title: Toxicological evaluation of isopropylparaben and isobutylparaben mixture in Sprague-Dawley rats following 28 days of dermal exposure.
abstract: The alkyl esters of p-hydroxybenzoic acid (Parabens) have been of concern due to their probable endocrine disrupting property especially in baby consumer products. The safety of parabens for use as a preservative in cosmetics has come into controversy, and thus consumer demand for paraben-free products is ever increasing. Thus, more comprehensive studies are needed to conclusively determine the safety of the multiple prolonged exposure to parabens with cosmetic ingredients. This study was conducted to investigate the potential repeated 28 days dermal toxicity (50, 100, 300, or 600 mg/kg bw/day) of isopropylparaben (IPP), isobutylparaben (IBP), or the mixture of IPP and IBP in rats. There were no significant changes in body and organ weights in any group. However, histopathological examinations showed that weak or moderate skin damages were observed in female rats by macroscopic and microscopic evaluations. In female rats, no observed adverse effect levels (NOAELs) of IPP with no skin lesion and IBP for skin hyperkeratosis, were estimated to be 600 mg/kg bw/day, and 50 mg/kg bw/day, respectively. With regard skin hyperkeratosis, the lowest observed adverse effect level (LOAEL) of the mixture of IPP and IBP was estimated to be 50 mg/kg bw/day. Analysis of six serum hormones (estrogen, testosterone, insulin, T3, TSH, or FSH) in animals showed that only FSH was dose-dependently decreased in the mixture groups of 100 mg/kg bw/day or higher. These data suggest that the mixture of IPP and IBP showed a synergistic dermal toxicity in rats and should be considered for future use in consumer products.
authors.affiliation: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Health Science, College of Natural Sciences, Changwon National University, 92 Toechonro, Uichang-gu, Changwon, Gyeongnam 641-773, South Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kwack
authors.affiliation: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea.
authors.forename: Seong Kwang
authors.initials: SK
authors.lastname: Lim
authors.affiliation: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea.
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Roh
authors.affiliation: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea.
authors.forename: Seul Min
authors.initials: SM
authors.lastname: Choi
authors.affiliation: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea. Electronic address: hkims@skku.edu.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea. Electronic address: bmlee@skku.ac.kr.
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D010226:Parabens / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D063465:Skin Cream / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
chemical_list: D010226:Parabens; D019999:Pharmaceutical Solutions; D011310:Preservatives, Pharmaceutical; C471067:isobutylparaben
keywords: Cosmetics; Isobutylparaben; Isopropylparaben; Mixture toxicity; NOAEL