4-Hidroksibenzoik asit

Acute Dose Toxicity No new published acute toxicity studies were discovered and no unpublished data were submitted. 1984 Acute toxicity studies in animals indicate that parabens are practically nontoxic by various routes of administration.3 1986 Benzylparaben was not considered an acute toxic agent to mice or rats… Intravenous injections of Benzylparaben to dogs and cats caused no variation in blood sugar, circulation, and respiration.4 1995 Isobutylparaben had a subcutaneous LD50 of 2,600 mg/kg in mice.5 Short-Term Toxicity Studies 1995 No significant histological changes were observed in mice dosed with 0.6% Isobutylparaben in the feed for 6 weeks. Mice dosed with 1.25% had atrophy of the spleen, thymus, and lymph nodes as well as multifocal degeneration and necrosis of the hepatic parenchyma. Mice dosed with 5% and 10% Isobutylparaben died within the first 2 weeks of the study.5 Dermal Short-term dermal toxicity studies are presented in Table 11. There were no significant changes in body and organ weights in any group when rats were dermally exposed to up to 600 mg/kg bw/day Isopropylparaben or Isobutylparaben for 28 days.55 Macroscopic and microscopic examinations revealed mild-to-moderate skin damage in female rats. No-observed-adverse-effect-levels (NOAEL) for Isobutylparaben and Isopropylparaben were 600 mg/kg bw/day, and 50 mg/kg bw/day, respectively. Oral Short-term oral toxicity studies are presented in Table 11. At 100 and 300 mg/kg bw/day Propylparaben administered orally, rats exhibited statistically-significant increases in relative liver weights, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities, serum urea concentrations, lipid peroxidation and nitric oxide (NO) generation, … [kırpıldı — bölüm toplam 14030 karakter]

Definition and Structure Isobutylparaben (CAS No. 4247-02-3) and Isopropylparaben (CAS No. 4191- 73-5) are esters of p-hydroxybenzoate that conform to the following formulas (Nikitakis et al., 1991): 0 CH3 0 CH3 II I II I HO-o-C-O-CH2 -CH-CH3 HO-o-C-O-CH-CH3 lsobutylparaben Isopropylparaben Other names for Isobutylparaben are benzoic acid, 4-hydroxy-, 2-methylpropyl ester; 4-hydroxybenzoic acid, 2-methylpropyl ester; isobutyl p-hydroxybenzoate; isobutyl parahydroxybenzoate. Other names for Isopropylparaben are benzoic acid, 4-hydroxy-, 1-methylethyl ester; 4-hydroxybenzoic acid, 1-methylethyl es- ter; 1-methylethyl-4-hydroxybenzoate (Nikitakis et al., 1991). Chemical and Physical Properties Isobutylparaben has a molecular weight of 194.25. Isopropylparaben has a mo- lecular weight of 180.22 (Registry of Toxic Effects of Chemical Substances, 1993). Analytic Methods Detection of Isopropylparaben and Isobutylparaben can be made by high- performance liquid chromatography (Kitada et al., 1980; Terada and Sakabe, 1985; Shiroma and Oshiro, 1986; Maeda et al., 1987). JAm Col/ Toxicol, Vol. 14, No. 5, 1995  Distributed for comment only -- do not cite or quote 366 COSMETIC INGREDIENT REVIEW USE Cosmetic Isobutylparaben and Isopropylparaben are used in cosmetic formulations as preservatives (Nikitakis, 1988). The product formulation data submitted to the Food and Drug Administration (FDA) in 1993 reported that Isobutylparaben was … [kırpıldı — bölüm toplam 20117 karakter]

Dermal Penetration 2008 Parabens in cosmetic formulations applied to skin penetrate the stratum corneum in inverse relation to the ester chain length.6 Carboxylesterases present in keratinocytes hydrolyze parabens in the skin. The extent of the breakdown to PHBA is different between rodent and human skin. In vitro studies also indicate a difference in the extent of hydrolysis to PHBA, depending on whether viable whole skin or dermatomed human skin is used, with the former having a larger extent of hydrolysis. Chemicals that disrupt the stratum corneum may increase the skin penetration of Methylparaben and possibly Ethylparaben, but do not affect the penetration of parabens with longer ester chains. In Vitro In vitro dermal penetration studies are presented in Table 9. In Franz-type diffusion cells, 2.3%-3.3% of the applied concentration (0.1%) of Methylparaben penetrated porcine skin (fresh or after stored frozen) in 4 h.37 In 24 h, 2.0%- 5.8% and 2.9%-7.6% penetrated previously frozen intact and tape- stripped skin, respectively. In full-thickness porcine skin stored frozen, permeability coefficients ranged from 31.3 ± 1.6 to 214.8 ± 40 cm/h x 10-4, decreasing (Methylparaben>Ethylparaben>Propylparaben>Butylparaben) with increasing lipophilicity.38 Increasing the ethanol concentration or the exposure duration increased the retention of the parabens in the dermis, compared to the epidermis. Binary combinations of the parabens reduced their permeation rates, which was attributed by the authors to high retention in the epidermis and dermis. Penetration of parabens in 3 commercial facial cream through rabbit ear skin ranged from 20%-60%, after 8 h in Franz-type diffusion cells, increasing (Propylparaben < Ethylparaben < Methylparaben) with increasing water solubility of the paraben, regardless of the formulation tested.39 … [kırpıldı — bölüm toplam 13575 karakter]

Adverse Event Reports 1984 Industry complaint experience data showed low to moderate numbers of safety-related complaints with the incidence depending on the product.3  Distributed for comment only -- do not cite or quote EPIDEMIOLOGICAL STUDIES Primary Studies PROSPECTIVE STUDIES Prospective epidemiological studies are summarized in Table 14. Preterm birth (PTB) was associated with umbilical cord blood concentrations of Butylparaben (OR=60.77; CI=2.60- 1419.93) and Benzylparaben (OR=0.03, CI=0.01-0.44).88 Linear regression analysis indicated an association between maternal urinary concentrations and decreased gestational age and body length in newborns. No statistically-significant associations were observed between Methylparaben or Ethylparaben concentrations and the outcomes evaluated. In another prospective study, in vitro fertilization outcomes were not associated with urinary Methylparaben, Propylparaben, or Butylparaben concentrations of women undergoing treatments for infertility.89 No statistically-significant associations were found between prenatal or postnatal growth of male newborns and maternal urinary paraben concentrations of Methylparaben, Ethylparaben, Propylparaben, or Butylparaben.90 RETROSPECTIVE STUDIES Retrospective epidemiological studies are summarized in Table 14. The incidence of cryptorchidism and/or hypospadias, combined, was associated with placental concentrations of Methylparaben ≥1.96 ng/g (OR=3.18; CI=0.88-11.48) and Propylparaben concentrations ≥1.16 ng/g (OR=4.72; CI=1.08- 20.65).91 Linear regression analyses indicated an association between urinary Ethylparaben concentrations in 3-year old children and their body weights and heights.92 The latter parameter was also associated with calculated estimates of … [kırpıldı — bölüm toplam 36048 karakter]

No new published animal or human irritation and sensitization studies were discovered and no unpublished data were submitted. 1984 Methylparaben (100% and 10%), Propylparaben (10%), and Ethylparaben (100% and 10%) were, at most, mildly irritating when applied to rabbit skin.3 Parabens are practically nonirritating and in the [human] population with normal skin… Skin irritation and sensitization tests on product formulations containing from 0.1 to 0.8 percent of one or two of the parabens showed no evidence of significant irritation or sensitization potential for these ingredients. Parabens are practically nonsensitizing in the [human] population with normal skin. Paraben sensitization has occurred, especially when paraben-containing medicaments have been applied to damaged or broken skin. Even when applied to patients with chronic dermatitis, parabens generally induce sensitization in less than 3 percent of such individuals. Of 27,230 patients with chronic skin problems, 2.2 percent were sensitized by preparations of parabens at concentrations of 1 to 30 percent. Many patients sensitized to paraben-containing medications can wear cosmetics containing these ingredients with no adverse effects. Skin sensitization tests on product formulations containing from 0.1 to 0.8 percent of one or two of the parabens showed no evidence of significant irritation or sensitization potential for these ingredients. Practically all animal sensitization tests indicate that the parabens are nonsensitizing. 1986 Benzylparaben …was neither an eye nor skin irritant when tested in rabbits.4 Sensitization to Benzylparaben has been observed in eczematous patients. A 3% mixture of Benzylparaben, Methylparaben, Ethylparaben, Propylparaben, and Butylparaben produced positive reactions ranging from 1 to 3.7%. The … [kırpıldı — bölüm toplam 6599 karakter]

Cited by 194. Methyl paraben (CAS No. 99-76-3) is a methyl ester of p-hydroxybenzoic acid. It is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics for over 50 years. Methyl paraben is readily and completely absorbed through the skin and from the gastrointestinal tract. It is hydrolyzed to p-hydroxybenzoic acid, conjugated, and the conjugates are rapidly excreted

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: equivalent or similar to OECD Guideline 406 (Skin Sensitisation), yıl: 1952. Sınır: bu bir derleme kayıttır; doz, tür ve maruziyet yolu birlikte değerlendirilmelidir.

EPA ToxValDB cilt/göz verisi — endpoint: Skin Sensitization, sınıflandırma: Category 6.5B (Category 1). Sınır: bu bir derleme kayıttır; doz, tür ve maruziyet yolu birlikte değerlendirilmelidir.

EPA ToxValDB cilt/göz verisi — endpoint: Skin Irritation, sınıflandırma: Category 6.3B (Category 3). Sınır: bu bir derleme kayıttır; doz, tür ve maruziyet yolu birlikte değerlendirilmelidir.

EPA ToxValDB cilt/göz verisi — endpoint: Eye Irritation, sınıflandırma: Category 6.4A (Category 2A). Sınır: bu bir derleme kayıttır; doz, tür ve maruziyet yolu birlikte değerlendirilmelidir.

EPA ToxValDB cilt/göz verisi — endpoint: Skin Sensitization, sınıflandırma: Classification not possible. Sınır: bu bir derleme kayıttır; doz, tür ve maruziyet yolu birlikte değerlendirilmelidir.

EPA ToxCast ER modeli: östrojen reseptörü aktivitesi BULUNMADI (AUC agonist=0.00684, antagonist=1.88E-07). 18 in vitro deneyde test edildi. Sınır: in vitro tarama modelidir, doz/maruziyet bağlamı içermez; kozmetikteki kullanım seviyesinde insanda etki gösterdiği anlamına GELMEZ.