Benzofenon-4

EU 1223/2009 Annex VI — SCCS görüşü: Opinion on 2-Hydroxy-4-methoxybenzophenone-5-sulphonic acid

In Vitro Benzophenone-4 The ocular irritation potential of Benzophenone-4 was evaluated using the MatTek EpiOcular™ model, in accordance with OECD TG 492.7 The viability of normal human-derived keratinocytes in the 3-dimensional human tissue model following exposure to the test substance was determined via the MTT cytotoxicity assay. The 3-dimensional tissue construct models the corneal epithelium, with progressively stratified, but not cornified, cells. Tissues were exposed to Benzophenone-4 (solid, 50 mg) for ~ 6 h. The mean % tissue viability of Benzophenone-4 was determined to be 3.6%. Based on the results of this test, Benzophenone-4 was classified as irritating to the human eye. Benzophenone-8 An ocular irritation study on Benzophenone-8 was performed using the bovine corneal opacity and permeability test (OECD TG 437).8 Corneas from 3 animals were exposed to the test substance (20% w/v in paraffin oil; volume = 750 µl) for 4 h. The test substance was then removed from the front opening of the anterior chamber and the epithelium was rinsed. For the evaluation of corneal permeability, the passage of sodium fluorescein dye was measured using ultraviolet-visible (UV/Vis) spectrophotometry. Benzophenone-8 did not cause corneal opacity or permeability, resulting in a mean in vitro irritancy score of 1 after 4 h of exposure. Based on these results, the authors concluded that Benzophenone-8 was not a severe irritant or corrosive agent in the bovine corneal opacity and permeability test. Animal Benzophenones-1, -2, -3, -4, -6, -8, -9, -11, and -12 Most of the ocular irritation tests indicated that Benzophenones-1, -2, -3, -6, -9, -11, and -12 were non-irritating to the eyes of rabbits.1 Some studies indicated that Benzophenones-1, -2, and -4 were slightly to moderately irritating at 100% concentration; however, Benzophenones-1 and -2 were nonirritating when tested at 16% in dimethyl phthalate (DMP) or … [kırpıldı — bölüm toplam 3575 karakter]

Retrospective and Multicenter Studies Benzophenone-3 Over 3400 patients (age range: 3 to 96 years) with suspected allergic contact dermatitis were evaluated and then patch tested by 12 North American Contact Dermatitis Group dermatologists with a screening series of 50 allergens.136 The patients were patch tested (July 1, 1996 to June 30, 1998) using Finn chambers on Scanpor tape. The patches remained in place for 48 hours, and sites were evaluated initially at 48 to 72 h, and, again, between 72 and 168 h after initial placement. A positive allergic patch test result was generally interpreted as a 1+, 2+, or 3+ reaction manifested by erythematous papules, vesicles, or a spreading reaction with crust and ulceration. The relevance of the patch test reactions was determined in combination with the patient’s history and skin examination findings, and were integrated to determine the diagnostic group. Of the 4094 patients patch tested with 3% Benzophenone-3, 0.5% had allergic reactions (73.7% relevant reactions, i.e., definite, probable, or possible relevance to patient’s present dermatitis). A North American Contact Dermatitis Group (NACDG) study that was performed involved 5800 patients who were patch tested with Benzophenone-3 (3% in petrolatum).137 Patch testing was performed from July of 1998 to December of 2000. The patches remained in place for 48 h. Test sites were evaluated twice, initially at 48 h to 70 h and, again, at between 72 h and 178 h after initial placement. A positive allergic patch test result was interpreted to be a +, ++, or +++ reaction. Reactions of these types were manifested by erythematous papules, vesicles, or a spreading reaction with crust and ulceration. The incidence of positive reactions was 0.6%. The relevance of this incidence of positive reactions was classified as follows: 20.6% (definite relevance), 50% (possible relevance) and 2.9% (past relevance). … [kırpıldı — bölüm toplam 35692 karakter]

Dermal Penetration In Vitro Benzophenone-3 Sunscreen products were applied to excised human epidermis in Franz diffusion cells, with the amount penetrating into and across the epidermis assessed by high performance liquid chromatography (HPLC) for 8 h following application.22 All sunscreen agents investigated penetrated into the skin (0.25 g/m2 or 14% of applied dose). Only Benzophenone-3 penetrated human skin to the receptor phase (0.08 g/m2 or 10% of applied dose) after the 8-h study period. The penetration of Benzophenone-3 across excised human epidermis and high-density polyethylene (HDPE) membrane was measured using in vitro Franz-type diffusion cells.23 Human epidermal tissue (abdominal region of 1 female) was obtained by blunt dissection of full-thickness skin and heat separation. The tissue was mounted between the donor and receptor chambers of the diffusion cell, and the surface area available for diffusion was 1.18 cm2. The receptor chamber volume was 3.4 ml, and the receptor fluid was bovine serum albumin (4%) in phosphate-buffered saline. Both penetration and epidermal retention were measured following application of infinite and finite (epidermis only) doses of Benzophenone-3 (2%) in the following 5 vehicles: liquid paraffin (LP), coconut oil (CO), 50:50 ethanol:coconut oil (50:50 EC), aqueous cream (AC), and oily cream (OC). For the infinite dose studies, an aliquot (200 mg/cm2) of each formulation was applied to the epidermal surface under occlusion. For the finite dose studies, an aliquot of each formulation (20 mg/cm2) was applied without occlusion. Benzophenone-3 remaining in the epidermis (Rs, µg) was extracted twice with methanol and quantified using HPLC. The highest Benzophenone-3 skin retention was observed for the 50:50 EC combination. Maximal and minimal Benzophenone-3 fluxes were observed from liquid paraffin and coconut oil, respectively. … [kırpıldı — bölüm toplam 56296 karakter]

Acute Toxicity Studies Dermal Benzophenones-3, -4, -8, and -12 Benzophenones-3, -4, -8, and -12 were nontoxic when applied to the skin of rabbits at doses of > 5 g/kg.1 Benzophenone-3 A sunscreen formulation containing Benzophenone-3 (0.6% to 0.9%) was evaluated for dermal toxicity in a study involving 24 Wistar albino rats (12 males, 12 females).70 The study was performed in accordance with OECD TG 402. The formulation (2000 mg/kg) was applied to a 2" x 2", 4-ply gauze pad, and the patch was placed (secured with surgical tape) on hairless, dorsal skin. The patch remained in place for 24 h. Animals were observed for 14 d, after which the animals were killed. An untreated control group was also used. No overt signs of toxicity were observed during the 14-d observation period, and locomotor activity was normal. There were no statistically significant changes in terminal body weight between test and control animals. Hematological and serum biochemistry parameters were also normal. There were no abnormalities at necropsy or microscopic examination. The authors concluded that the acute dermal LD50 of the sunscreen formulation was greater than 2000 mg/kg in male and female rats. The same sunscreen formulation (0.6% to 0.9% Benzophenone-3) was applied to the skin of 6 male New Zealand rabbits, according to OECD TG 404.70 The formulation was applied to a 25 cm2 area of dorsal skin, using a 2" x 3", 4-ply gauze pad (secured with surgical tape). The application period was 72 h. Systemic toxicity was not observed. Benzophenone-12 The acute dermal toxicity of Benzophenone-12 was evaluated using 5 albino rabbits, in accordance with OECD TG 402.5 The test substance (aqueous paste; dose = 10,000 mg/kg) was applied, under an occlusive or semi-occlusive patch, for 24 h to the skin. Patch removal was followed by a 7-d observation period. None of the animal died, and no clinical signs or adverse findings were observed. The LD50 was > 10,000 mg/kg. Oral … [kırpıldı — bölüm toplam 18144 karakter]

In Vitro Benzophenone-3 The embryotoxicity of Benzophenone-3 was evaluated in the fish embryotoxicity test using zebrafish embryos.74 The test was performed in accordance with a modification of OECD TG 236. The applied number of zebrafish embryos was 40 at each concentration in 4 replicates. The experiment was prolonged until 120 h post-fertilization, because this period includes time points at which different developmental states can be observed. The following 6 concentrations of Benzophenone-3 (in dimethylsulfoxide (DMSO)) were prepared: 0.116 mM, 0.0789 mM, 0.0523 mM, 0.0307 mM, 0.0219 mM, and 0.00535 mM. Each solution was supplemented by a certain volume of DMSO in order to achieve the same DMSO concentration (3.52 mM; 250 µl/l). The positive control was 3,4-dichloroaniline (0.0247 mM), and water served as the negative control. DMSO served as the solvent control. The following endpoints were evaluated: mortality, malformations, hatching, and inflation of the swim bladder. Cumulative mortality was under 10% in the negative and solvent control groups at the end of the experiment. In the positive control group, cumulative mortality was 75%. In the negative and solvent control groups, the percentage of hatched embryos was 95%. No hatched embryos were observed in the positive control group. Except for one in the solvent control group (no swim bladder was observed), there were no malformations in the negative and solvent control groups. The following LC50 values were reported: 0.0766 mM (at 72 h post-fertilization), 0.0698 mM (at 96 h), and 0.0573 mM (at 120 h). At a concentration of 0.00438 mM, all embryos were able to inflate their swim bladder. However, at higher concentrations, Benzophenone-3 caused the absence of swim bladder inflation in a concentration-dependent manner. The calculated EC50 value was 0.0295 mM after 120 h post-fertilization. At 72 h post-fertilization, deformation of the tail was … [kırpıldı — bölüm toplam 23237 karakter]

EPA ToxValDB cilt/göz verisi — endpoint: skin sensitisation: in vivo (non-LLNA), sınıflandırma: Not likely to be sensitizing, tür: guinea pig, çalışma: skin sensitization, kılavuz: according to OECD Guideline 406 (Skin Sensitisation) according to EU Method B.6 (Skin Sensitisation) according to EPA OPP 81-6 (Skin Sensitisation), yıl: 1997. Sınır: bu bir derleme kayıttır; doz, tür ve maruziyet yolu birlikte değerlendirilmelidir.

EPA ToxCast ER modeli: östrojen reseptörü aktivitesi BULUNMADI (AUC agonist=0, antagonist=0). 18 in vitro deneyde test edildi. Sınır: in vitro tarama modelidir, doz/maruziyet bağlamı içermez; kozmetikteki kullanım seviyesinde insanda etki gösterdiği anlamına GELMEZ.