Developmental toxicity of UV filters and environmental exposure: a review.
Several ultraviolet (UV) filters exhibit estrogenic, some also anti-androgenic activity. They are present in waste water treatment plants, surface waters and biosphere including human milk, suggesting potential exposure during development. Developmental toxicity was studied in rats for the UV filters 4-methylbenzylidene camphor (4-MBC, 0.7, 7, 24, 47 mg/kg/day) and 3-benzylidene camphor (3-BC, 0.07, 0.24, 0.7, 2.4, 7 mg/kg/day) administered in chow to the parent generation before mating, during pregnancy and lactation, and to the offspring until adulthood. Neonates exhibited enhanced prostate growth after 4-MBC and altered uterine gene expression after both chemicals. 4-MBC and 3-BC delayed male puberty and affected reproductive organ weights of adult offspring. Effects on the thyroid axis were also noted. Expression and oestrogen sensitivity of oestrogen-regulated genes and nuclear receptor coregulator levels were altered at mRNA and protein levels in adult uterus, prostate and brain regions involved in gonadal control and sexual behaviour. Female sexual behaviour was impaired by both filters; 3-benzylidene camphor caused irregular cycles. Classical endpoints exhibited lowest observed adverse effect levels (LOAELs) and no observed adverse effect levels (NOAELs) of 7/0.7 mg/kg for 4-MBC and 0.24/0.07 mg/kg for 3-BC. Molecular endpoints were affected by the lowest doses studied. Our data indicate that the potential risk posed by endocrine active UV filters warrants further investigations.
Schlumpf
Margret
M
GREEN Tox and Institute of Anatomy, University of Zurich, Zurich, Switzerland. margret.schlumpf@access.uzh.ch
Durrer
Stefan
S
Faass
Oliver
O
Ehnes
Colin
C
Fuetsch
Michaela
M
Gaille
Catherine
C
Henseler
Manuel
M
Hofkamp
Luke
L
Maerkel
Kirsten
K
Reolon
Sasha
S
Timms
Barry
B
Tresguerres
Jesus A F
JA
Lichtensteiger
Walter
W
D000818:Animals; D001593:Benzyl Compounds / Q000633:toxicity*; D002164:Camphor / Q000031:analogs & derivatives* / Q000633:toxicity; D004702:Endocrine Glands / Q000187:drug effects; D004781:Environmental Exposure; D004967:Estrogens / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019055:No-Observed-Adverse-Effect Level; D012726:Sexual Behavior, Animal; D013723:Teratogens / Q000633:toxicity*; D014466:Ultraviolet Rays
D001593:Benzyl Compounds; D004967:Estrogens; D013723:Teratogens; C511303:3-benzylidene camphor; D002164:Camphor; C038939:enzacamene