title: Individual and combined in vitro (anti)androgenic effects of certain food additives and cosmetic preservatives.
abstract: The individual and combined (binary mixtures) (anti)androgenic effect of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) was evaluated using the MDA-kb2 cell line. Exposing these cells to AR agonists results in the expression of the reporter gene (encoding for luciferase) and luminescence can be measured in order to monitor the activity of the reporter protein. In case of the evaluation of the anti-androgenic effect, the individual test compounds or binary mixtures were tested in the presence of a fixed concentration of a strong AR agonist (1000 pM 5-alpha-dihydrotestosterone; DHT). Cell viability was assessed using a resazurin based assay. For PG, this is the first report in the literature concerning its (anti)androgenic activity. In case of both individual and mixture testing none of the compounds or binary combinations showed androgenic activity. When tested in the presence of DHT, BuPB, BHA and BHT proved to be weak anti-androgens and this was confirmed during the evaluation of binary mixtures (BuPB+BHA, BuPB+BHT and BHA+BHT). Besides performing the in vitro testing of the binary combinations, two mathematical models (dose addition and response addition) were evaluated in terms of accuracy of prediction of the anti-androgenic effect of the selected binary mixtures. The dose addition model guaranteed a good correlation between the experimental and predicted data. However, no estimation was possible in case of mixtures containing PG, due to the lack of effect of the compound in case of the individual testing.
authors.affiliation: Toxicology Department, Iuliu Hatieganu University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania. Electronic address: anca.pop@umfcluj.ro.
authors.forename: Anca
authors.initials: A
authors.lastname: Pop
authors.affiliation: Medical Informatics and Biostatistics Department, Iuliu Hatieganu University of Medicine and Pharmacy, Faculty of Medicine, Cluj-Napoca, Romania. Electronic address: tdrugan@umfcluj.ro.
authors.forename: Tudor
authors.initials: T
authors.lastname: Drugan
authors.affiliation: Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), Esch-sur-Alzette, Luxembourg. Electronic address: arno.gutleb@list.lu.
authors.forename: Arno C
authors.initials: AC
authors.lastname: Gutleb
authors.affiliation: Toxicology Department, Iuliu Hatieganu University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania. Electronic address: lupu.diana@umfcluj.ro.
authors.forename: Diana
authors.initials: D
authors.lastname: Lupu
authors.affiliation: Toxicology Department, Iuliu Hatieganu University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania. Electronic address: cherfanjul@gmail.com.
authors.forename: Julien
authors.initials: J
authors.lastname: Cherfan
authors.affiliation: Toxicology Department, Iuliu Hatieganu University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania. Electronic address: floghin@umfcluj.ro.
authors.forename: Felicia
authors.initials: F
authors.lastname: Loghin
authors.affiliation: Toxicology Department, Iuliu Hatieganu University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania. Electronic address: kbela@umfcluj.ro.
authors.forename: Béla
authors.initials: B
authors.lastname: Kiss
mesh_terms: D000726:Androgen Antagonists / Q000633:toxicity*; D000728:Androgens / Q000494:pharmacology; D000975:Antioxidants / Q000633:toxicity; D002083:Butylated Hydroxyanisole / Q000633:toxicity; D002084:Butylated Hydroxytoluene / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003358:Cosmetics; D013196:Dihydrotestosterone / Q000494:pharmacology; D052244:Endocrine Disruptors / Q000633:toxicity*; D005503:Food Additives / Q000633:toxicity*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010226:Parabens / Q000633:toxicity; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D011435:Propyl Gallate / Q000633:toxicity; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D000975:Antioxidants; D003358:Cosmetics; D052244:Endocrine Disruptors; D005503:Food Additives; D010226:Parabens; D011310:Preservatives, Pharmaceutical; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; C038091:butylparaben; D011435:Propyl Gallate; D008156:Luciferases
keywords: Anti-androgen; Endocrine disruptor; In vitro; Luciferase; Mixture