Effects of pre- and postnatal exposure to the UV-filter octyl methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring.
Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T(4)), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. On postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T(4)) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T(4) deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the reproductive and neurological development of rat offspring, which may be a cause of concern, as humans are systematically exposed to the compound through usage of sunscreens and other cosmetics.
Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark. maap@food.dtu.dk
Marta
M
Axelstad
Julie
J
Boberg
Karin Sørig
KS
Hougaard
Sofie
S
Christiansen
Pernille Rosenskjold
PR
Jacobsen
Karen Riiber
KR
Mandrup
Christine
C
Nellemann
Søren Peter
SP
Lund
Ulla
U
Hass
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002934:Cinnamates / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004958:Estradiol / Q000097:blood; D005260:Female; D006128:Growth / Q000187:drug effects; D006309:Hearing / Q000187:drug effects*; D007774:Lactation / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D018782:Maze Learning / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects; D012661:Semen / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects; D013473:Sunscreening Agents / Q000008:administration & dosage / Q000633:toxicity*; D013739:Testosterone / Q000097:blood; D013974:Thyroxine / Q000097:blood
D002934:Cinnamates; D052244:Endocrine Disruptors; D013473:Sunscreening Agents; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; C118580:octylmethoxycinnamate; D013974:Thyroxine