Dermal toxicity,eye and dermal irritation and skin sensitization evaluation of a new formulation of Bacillus thuringiensis var israelensis SH-14

Bacillus thuringiensis (Bt) is the best known and most widely used of all pesticidal microbes. The aim of this study was to assess the toxicity of a new formulation of Bacillus thuringiensis var israelensis SH-14 in rats through acute dermal toxicity, dermal and eye irritation experiments. The acute dermal toxicity and dermal and eye irritation studies were performed using rabbits according to the United States Environmental Protection Agency guidelines 885.3100, 870.2500 and 870.2500, respectively. The skin sensitization study was carried out in accordance to the EPA OPPTS 870.2600 using guinea pigs. There was no mortality and no evidence of treatment-related toxicity in acute dermal toxicity test. No dermal responses, including erythema/eschar or edema, were found in rabbits treated with the new formulation of Bti SH-14. Minimum response was observed after eye application of test substance. No skin sensitization reactions were observed after the challenge with the new formulation of Bti SH-14 in the Bti SH-14-treated guinea pigs. In summary, the present study demonstrated that the new formulation of Bti SH-14 is not acutely toxic via dermal route, has low eye irritation and would not cause dermal irritation or hypersensitivity to tested animals.     

Genotoxicity,acute oral and dermal toxicity,eye and dermal irritation and corrosion and skin sensitisation evaluation of silver nanoparticles

Abstract

To clarify the health risks related to silver nanoparticles (Ag-NPs), we evaluated the genotoxicity, acute oral and dermal toxicity, eye irritation, dermal irritation and corrosion and skin sensitisation of commercially manufactured Ag-NPs according to the OECD test guidelines and GLP. The Ag-NPs were not found to induce genotoxicity in a bacterial reverse mutation test and chromosomal aberration test, although some cytotoxicity was observed. In acute oral and dermal toxicity tests using rats, none of the rats showed any abnormal signs or mortality at a dose level of ～ 2000 mg/kg. Similarly, acute eye and dermal irritation and corrosion tests using rabbits revealed no significant clinical signs or mortality and no acute irritation or corrosion reaction for the eyes and skin. In a skin sensitisation test using guinea pigs, one animal (1/20) showed discrete or patchy erythema, thus Ag-NPs can be classified as a weak skin sensitiser.     

复方祛白喷雾剂的皮肤毒性和安全性研究

目的 研究复方祛白喷雾剂的皮肤毒性和经皮肤用药的安全性。方法 采用家兔急性皮肤毒性试验、豚鼠皮肤过敏试验、家兔皮肤刺激性试验,观察复方祛白喷雾剂经皮肤用药的急性毒性、过敏性和刺激性。结果 复方祛白喷雾剂对家兔完整皮肤与破损皮肤无急性毒性反应;对豚鼠皮肤无致敏作用;对家兔破损皮肤有轻度刺激性反应,但给药48 h后该刺激性反应消失。结论 复方祛白喷雾剂无明显急性皮肤毒性,经皮肤用药的安全性良好。     

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.     

Acute dermal toxicity of two quarternary organophosphonium salts in the rabbit

Tetrabutyl phosphonium chloride and tetrabutyl phosphonium bromide were evaluated for their potential to cause primary dermal irritation and acute dermal toxicity in rabbits. Both chemicals were found to not only be severely irritating to skin, but the pure hygroscopic chemicals caused death in more than half the number of rabbits used in the primary dermal irritation tests. Further investigations revealed the single-application dermal LD50 of tetrabutyl phosphonium chloride (Bu4PCl) (using an ethylene carbonate (EC) vehicle) was 600 mg/kg for male rabbits and 500 mg/kg for female rabbits. The single-application dermal LD50 of tetrabutyl phosphonium bromide (Bu4PBr) (using the EC vehicle) was 700 mg/kg for male rabbits and 850 mg/kg for female rabbits. The dermal LD50 of pure undiluted Bu4PCl was 225 mg/kg for male rabbits. These data indicate that Bu4PCl and Bu4PBr represent a substantial acute dermal toxicity hazard.     

Safety and toxicological evaluation of undenatured type II collagen

Previous research has shown that undenatured type II collagen is effective in the treatment of arthritis. The present study evaluated the broad-spectrum safety of UC-II by a variety of toxicological assays including acute oral, acute dermal, primary dermal irritation, and primary eye irritation toxicity. In addition, genotoxicity studies such as Ames bacterial reverse mutation assay and mouse lymphoma tests, as well as a dose-dependent 90-day sub-chronic toxicity study were conducted. Safety studies indicated that acute oral LD₅₀ of UC-II was greater than 5000?mg/kg in female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD₅₀ of UC-II was determined to be greater than 2000?mg/kg. Primary skin irritation tests conducted on New Zealand Albino rabbits classified UC-II as slightly irritating. Primary eye irritation tests conducted on rabbits indicated that UC-II was moderately irritating to the eye. UC-II did not induce mutagenicity in the bacterial reverse mutation test in five Salmonella typhimurium strains either with or without metabolic activation. Similarly, UC-II did not induce a mutagenic effect in the gene mutation test in mouse lymphoma cells either with or without metabolic activation. A dose-dependent 90-day sub-chronic toxicity study revealed no pathologically significant changes in selected organ weights individually or as percentages of body or brain weights. No significant changes were observed in hematology and clinical chemistry. Therefore, the results from the current study show a broad-spectrum safety profile of UC-II.     

伤必止的皮肤毒性实验研究

目的研究伤必止对动物皮肤的毒性作用。方法对健康家兔进行皮肤急性毒性实验、皮肤刺激性实验,对健康豚鼠进行皮肤过敏实验。结果伤必止对家兔完整及破损皮肤均未引起急性毒性反应和刺激反应,对豚鼠无致敏作用。结论伤必止应用于临床安全、无毒。     

The use of pH measurements to predict the potential of chemicals to cause acute dermal and ocular toxicity.

Regulatory guidelines for the assessment of acute dermal and ocular toxicity refer to the need to take the pH values of chemicals into consideration, since the acidic and basic properties of chemicals are known to play a role in the generation of acute dermal and ocular lesions. However, not all test guidelines provide an objective interpreting pH measurements in terms of acute skin or eye toxicity. The aim of this study was to develop classification models based on pH data for predicting the potential of chemicals to cause skin corrosion, skin irritation and eye irritation. The possible application of these models in the context of tiered testing strategies is discussed.     

Safety and toxicological evaluation of a novel chromium(III) dinicocysteinate complex

Chromium(III) is an essential trace element required for normal protein, fat and carbohydrate metabolism. It also helps in energy production and increasing lean body mass. Chromium(III) dinicocysteinate (CDNC) is a unique form of bioavailable chromium(III). This study was focused on determining the broad spectrum safety of CDNC. Acute oral, acute dermal, primary dermal and eye irritation studies, Ames’ bacterial reverse mutation assay, mammalian erythrocyte micronucleus test, and a 90-day dose-dependent oral toxicity study were conducted. Acute oral and dermal LD₅₀ of CDNC was found to be greater than 2000?mg/kg in Sprague-Dawley rats. A primary skin irritation study in New Zealand Albino rabbits demonstrated CDNC as slightly irritating. An eye irritation study exhibited that CDNC is moderately irritating. Ames’ bacterial reverse mutation assay and mammalian erythrocyte micronucleus test demonstrated CDNC as non-mutagenic. A dose-dependent 90-day oral toxicity study demonstrated no significant toxicity of CDNC. Body weight, food and water consumption, selected organ weights (expressed as percentages of body or brain weights), ocular health, hematology, blood chemistry, and histopathology showed no abnormal changes. Clinical and histopathological evaluation of CDNC identified a dose level of 5.7?mg/kg/day as the no observed adverse effect level (NOAEL). Overall, these results demonstrate the broad spectrum safety of CDNC.     

Ketoprofen: experimental overview of dermal toxicity

Ketoprofen (KP) is a widely used non-steroidal anti-inflammatory drug (NSAID). However, an increasing number of case reports suggest that in broad use, KP can cause allergic dermatitis. Most of these adverse effects have been attributed to the photoallergic potential of KP and photosensitivity. With the exception of a few reports in experimental animals, there is little evidence that KP actually causes dermal toxicity. In this study, in order to investigate the eventual underlying causes of KP dermal toxicity, we conducted primary irritation, skin cumulative, skin sensitization, phototoxicity and photosensitization tests in rodents and rabbits. Primary irritation and skin cumulative testing using New Zealand white rabbits revealed that application of KP (22, 15 and 10%) did not induce erythema or edema formation. Moreover, in skin sensitization and skin phototoxicity testing, using Hartley albino guinea pigs, there was no evidence of allergic or phototoxic potential. In the photosensitization test, KP induced skin reactions in six of eight guinea pigs with signs of erythema on the application site. Histologically, in photosensitized skin, epidermal hyperplasia, including incremental stratum granulosum, acanthosis, keratinocyte hypertrophy and dermal inflammatory cell infiltration, was observed. In this animal study, no primary irritation, cumulative irritation, skin sensitization or skin phototoxicity was observed with KP treatment. However, we identified photosensitization as the underlying cause of KP dermal toxicity.     

伤疡愈软膏皮肤毒性实验研究

目的 :考察伤疡愈软膏对动物皮肤的毒性作用。方法 :对健康家兔进行皮肤急性毒性实验、皮肤刺激性实验 ;对健康豚鼠进行皮肤过敏实验。结果 :伤疡愈软膏对家兔完整皮肤和破损皮肤均未引起急性毒性反应和刺激反应 ;对豚鼠完整皮肤无致敏作用。结论 :伤疡愈软膏用于临床安全、无毒。     

甲磺酸帕珠沙星搽剂皮肤用药安全性实验

目的：对甲磺酸帕珠沙星搽剂进行皮肤急性毒性试验、皮肤刺激性试验及皮肤过敏性试验,以考察其皮肤用药安全性。方法：将甲磺酸帕珠沙星搽剂涂抹于家兔背部完整或破损区脱毛皮肤,观察给药后动物局部皮肤红斑及水肿等急性毒性和刺激性情况。采用致敏与激发接触甲磺酸帕珠沙星搽剂,观察豚鼠过敏反应。结果：甲磺酸帕珠沙星搽剂对家兔完整或破损皮肤无明显局部毒性或局部刺激性。对豚鼠皮肤无过敏反应。结论：甲磺酸帕珠沙星搽剂短期皮肤用药是安全的。     

Safety and toxicological evaluation of AlgaeCal® (AC), a novel plant-based calcium supplement

The present study was conducted to examine the safety of a novel plant-based calcium supplement, derived from marine algae and containing high levels of calcium, magnesium, and other bone supporting minerals (commercially known as AlgaeCal^® (AC)). The present study evaluated the broad-spectrum safety of AC using a variety of toxicological assays including acute oral, acute dermal, primary skin irritation, and primary eye irritation toxicity. Under the conditions of the study, the acute oral LD₅₀ of AC was found to be greater than 5000?mg/kg body weight in rats, while the single acute dermal LD₅₀ was greater than 2000?mg/kg body weight. The primary skin irritation index of AC was found to be 0.4 and classified as slightly irritating to the skin. In primary eye irritation studies, the maximum mean total score of AC was observed to be 13.7 and classified as mildly irritating to the eye. Furthermore, another independent set of studies was conducted to obtain preliminary data for the teratogenic effects of AC in pregnant rats likely to arise from repeated gestational exposure, via oral gavage, over a test period of implantation through gestation (gestation days 5–19). Under the conditions of this pilot study, the effect of daily administration of AC by oral gavage at dose levels of 0, 500, 2500, and 5000?mg/kg/day during gestation days 5–19 of a 21-day pregnancy has appeared to result in no adverse toxicological effects to the pregnant rat or its developing offspring. A slight, non-significant increase in the incidence of incomplete sterna ossification (5^th center) was observed. Under the conditions of the study, a no-observed-adverse effect level (NOAEL) of 5000?mg/kg/day of AC during pregnancy of the rat was observed. Overall, no significant toxicities of AC were observed in these toxicity models. Therefore, the results from the current study demonstrate a broad-spectrum safety profile of AC.     

Assessment of skin and eye irritation of 14 products under the stepwise approach of the OECD

The determination of acute eye and skin irritation is included in international regulatory requirements for the testing of chemicals, because of the possibility of exposure during the production, transport, marketing, and disposal of products. Although there have been some advances in the areas of refinement and reduction, no single battery of tests has emerged as being acceptable as a complete replacement for the conventional Draize rabbit eye and skin irritation tests. Currently, dermal irritation and ocular irritation are generally evaluated in a sequential manner in the context of tiered assessment strategies. In this work, we show how 14 products, mostly designed to be used in agriculture, were evaluated in the Center of Experimental Toxicology of the Center for the Production of Laboratory Animals (Centro Nacional para la Producción de Animales de Laboratorio; CENPALAB) in order to assess their acute dermal and ocular effects. The performed studies include the acute dermal toxicity test, the acute dermal irritation/corrosion test, the hen's egg test-chorioallantoic membrane (HET-CAM) method, and the acute eye irritation/corrosion test. In general, it could be concluded that of the 14 products assessed, none of them showed systemic effects, but local reactions mainly to the eyes. The most significant effects were apparently related to the effects of azadirachtin, an active principle of 2 tested neem derivatives.     

消痤洁肤乳膏皮肤用药安全性实验研究

目的:评价消痤洁肤乳膏(含螺内酯和盐酸克林霉素)皮肤用药的安全性。方法:采用兔完整皮肤和破损皮肤分组涂布消痤洁肤乳膏和乳膏基质(每只1.0g)进行皮肤刺激实验(n=10);对豚鼠分组涂布消痤洁肤乳膏(每只0.2g)、乳膏基质(每只0.2g)、2,4-二硝基氯苯(每只0.2mL)进行皮肤致敏实验(n=50),2个实验均以红斑和水肿情况为评价指标;对大鼠分组涂布0.65、0.52、0.416g·kg-1的消痤洁肤乳膏和乳膏基质进行完整皮肤和破损皮肤的皮肤急性毒性实验(n=70),并设立对照组,观察各组大鼠7d内体质量变化、中毒反应及死亡情况。结果:消痤洁肤乳膏对兔完整皮肤及破损皮肤刺激强度、豚鼠致敏强度评分均为0,急性毒性实验中大鼠体质量变化无差异,未见死亡及中毒反应发生。结论:消痤洁肤乳膏是一种安全性较好的外用药。     

Toxicity studies with flutrimazole.

Studies with 1-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H- imidazole (flutrimazole, CAS 119006-77-8), a new topical imidazole antifungal agent, have been carried out to investigate the acute toxicity of the active substance in mice and rats, as well as the acute ocular and dermal irritation in rabbits, the dermal tolerance after repeated dose (21 days) applications in rabbits, and the sensitising, photoallergic and phototoxic potential in guinea pigs using 1% flutrimazole cream. LD50 values after oral or intraperitoneal administration were greater than or equal to 1000 mg/kg in both mice and rats, which reveal a very low acute toxicity of flutrimazole. No differences were found between the excipient and 1% flutrimazole cream in the acute ocular and dermal irritation studies in rabbits, the irritation indexes being indicative of no lesions due to flutrimazole. Cumulative dermal irritation studies in rabbits showed an improved local tolerance of a skin cream containing 1% flutrimazole as compared to a commercial skin cream containing 1% clotrimazole. The irritation indexes were 1.2 and 3.7, respectively (p less than 0.01). The corresponding histophatological findings confirmed the better local tolerance of 1% flutrimazole cream. Furthermore, it has been found that flutrimazole cream lacks sensitising potential (Magnusson and Kligman test), is also devoid of phototoxic potential and does not induce photoallergic reactions in guinea pigs, these data being confirmed by histopathological studies. These results, together with the very slight systemic absorption rate of flutrimazole from the 1% topical drug form, clearly show that no restrictions should be taken in the use of the cream for reasons of systemic toxicity or dermal tolerance.     

Safety and toxicological evaluation of Aflapin®: A novel Boswellia-derived anti-inflammatory product

Boswellia serrata gum resin has been used for treatment of various ailments in different cultures for thousands of years. Aflapin^® is a novel synergistic composition derived from B. serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. To assess the safety of Aflapin, a battery of acute and sub-acute toxicity studies were conducted in various animal models according to the OECD test guidelines. The acute oral LD50 of Aflapin was greater than 5000?mg/kg in female Sprague Dawley (SD) rats. Acute dermal LD50 of Aflapin was greater than 2000?mg/kg in SD rats. A primary dermal irritation study conducted using New Zealand White rabbits indicated that Aflapin is non-irritating to skin. Aflapin caused minimal ocular irritation in a primary eye irritation test conducted on New Zealand Albino rabbits. A repeat dose 28-day sub-acute oral toxicity study in SD rats demonstrated no significant signs of toxicity. Various evaluations including hematology, clinical chemistry, gross necropsy, and histopathology did not show any significant adverse changes. The NOAEL of Aflapin was found to be greater than 2500?mg/kg body weight. These studies demonstrate broad spectrum safety of Aflapin in animal models.     

Toxicological profile of diethyl phthalate: a vehicle for fragrance and cosmetic ingredients.

Diethyl phthalate (DEP; CAS No. 84-66-2) has many industrial uses, as a solvent and vehicle for fragrance and cosmetic ingredients and subsequent skin contact. This review focuses on its safety in use as a solvent and vehicle for fragrance and cosmetic ingredients. Available data are reviewed for acute toxicity, eye irritation, dermal irritation, dermal sensitization, phototoxicity, photoallergenicity, percutaneous absorption, kinetics, metabolism, subchronic toxicity, teratogenicity, reproductive toxicity, estrogenic potential, genetic toxicity, chronic toxicity, carcinogenicity, in vitro toxicity, ecotoxicity, environmental fate and potential human exposure. No toxicological endpoints of concern have been identified. Comparison of estimated exposure (0.73 mg/kg/day) from dermal applications of fragrances and cosmetic products with other accepted industrial (5 mg/m(3) in air) and consumer exposures (350 mg/l in water; 0.75 mg/kg/day oral exposure) indicates no significant toxic liability for the use of DEP in fragrances and cosmetic products.     

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. Copyright © 2013 John Wiley & Sons, Ltd.     

双氯芬酸二乙胺盐凝胶皮肤毒性实验

目的观察双氯芬酸二乙胺盐凝胶经皮用药的安全性。方法对家兔进行皮肤急性毒性实验、皮肤刺激性实验；对豚鼠进行皮肤变态反应实验。结果双氯芬酸二乙胺盐凝胶均未引起家兔毒性反应；对家兔完整皮肤无刺激作用，但对破损皮肤有轻度刺激作用；对豚鼠皮肤无致变态反应作用。结论双氯芬酸二乙胺盐凝胶经皮给药安全。