ETHYL HEXYL DIMETHYL PABA (ETL HEKZL DMETL PABA)
ETHYLHEXYL DIMETHYL PABA
ETHYLHEXYL DIMETHYL PABA; ethylhexyl dimethyl paba; ethyl hexyl dimethyl paba; ethyl hexyl dmethyl paba; Padimate O Octyl dimethyl p-aminobenzoate; Octyl dimethyl PABA 2-Ethylhexyl p-(dimethylamino)benzoate OD-PABA; arlatone UVB; benzoic acid, 4-(dimethylamino)-, 2-ethylhexyl ester; benzoic acid, p-(dimethylamino)-, 2-ethylhexyl ester; escalol 507; 2-ethyl hexyl 4-(dimethyl amino) benzoate; 2-ethylhexyl 4-(dimethylamino)benzoate; 2-ethylhexyl p-(dimethylamino)benzoate; 2-ethylhexyl p-dimethylaminobenzoate; eusolex 6007; octyl dimethyl p-aminobenzoate; octyl dimethyl paba; padimate O; Octyl Dimethyl PABA; T/N: Unichem EHD; T/N: Escalol 507; TN: Padimate O; Ethylhexyl Dimethyl PABA; Benzoic Acid, 4( Dimethylamino )-, 2-Ethylhexyl Ester; Benzoic acid, 4-(dimethylamino)-, 2-ethylhexyl ester; Padimate O; 4-Dimethylaminobenzoic acid, ethylhexyl ester; p-Dimethylaminobenzoic acid 2-ethylhexyl ester; Octyl dimethyl p-aminobenzoate; Octyl-p-(dimethylamino) benzoate Padimate O; 2-Ethylhexyl p-dimethylaminobenzoate; Eusolex 6007; 4-(Dimethylamino)benzoic acid 2-ethylhexyl ester; Arlatone UVB; Escalol 507; 2-Ethylhexyl-4 (dimethylamino) benzoate; 2-Ethylhexyl p-(dimethylamino)benzoate; Octyl dimethyl PABA
Ethylhexyl dimethyl para-aminobenzoic acid (PABA) is an oily yellow liquid derivative of water-soluble PABA commonly used in sunscreen. Ethylhexyl dimethyl PABA is widely used as an ingredient in many cosmetics at an average concentration of 1.25% (0.5-2.0%) in Korea. Previous studies, including those involving animals, have demonstrated that ethylhexyl dimethyl PABA is toxic to the following four organs: testis, epididymis, spleen, and liver. In addition, experiments using human keratinocytes found that ethylhexyl dimethyl PABA inhibits cell growth and DNA synthesis at low concentrations, and halted the cell cycle of MM96L cells (human melanoma cell line) at the G1 phase. Despite limited clinical data in humans, many studies have confirmed increased mutagenicity of ethylhexyl dimethyl PABA following exposure to sunlight, which suggests that this molecule is likely to contribute to onset of sun-induced cancer despite protecting the skin through absorption of UVB. For risk assessment, the no observed adverse effect level (NOAEL) chosen was 100 mg/kg bw/day in a 4 weeks oral toxicity study. Systemic exposure dosage (SED) was 0.588 mg/kg bw/day for maximum use of ethylhexyl dimethyl PABA in cosmetics. Based on the risk assessment and exposure scenarios conducted in this study, the margin of safety (MOS) was calculated to be 180.18 for a sunscreen containing 8% ethylhexyl dimethyl PABA, which is the maximum level allowed by the relevant domestic authorities.
Keywords: Ethylhexyl dimethyl PABA, Cosmetics, Sunscreen, Risk assessment, Toxicity
INTRODUCTION OF ETHYLHEXYL DIMETHYL PABA
Ethylhexyl dimethyl PABA (CAS No. 21245-02-3) is an organic derivative of water-soluble PABA (4-aminobenzoic acid) included in sunscreen and other cosmetics. It is a yellow water-insoluble oily liquid with an ester bond formed by condensation of 2-ethylhexanol and dimethylaminobenzoic acid (Fig. 1). Ethylhexyl dimethyl PABA is also known as padimate O, OD-PABA, or octyl dimethyl p-aminobenzoate (Table 1). The Ministry of Food and Drug Safety (MFDS) and US Food and Drug Administration (FDA) mandate that its concentration in any cosmetic product shall not exceed 8% (1). Previous animal studies showed that high concentrations of ethylhexyl dimethyl PABA may be toxic to the epididymis and caution should be exercised when administering this substance to infants younger than six months of age due lack of understanding of its metabolism and absorption (2). Previous risk assessment data for ethylhexyl dimethyl PABA includes potential toxicity data and national and international regulations only. The present study summarizes a risk assessment that included determination of the margin of safety (MOS) at concentrations in cosmetics allowed by domestic authorities, a summary of existing experimental toxicity data, and exposure data associated with the amount of use in domestic cosmetic products.
PHYSICAL AND CHEMICAL PROPERTIES OF ETHYLHEXYL DIMEHYL PABA
The range of purities of ethylhexyl dimethyl PABA used as a raw material for cosmetics is approximately 98-99.5%. It is an oily yellow liquid state with oil characteristics. It has a molecular weight of 277.4053. It is soluble in alcohol, and strong acid and base, but is insoluble in water and acetic acid.
Chemico-physical properties of ethylhexyl dimethyl PABA
Physical property; Yellow liquid with oil characteristics
Molecular weight; 277.4053
PKa; 6.027
Boiling point; 387.8°C at 760 mmHg
Melting point; 242.5-243.5°C
Ignition point; 124.1°C
Steam pressure; 7.7 × 107 mmHg at 25°C
Specific gravity; 0.99
Solubility; Dissolved in alcohol, HCl, KOH
Not dissolved in acetic acid
Dissolved in water at 25°C if 5.3 × 103 mg/L
Density; 1.0 ± 0.1 g/cm3
COSMETIC USE
Ethylhexyl dimethyl PABA is used in sunscreen and in a variety of beauty products. According to the Environmental Working Group (EWG) database, it is used in many products including lipstick, conditioner, shampoo, anti-aging agents, hair spray, and sunscreen. Use of ethylhexyl dimethyl PABA in non-cosmetic products has not been reported in Korea. According to a survey conducted by the MFDS the average concentration of ethylhexyl dimethyl PABA in cosmetic products is 1.25% (ranging from 0.5-2.0%).
HAZARD IDENTIFICATION OF ETHYLHXYL DIMETHYL PABA
Single and repeated dose toxicity studies of ethylhexyl dimethyl PABA have identified various toxicities including skin irritation, reproductive toxicity, genotoxicity, and phototoxicity. Repeated dosing of experimental animals resulted in organ toxicity and organ pigmentation. The major proposed mechanism of ethylhexyl dimethyl PABA toxicity is DNA damage by light-modified ethylhexyl dimethyl PABA.
General toxicity
In an acute toxicity study of ethylhexyl dimethyl PABA, the LD50 in rats was 14,900 mg/kg (3) and no irritation was observed in a human patch test using white Vaseline® mixed with 8% ethylhexyl dimethyl PABA.
According to a report by the Scientific Committee on Cosmetology (SCC) (1999) (4), a 4-week oral administration study was conducted in rats in accordance with GLP principles. Ethylhexyl dimethyl PABA was administered orally (by gavage) at doses of 0, 100, 300, and 1,000 mg/kg/day (Groups 1, 2, 3, and 4, respectively) to 10 male and female rats per group. An additional 5 male and 5 female rats were added to Groups 1 and 4 to evaluate the convalescence stage. No clinical symptoms were observed except salivation in Group 4 and decreased weight in Group 4 three to four weeks after administration, which did not normalize following the convalescence period. Gross inspections during autopsies of the animals found that the capsule of the spleen was severely degraded in one female in Group 4. A male in Group 4 (4/10) exhibited a softened testis and 8 males exhibited reduced testis size. No prostate, epididymis, or seminal vesicle abnormalities were observed. Three out of the five males in the Group 4 convalescence group exhibited reduced testis size. A female rat in Group 4 showed increased spleen weight, and the females in Groups 3 and 4 exhibited increased liver weight. Furthermore, the males in Group 4 exhibited liver weight gain and pituitary gland weight loss. Among the animals in the convalescence group, the males in Group 4 exhibited kidney weight gain, but showed no changes in testis or pituitary gland weights. Histopathological examinations showed moderate or moderately severe testicular atrophy in all males in Group 4 and epididymal edema in seven out of the ten males in Group 4. All males in Group 4 had spleen pigmentation, but spleen pigmentation was more conspicuous in the females in Group 3 and was extensive in the females in Group 4. The NOAEL was determined at 100 mg/kg/day based on pigmentation of the spleen (5). The SCC determined that this NOAEL may have been too conservative, so a NOAEL value of 300 mg/kg/day was assigned to ethylhexyl dimethyl PABA.
No toxicity was observed in 20 rabbits administered 140 or 280 mg/kg/day of ethylhexyl dimethyl PABA for 13 weeks.
Reproductive and developmental toxicity of Ethylhexyl Dimethyl PABA
When 2 mL/kg daily ethylhexyl dimethyl PABA was applied to the skin of rats at 6 to 16 days of pregnancy, wavy ribs were observed on both sides of 7/56 fetuses and on one side of 2/56 fetuses. However, these observations were not attributed to ethylhexyl dimethyl PABA toxicity, as the rat species used in this study commonly exhibit wavy ribs.
According to a report by Erol et al. , dermal exposure to OD-PABA did not affect pubertal development or thyroid function in female or male rats. As such, OD-PABA was not classified as an endocrine disrupting chemical.
Mutagenicity/Genotoxicity
In vivo micronucleus testing was conducted on mice to evaluate mutagenesis. Ethylhexyl dimethyl PABA (5,000 mg/kg) was intraperitoneally injected into three groups of mice (n = 10 mice per group; 30, 48, or 72 hr), resulting in no mutagenesis .
A chromosomal aberration test was performed in human lymphocytes. This assay is based on metabolic activation in response to the S9 mix. Ethylhexyl dimethyl PABA was dissolved in ethanol at concentrations of 315 to 5,010 μg/mL. No chromosomal aberrations were observed .
Carcinogenicity
Ethylhexyl dimethyl PABA is not considered carcinogenic per International Agency for Research on Cancer (IARC), Association Advancing Occupational and Environmental Health (ACGIH), US National Toxicology Program (NTP), and Occupational Safety and Health Administration (OSHA) .
Ocular irritation
Two percent ethylhexyl dimethyl PABA mixed with mineral oil was applied to the eyes of rabbits. No irritation was reported when both eyes are washed and left unattended. A slight irritation was observed in rabbit mucous membranes during a Draize test with 2% and 5% ethylhexyl dimethyl PABA in mineral oil.
Skin irritation
Five percent ethylhexyl dimethyl PABA mixed with mineral oil applied to rabbit skin did not cause irritation (3,8). In addition, a patch containing ethylhexyl dimethyl PABA dissolved in 4% white Vaseline® affixed to adult volunteers did not cause skin sensitization . No irritation was observed following application of 5% ethylhexyl dimethyl PABA to normal and damaged rabbit skin for 24 hr . A human patch test study showed no incidence of irritation following application of yellow soft paraffin with 5% ethylhexyl dimethyl PABA for 48 hr. When 1 mg/mL of estradiol was prescribed during the autumn and winter seasons to postmenopausal women (4 persons), women receiving hormone replacement therapy, women with sensitivity to ethylhexyl dimethyl PABA, women with epilepsy, or women prescribed medications to control liver metabolism (aged between 54 and 63, body weight between 67 and 93 kg) along with ethylhexyl dimethyl PABA applied to their arm over a 10 cm2 area, daily for nine days, no skin irritation was observed.
Skin sensitization
Five percent ethylhexyl dimethyl PABA in mineral oil did not cause skin sensitization in guinea pigs. In addition, 50 μL of 0.1% ethylhexyl dimethyl PABA in saline was injected into ten guinea pigs, followed by nine additional 0.1 mL injections administered across three weeks. The guinea pigs did not exhibit sensitization when challenged with a 0.05 mL dose after a 12-week resting phase. No skin sensitization was observed in humans following application of 1.5% or 4% ethylhexyl dimethyl PABA mixed with white Vaseline. Furthermore, 15 volunteers were instructed to apply soft paraffin containing 4% ethylhexyl dimethyl PABA for three weeks, followed by a challenge application after a two week rest phase, after which no skin sensitization was observed. Consistent with this result, 150 individuals subjected to a patch test with 7% ethylhexyl dimethyl PABA with 3% oxybenzone did not exhibit skin sensitization. Another study showed that application of soft paraffin containing 7% ethylhexyl dimethyl PABA to 156 individuals did not cause sensitization. Finally, a slight stinging reaction was reported during the induction period when a mixture of 3% benzophenone and 8% ethylhexyl dimethyl PABA was applied to 90 individuals, but no skin sensitization was observed. Toxicokinetics To determine whether a new metered-dose topical aerosol (MDTA) medication containing ethylhexyl dimethyl PABA as a skin penetration enhancer could enhance transdermal delivery of estradiol, estradiol MDTA containing ethylhexyl dimethyl PABA was applied to the abdomens of postmenopausal women for nine days and the levels of estradiol and estrone in the blood were measured daily via radioimmunoassay. Following MDTA treatment, 1 mg of estradiol sprayed onto three adjacent areas of skin (10 cm2) on the abdomens of each subject did not induce skin irritation. Blood estradiol concentrations were measured in four women (aged between 54 and 63 years, body weight between 67 and 93 kg). The average blood estradiol concentration was 53 pg/mL across the 9-day study period, which was significantly greater than the reference value of 13 pg/mL. (p < 0.001). This test confirmed that the MDTA containing ethylhexyl dimethyl PABA enhanced transdermal delivery of estradiol. 14C-labelled ethylhexyl dimethyl PABA in ethanol was applied to 100 cm2 of the forearms of each of four male and female subjects. The forearms were then covered with gauze for 24 hr after the ethanol completely evaporated. Blood was collected after 0, 2, 4, 8, 24, and 72 hr and urine was collected for 24 hr. No radioactivity was found in the blood samples while 2.45% and 1.18% radioactivity were found in the urine samples of the male and female subjects, respectively (average % of total radioactivity). The average radioactivity recovered after washing the skin at the application site was 95.7%. Assuming that 0.5 mg/cm2 was applied at a concentration of 8% to 1.8 m2, the total amount absorbed was 13 mg, or 0.2 mg/kg. An oil-in-water emulsion lotion was used for an in vitro percutaneous penetration test, and guinea pig and human skin were used as the membranes. HEPES-buffered Hank’s balanced salt solution containing gentamycin sulfate and bovine serum albumin was used as the aqueous solution in the receiving chamber. The total absorption rate of ethylhexyl dimethyl PABA transferred to the receiving chamber and the skin was 12.7 ± 2.5%. Evaluation of ethylhexyl dimethyl PABA metabolism was also included in this test. Guinea pig skin hydrolyzed approximately 13-35% of ethylhexyl dimethyl PABA transferred to the aqueous solution through esterase activity, while human skin hydrolyzed 37% of ethylhexyl dimethyl PABA. The value used for skin absorption in humans for the risk assessment was 2.45% based on the limited skin absorption data.
Etilheksil dimetil para-aminobenzoik asit (PABA), güne koruyucusunda yaygn olarak kullanlan, suda çözünür PABA’nn yal sar bir sv türevidir. Etilheksil dimetil PABA, Kore’de ortalama% 1,25 (% 0,5-2,0) konsantrasyonda birçok kozmetikte içerik olarak yaygn ekilde kullanlmaktadr. Hayvanlar içerenler de dahil olmak üzere önceki çalmalar, etilheksil dimetil PABA’nn u dört organ için toksik olduunu göstermitir: testis, epididim, dalak ve karacier. Ek olarak, insan keratinositlerini kullanan deneyler, etilheksil dimetil PABA’nn düük konsantrasyonlarda hücre büyümesini ve DNA sentezini inhibe ettiini ve G1 faznda MM96L hücrelerinin (insan melanom hücre hatt) hücre döngüsünü durdurduunu buldu. nsanlarda snrl klinik verilere ramen, birçok çalma, güne na maruz kalmann ardndan etilheksil dimetil PABA’nn artm mutajenisitesini dorulamtr; bu da, bu molekülün, cildi UVB’nin emilmesi yoluyla korumasna ramen, günein neden olduu kanserin balamasna katkda bulunacan düündürmektedir. Risk deerlendirmesi için, 4 haftalk bir oral toksisite çalmasnda seçilen advers etki gözlenmeyen seviye (NOAEL) 100 mg / kg canl arlk / gün’dür. Kozmetiklerde etilheksil dimetil PABA’nn maksimum kullanm için sistemik maruziyet dozu (SED) 0.588 mg / kg canl arlk / gün’dür. Bu çalmada gerçekletirilen risk deerlendirmesi ve maruziyet senaryolarna göre, ilgili yerel makamlarca izin verilen maksimum düzey olan% 8 etilheksil dimetil PABA içeren bir güne koruyucu için güvenlik marj (MOS) 180,18 olarak hesaplanmtr.
Anahtar Kelimeler: Etilheksil dimetil PABA, Kozmetik, Güne kremi, Risk deerlendirmesi, Toksisite
ETLHEKSL DMETL PABA’NIN GR
Etilheksil dimetil PABA (CAS No. 21245-02-3), güne kremi ve dier kozmetiklerde bulunan suda çözünür PABA’nn (4-aminobenzoik asit) organik bir türevidir. 2-etilheksanol ve dimetilaminobenzoik asidin younlamasyla oluan ester bana sahip sar suda çözünmeyen yal bir svdr (ekil 1). Etilheksil dimetil PABA, padimat O, OD-PABA veya oktil dimetil p-aminobenzoat olarak da bilinir (Tablo 1). Gda ve laç Güvenlii Bakanl (MFDS) ve ABD Gda ve laç Dairesi (FDA) herhangi bir kozmetik üründeki konsantrasyonunun% 8’i (1) geçmemesini zorunlu klar. Önceki hayvan çalmalar, yüksek etilheksil dimetil PABA konsantrasyonlarnn epididim için toksik olabileceini ve bu maddeyi alt aylktan küçük bebeklere uygularken, metabolizmas ve absorpsiyonunun anlalamamas nedeniyle dikkatli olunmas gerektiini göstermitir (2). Etilheksil dimetil PABA için önceki risk deerlendirme verileri potansiyel toksisite verilerini ve yalnzca ulusal ve uluslararas düzenlemeleri içerir. Bu çalma, yerel otoriteler tarafndan izin verilen kozmetik konsantrasyonlarnda güvenlik marjnn (MOS) belirlenmesini, mevcut deneysel toksisite verilerinin bir özetini ve ev içi kozmetik ürünlerdeki kullanm miktar ile ilikili maruz kalma verilerini içeren bir risk deerlendirmesini özetlemektedir.
ETLHEKSL DMEL PABA’NIN FZKSEL VE KMYASAL ÖZELLKLER
Kozmetikler için hammadde olarak kullanlan etilheksil dimetil PABA’nn saflk aral yaklak% 98-99,5’tir. Ya özellii olan yal sar bir sv haldir. 277.4053 moleküler arla sahiptir. Alkolde ve kuvvetli asit ve bazda çözünür, ancak su ve asetik asitte çözünmez.
Etilheksil dimetil PABA’nn kimyasal-fiziksel özellikleri
Fiziksel özellik; Ya özellikli sar sv
Moleküler arlk; 277.4053
PKa; 6.027
Kaynama noktas; 760 mmHg’de 387,8 ° C
Erime noktas; 242,5-243,5 ° C
Ateleme noktas; 124.1 ° C
Buhar basnc; 25 ° C’de 7,7 × 107 mmHg
Spesifik yer çekimi; 0,99
Çözünürlük; Alkol, HCl, KOH içinde çözüldü
Asetik asitte çözünmez
5,3 × 103 mg / L ise 25 ° C’de suda çözülür
Younluk; 1,0 ± 0,1 g / cm3
KOZMETK KULLANIM
Etilheksil dimetil PABA, güne kreminde ve çeitli güzellik ürünlerinde kullanlr. Çevresel Çalma Grubu (EWG) veri tabanna göre ruj, saç kremi, ampuan, yalanmay geciktirici maddeler, saç spreyi ve güne kremi gibi birçok üründe kullanlmaktadr. Etilheksil dimetil PABA’nn kozmetik olmayan ürünlerde kullanm Kore’de bildirilmemitir. MFDS tarafndan yaplan bir aratrmaya göre kozmetik ürünlerdeki ortalama etilheksil dimetil PABA konsantrasyonu% 1,25’tir (% 0,5-2,0 arasnda).
ETYLHXYL DIMETHYL PABA’NIN TEHLKE TANIMI
Etilheksil dimetil PABA’nn tek ve tekrarlanan doz toksisite çalmalar, cilt tahrii, üreme toksisitesi, genotoksisite ve fototoksisite dahil olmak üzere çeitli toksisiteler belirlemitir. Deney hayvanlarnn tekrarlanan dozlar, organ toksisitesi ve organ pigmentasyonu ile sonuçland. Etilheksil dimetil PABA toksisitesinin önerilen balca mekanizmas, kla modifiye edilmi etilheksil dimetil PABA’nn neden olduu DNA hasardr.
Genel toksisite
Etilheksil dimetil PABA’nn akut toksisite çalmasnda, sçanlardaki LD50 14.900 mg / kg’dr (3) ve% 8 etilheksil dimetil PABA ile kartrlm beyaz Vaseline® kullanlarak yaplan bir insan yama testinde tahri gözlenmemitir.
Bilimsel Kozmetoloji Komitesi (SCC) (1999) (4) tarafndan hazrlanan bir rapora göre, GLP ilkelerine uygun olarak sçanlarda 4 haftalk bir oral uygulama çalmas yaplmtr. Etilheksil dimetil PABA, grup bana 10 erkek ve dii sçana 0, 100, 300 ve 1,000 mg / kg / gün dozlarnda (srasyla Gruplar 1, 2, 3 ve 4) oral yoldan (gavaj yoluyla) uyguland. yileme aamasn deerlendirmek için Grup 1 ve 4’e ek bir 5 erkek ve 5 dii sçan eklendi. Grup 4’te tükürük salgs dnda hiçbir klinik semptom gözlenmedi ve Grup 4’te uygulamadan üç ila dört hafta sonra kilo azald, bu iyileme dönemini takiben normale dönmedi. Hayvanlarn otopsileri srasnda yaplan kapsaml incelemeler, dalak kapsülünün Grup 4’teki bir kadnda ciddi ekilde bozulmu olduunu buldu. Grup 4’teki (4/10) bir erkek, yumuatlm bir testis sergiledi ve 8 erkek, testis boyutu küçültüldü. Prostat, epididim veya seminal vezikül anormallikleri gözlenmedi. 4. Grup nekahat grubundaki be erkekten üçünde testis boyutu küçüldü. Grup 4’teki bir dii sçan, artan dalak arl gösterdi ve Grup 3 ve 4’teki diiler, artm karacier arl sergiledi. Ayrca, Grup 4’teki erkekler karacier kilo alm ve hipofiz bezi kilo kayb gösterdi. yileme grubundaki hayvanlar arasnda, Grup 4’teki erkekler böbrek arl art sergilediler, ancak testis veya hipofiz bezi arlklarnda hiçbir deiiklik göstermedi. Histopatolojik incelemeler Grup 4’teki tüm erkeklerde orta veya orta derecede iddetli testis atrofisi ve Grup 4’teki on erkekten yedisinde epididimal ödem gösterdi. Grup 4’teki tüm erkeklerde dalak pigmentasyonu vard, ancak Grup 3’teki kadnlarda dalak pigmentasyonu daha belirgindi. Grup 4’teki kadnlarda yaygnd. NOAEL dalak pigmentasyonuna göre 100 mg / kg / gün olarak belirlendi (5). SCC, bu NOAEL’in çok muhafazakar olabileceini belirledi, bu nedenle 300 mg / kg / gün NOAEL deeri etilheksil dimetil PABA’ya atand. 13 hafta boyunca 140 veya 280 mg / kg / gün etilheksil dimetil PABA uygulanan 20 tavanda hiçbir toksisite gözlenmemitir.
Ethylhexyl Dimethyl PABA’nn üreme ve geliimsel toksisitesi
Gebeliin 6-16. Gününde sçanlarn derisine günlük 2 mL / kg etilheksil dimetil PABA uygulandnda, 7/56 fetüsün her iki tarafnda ve 2/56 fetüsün bir tarafnda dalgal kaburgalar görüldü. Bununla birlikte, bu çalmada kullanlan sçan türleri yaygn olarak dalgal kaburgalar sergilediinden, bu gözlemler etilheksil dimetil PABA toksisitesine atfedilmemitir.
Erol ve ark. OD-PABA’ya dermal maruziyet dii veya erkek sçanlarda pubertal geliimi veya tiroid fonksiyonunu etkilememitir. Bu nedenle OD-PABA, bir endokrin bozucu kimyasal olarak snflandrlmamtr.
Mutajenite / Genotoksisite
n vivo mikronükleus testi, mutajenezin deerlendirilmesi için fareler üzerinde gerçekletirildi. Etilheksil dimetil PABA (5,000 mg / kg) intraperitoneal olarak üç fare grubuna (grup bana n = 10 fare; 30, 48 veya 72 saat) enjekte edilerek mutajenez olmamtr.
nsan lenfositlerinde bir kromozomal aberasyon testi yapld. Bu test, S9 karmna yant olarak metabolik aktivasyona dayanmaktadr. Etilheksil dimetil PABA, 315 ila 5.010 ug / mL’lik konsantrasyonlarda etanol içerisinde çözündürüldü. Hiçbir kromozomal sapma gözlenmedi.
Kanserojenlik
Etilheksil dimetil PABA, Uluslararas Kanser Aratrma Ajans (IARC), Mesleki ve Çevre Sal Gelitirme Dernei (ACGIH), ABD Ulusal Toksikoloji Program (NTP) ve Mesleki Güvenlik ve Salk daresi (OSHA) bana kanserojen olarak kabul edilmemektedir.
Göz tahrii
Tavanlarn gözlerine mineral ya ile kartrlm yüzde iki etilheksil dimetil PABA uyguland. Her iki göz ykandnda ve gözetimsiz brakldnda herhangi bir tahri bildirilmedi. Mineral ya içinde% 2 ve% 5 etilheksil dimetil PABA ile bir Draize testi srasnda tavan mukoza zarlarnda hafif bir tahri gözlendi.
Cilt tahrii
Tavan derisine uygulanan mineral ya ile kartrlan yüzde be etilheksil dimetil PABA tahrie neden olmad (3,8). Ek olarak, yetikin gönüllülere yaptrlm% 4 beyaz Vazelin® içinde çözülmü etilheksil dimetil PABA içeren bir yama ciltte hassasiyete neden olmad. 24 saat boyunca normal ve hasarl tavan derisine% 5 etilheksil dimetil PABA uygulanmasnn ardndan hiçbir tahri gözlenmedi. Bir insan yama testi çalmas, 48 saat boyunca% 5 etilheksil dimetil PABA ile sar yumuak parafin uygulamasnn ardndan hiçbir tahri vakas göstermedi. Sonbahar ve k mevsimlerinde menopoz sonras kadnlara (4 kii) 1 mg / mL estradiol reçete edildiinde, hormon replasman tedavisi alan kadnlara, etilheksil dimetil PABA’ya duyarl kadnlara, epilepsili kadnlara veya kadnlara karacier metabolizmasn kontrol etmek için ilaçlar reçete edildiinde 54 ile 63 yalar arasnda, vücut arl 67 ile 93 kg arasnda) ve kollarna 10 cm2’lik bir alan üzerinde her gün dokuz gün süreyle uygulanan etilheksil dimetil PABA ile birlikte cilt tahrii gözlenmedi. Cilt hassasiyeti
Mineral yadaki yüzde be etilheksil dimetil PABA, kobaylarda cilt hassasiyetine neden olmamtr. Ek olarak, salin içinde 50 uL% 0.1 etilheksil dimetil PABA on kobay içine enjekte edildi, ardndan üç hafta boyunca dokuz ek 0.1 mL enjeksiyon uyguland. Gine domuzlar, 12 haftalk bir dinlenme aamasndan sonra 0.05 mL’lik bir dozla tehdit edildiinde duyarllk göstermedi. Beyaz Vazelin ile kartrlm% 1.5 veya% 4 etilheksil dimetil PABA uygulamasnn ardndan insanlarda cilt hassaslamas gözlenmedi. Ayrca, 15 gönüllüye üç hafta boyunca% 4 etilheksil dimetil PABA içeren yumuak parafin uygulamas, ardndan iki haftalk dinlenme aamasndan sonra bir meydan okuma uygulamas talimat verildi, ardndan cilt hassaslamas gözlenmedi. Bu sonuçla tutarl olarak,% 3 oksibenzon içeren% 7 etilheksil dimetil PABA ile bir yama testine tabi tutulan 150 kii, cilt hassasiyeti göstermedi. Baka bir çalma,% 7 etilheksil dimetil PABA içeren yumuak parafinin 156 kiiye uygulanmasnn duyarllamaya neden olmadn gösterdi. Son olarak, 90 kiiye% 3 benzofenon ve% 8 etilheksil dimetil PABA karm uygulandnda indüksiyon periyodu srasnda hafif bir batma reaksiyonu bildirildi, ancak cilt hassaslamas gözlenmedi. Toksikokinetik Bir cilt penetrasyon artrc olarak etilheksil dimetil PABA içeren yeni bir ölçülü doz topikal aerosol (MDTA) ilacnn estradiolün transdermal datmn artrp artrmayacan belirlemek için, postmenopozal kadnlarn karnlarna dokuz gün süreyle etilheksil dimetil PABA içeren estradiol MDTA uyguland ve kandaki estradiol ve estron seviyeleri radyoimünoassay ile günlük olarak ölçüldü. MDTA tedavisini takiben, her bir denein abdomeni üzerindeki üç bitiik cilt bölgesine (10 cm2) püskürtülen 1 mg estradiol, cilt tahriine neden olmad. Kan estradiol konsantrasyonlar dört kadnda ölçülmütür (yalar 54 ile 63 arasnda, vücut arl 67 ile 93 kg arasndadr). Ortalama kan estradiol konsantrasyonu, 9 günlük çalma süresi boyunca 53 pg / mL idi ve bu, 13 pg / mL referans deerinden önemli ölçüde daha yüksekti. (p <0,001). Bu test, etilheksil dimetil PABA içeren MDTA’nn estradiolün transdermal datmn arttrdn dorulad. Etanol içinde 14C etiketli etilheksil dimetil PABA, dört erkek ve dii denein her birinin ön kollarnn 100 cm2’sine uyguland. Ön kollar daha sonra etanol tamamen buharlatktan sonra 24 saat boyunca gazl bezle kapatld. 0, 2, 4, 8, 24 ve 72 saat sonra kan topland ve 24 saat idrar topland. Kan örneklerinde radyoaktivite bulunmazken, erkek ve dii deneklerin idrar örneklerinde srasyla% 2,45 ve% 1,18 radyoaktivite (ortalama% toplam radyoaktivite) bulundu. Uygulama yerinde cildin ykanmasndan sonra geri kazanlan ortalama radyoaktivite% 95,7 idi. 0.5 mg / cm2’nin% 8 ila 1.8 m2’lik bir konsantrasyonda uyguland varsayldnda, emilen toplam miktar 13 mg veya 0.2 mg / kg idi. Bir in vitro perkütan penetrasyon testi için suda ya emülsiyon losyonu kullanld ve membranlar olarak kobay ve insan derisi kullanld. HEPES tamponlu Hank’in gentamisin sülfat ve sr serum albümini içeren dengeli tuz çözeltisi, alc bölmede sulu çözelti olarak kullanld. Etilheksil dimetil PABA’nn toplam absorpsiyon oran, alc odaya aktarld ve deri,% 12.7 ± 2.5 idi. Etilheksil dimetil PABA metabolizmasnn deerlendirilmesi de bu teste dahil edildi. Kobay derisi, etilheksil dimetil PABA’nn yaklak% 13-35’ini hidrolize ederken esteraz aktivitesi yoluyla sulu çözeltiye aktarlrken, insan cildi etilheksil dimetil PABA’nn% 37’sini hidrolize etti. nsanlarda cilt absorpsiyonu için risk deerlendirmesi için kullanlan deer, snrl cilt absorpsiyon verilerine göre% 2.45’tir.