled consumer usage tests in barrier-impaired individuals were conducted to determine if whole body, leave-on skin care products containing 1-5% BTC cause dermal irritation or any other skin reaction with use. BTC-containing formulations were predicted to be non-irritants by the EpiDerm® skin irritation test and the bovine corneal opacity and permeability (BCOP)/chorioallantoic membrane vascular assay (CAMVA) ocular irritation test battery. No evidence of allergic contact dermatitis or cumulative dermal irritation was noted under the exaggerated conditions of human occlusive patch tests. No clinically assessed or self-reported adverse reactions were noted in adults or children with atopic, eczematous, and/or xerotic skin during two-week and four-week monitored home usage studies. These results were confirmed by post-marketing data for five body lotions, which showed only 0.69 undesirable effects (mostly skin irritation) reported per million shipped consumer units during 2006-2011; a value consistent with a non-irritating body lotion. No serious undesirable effects were reported during in-market use of the products. Therefore, if formulated in appropriate conditions at 1-5%, BTC will not cause dermal irritation or delayed contact sensitization when used in a whole-body, leave-on product.

Safety, Efficacy, and Physicochemical Characterization of Tinospora crispa Ointment: A Community-Based Formulation against Pediculus humanus capitis

The high prevalence of pediculosis capitis, commonly known as head lice (Pediculus humanus capitis) infestation, has led to the preparation of a community-based pediculicidal ointment, which is made of common household items and the extract of Tinospora crispa stem. The present study aimed to evaluate the safety, efficacy, and physicochemical characteristics of the T. crispa pediculicidal ointment. The physicochemical properties of the ointment were characterized, and safety was determined using acute dermal irritation test (OECD 404), while the efficacy was assessed using an in vitro pediculicidal assay. Furthermore, the chemical compounds present in T. crispa were identified using liquid-liquid extraction followed by ultra-performance liquid chromatography quadruple time-of-flight mass spectrometric (UPLC-qTOF/MS) analysis. The community-based ointment formulation was light yellow in color, homogeneous, smooth, with distinct aromatic odor and pH of 6.92±0.09. It has spreadability value of 15.04±0.98 g·cm/sec and has thixotropic behavior. It was also found to be non-irritant, with a primary irritation index value of 0.15. Moreover, it was comparable to the pediculicidal activity of the positive control Kwell®, a commercially available 1% permethrin shampoo (P>0.05), and was significantly different to the activity of the negative control ointment, a mixture of palm oil and candle wax (P<0.05). These findings suggested that the community-based T. crispa pediculicidal ointment is safe and effective, having acceptable physicochemical characteristics. Its activity can be attributed to the presence of compounds moupinamide and physalin I.

Toxicidad aguda tópica e irritabilidad dérmica de la decocción de hojas de Piper auritum Kunth (caisimón de anís) / Acute topical toxicity and dermal irritability of decoction of Piper auritum Kunth (caisimón de anís)

Introducción: el Piper auritum Kunth comúnmente conocido como caisimón de anís, o anisón en algunas regiones del país, es una planta ampliamente utilizada como antiinflamatorio tópico. Tanto la hoja calentada como la decocción aplicada sobre la zona dañada son empleadas por la población con este fin. Objetivo: determinar la toxicidad aguda tópica y la irritabilidad dérmica primaria de la decocción al 50 por ciento de hojas frescas de Piper auritum. Métodos: se emplearon hojas frescas colectadas el mismo día del ensayo y se utilizaron las técnicas descritas en las guías de la Organización para la Cooperación Económica y el Desarrollo (OECD), la 434 para la toxicidad dérmica utilizando ratas Wistar, manteniendo la decocción por 24 horas en contacto con la piel previamente afeitada; el peso de los animales fue controlado antes, durante y al concluir el experimento. Y la OECD 404 para la irritabilidad tópica empleando conejos Nueva Zelanda aplicando el extracto por 4 horas a la zona rasurada. Resultados: no se apreciaron signos ni síntomas de toxicidad por la absorción dérmica en las ratas ni se observó evidencia de edema ni eritema en los conejos empleados. Conclusiones: la decocción al 50 por ciento de Piper auritum Kunth posee un índice de irritabilidad y una toxicidad dérmica bajas en nuestras condiciones de ensayo(AU)

Introduction: Piper auritum Kunth, commonly known as caisimón de anís or anisón in some regions of the country, is a plant widely used as topical anti-inflammatory. To this end, leaves may be warmed up and applied to the damaged area or a decoction prepared and drunk. Objective: determine the acute topical toxicity and primary dermal irritability of a 50 percent decoction of Piper auritum fresh leaves. Methods: fresh leaves collected on the same day of the assay were used to prepare a decoction, following the techniques described in Guideline 434 of the Organization for Economic Co-operation and Development (OECD 434) about dermal toxicity in Wistar rats. Decoction was kept in contact with previously shaved skin for 24 hours. The weight of animals was controlled before, during and upon completion of the experiment. OECD Guideline 404 was used for topical irritability in New Zealand rabbits, applying the extract to a previously shaved area for 4 hours. Results: no sign or symptom of toxicity due to dermal absorption was observed in the rats. Rabbits did not show any evidence of edema or erythema. Conclusions: Piper auritum Kunth 50 percent decoction has a low irritability and dermal toxicity rate in our test conditions(AU)

Toxicidad aguda tópica e irritabilidad dérmica de la decocción de hojas de Piper auritum Kunth (caisimón de anís) / Acute topical toxicity and dermal irritability of decoction of Piper auritum Kunth (caisimón de anís)

INTRODUCCIÓN: el Piper auritum Kunth comúnmente conocido como caisimón de anís, o anisón en algunas regiones del país, es una planta ampliamente utilizada como antiinflamatorio tópico. Tanto la hoja calentada como la decocción aplicada sobre la zona dañada son empleadas por la población con este fin. OBJETIVO: determinar la toxicidad aguda tópica y la irritabilidad dérmica primaria de la decocción al 50 % de hojas frescas de Piper auritum. MÉTODOS: se emplearon hojas frescas colectadas el mismo día del ensayo y se utilizaron las técnicas descritas en las guías de la Organización para la Cooperación Económica y el Desarrollo (OECD), la 434 para la toxicidad dérmica utilizando ratas Wistar, manteniendo la decocción por 24 horas en contacto con la piel previamente afeitada; el peso de los animales fue controlado antes, durante y al concluir el experimento. Y la OECD 404 para la irritabilidad tópica empleando conejos Nueva Zelanda aplicando el extracto por 4 horas a la zona rasurada. RESULTADOS: no se apreciaron signos ni síntomas de toxicidad por la absorción dérmica en las ratas ni se observó evidencia de edema ni eritema en los conejos empleados. CONCLUSIONES: la decocción al 50 % de Piper auritum Kunth posee un índice de irritabilidad y una toxicidad dérmica bajas en nuestras condiciones de ensayo.

INTRODUCTION: Piper auritum Kunth, commonly known as caisimón de anís or anisón in some regions of the country, is a plant widely used as topical anti-inflammatory. To this end, leaves may be warmed up and applied to the damaged area or a decoction prepared and drunk. OBJECTIVE: determine the acute topical toxicity and primary dermal irritability of a 50 % decoction of Piper auritum fresh LEAVES. METHODS: fresh leaves collected on the same day of the assay were used to prepare a decoction, following the techniques described in Guideline 434 of the Organization for Economic Co-operation and Development (OECD 434) about dermal toxicity in Wistar rats. Decoction was kept in contact with previously shaved skin for 24 hours. The weight of animals was controlled before, during and upon completion of the experiment. OECD Guideline 404 was used for topical irritability in New Zealand rabbits, applying the extract to a previously shaved area for 4 hours. RESULTS: no sign or symptom of toxicity due to dermal absorption was observed in the rats. Rabbits did not show any evidence of edema or erythema. CONCLUSIONS: Piper auritum Kunth 50 % decoction has a low irritability and dermal toxicity rate in our test conditions.