Endocrine activity and developmental toxicity of cosmetic UV filters - an update

被引:319
作者
Schlumpf, M
Schmid, P
Durrer, S
Conscience, M
Maerkel, K
Henseler, M
Gruetter, M
Herzog, I
Reolon, S
Ceccatelli, R
Faass, O
Stutz, E
Jarry, H
Wuttke, W
Lichtensteiger, W
机构
[1] Univ Zurich, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland
[2] EMPA, Dubendorf, Switzerland
[3] Univ Gottingen, Dept Clin & Expt Endocrinol, D-3400 Gottingen, Germany
关键词
UV filters; 4-methylbenzylidene camphor (4-MBC); 3-benzylidene camphor (3-BC); estrogenic; development; toxicity; gene expression;
D O I
10.1016/j.tox.2004.06.043
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
UV filters represent a new class of endocrine active chemicals. In vitro, 8/9 chemicals showed estrogenic (MCF-7 cells), and 2/9 antiandrogenic activity (MDA-kb2 cells). Six/nine filters (benzophenone (Bp)-1, Bp-2, Bp-3, 3-benzylidene camphor (3-BC), 4-methylbenzylidene camphor (4-MBC), octyl-niethoxycinnamate (OMC)) increased uterine weight in immature rats. 3-Benzylidene camphor and 4-MBC displaced 16alpha I-125-estradiol from human estrogen receptor (ER)P, not ERalpha. Developmental toxicity of 4-MBC (0.7-47 mg/kg body weight/day) and 3-BC (0.24-7 mg/kg), administered in chow was investigated in Long Evans (LE) rats. Weight gain of pregnant rats was reduced only by 3-BC, early postnatal survival rate and thymus weight by both compounds at higher doses. 4-Methylbenzylidene camphor and 3-BC delayed male puberty, and dose-dependently affected reproductive organ weights of adult male and female F1 offspring, with partly different effect patterns. Thyroid weight was increased by higher 4-MBC doses. Tissue-specific changes in mRNA levels of estrogen-regulated genes in prostate, uterus and brain regions, determined by real-time PCR, and in their response to acute estradiol challenge in adult gonadectomized offspring were observed. Lowest effective doses were 0.24 mg/kg/day for 3-BC and 7 rng/kg/day for 4-MBC. Fat tissue levels at 7 mg/kg 4-MBC (GC-MS) approached the range of UV filters in fish (Nagtegaal et al., 1997; Balmer et al., 2004). (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:113 / 122
页数:10
相关论文
共 27 条
[11]   UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay [J].
Ma, RS ;
Cotton, B ;
Lichtensteiger, W ;
Schlumpf, M .
TOXICOLOGICAL SCIENCES, 2003, 74 (01) :43-50
[12]  
MAERKEL K, IN PRESS ENV TOXICOL
[13]   Activation of estrogen receptor α and ERβ by 4-methylbenzylidene-camphor in human and rat cells:: comparison with phyto- and xenoestrogens [J].
Mueller, SO ;
Kling, M ;
Firzani, PA ;
Mecky, A ;
Duranti, E ;
Shields-Botella, J ;
Delansorne, R ;
Broschard, T ;
Kramer, PJ .
TOXICOLOGY LETTERS, 2003, 142 (1-2) :89-101
[14]   Reproductive effects in male and female rats of neonatal exposure to genistein [J].
Nagao, T ;
Yoshimura, S ;
Saito, Y ;
Nakagomi, M ;
Usumi, K ;
Ono, H .
REPRODUCTIVE TOXICOLOGY, 2001, 15 (04) :399-411
[15]  
Nagtegaal M., 1997, UWSF-Z fur Umweltchem Okotox, V9, P79, DOI DOI 10.1007/BF02937843
[16]   Effects of an intrahypothalamic injection of antisense oligonucleotides for preproenkephalin mRNA in female rats: evidence for opioid involvement in lordosis reflex [J].
Nicot, A ;
Ogawa, S ;
Berman, Y ;
Carr, KD ;
Pfaff, DW .
BRAIN RESEARCH, 1997, 777 (1-2) :60-68
[17]   EFFECTS OF INTRAHYPOTHALAMIC ADMINISTRATION OF ANTISENSE DNA FOR PROGESTERONE-RECEPTOR MESSENGER-RNA ON REPRODUCTIVE-BEHAVIOR AND PROGESTERONE-RECEPTOR IMMUNOREACTIVITY IN FEMALE RAT [J].
OGAWA, S ;
OLAZABAL, UE ;
PARHAR, IS ;
PFAFF, DW .
JOURNAL OF NEUROSCIENCE, 1994, 14 (03) :1766-1774
[18]  
*SCCNFP, OP SCI COMM COSM PRO
[19]   In vitro and in vivo estrogenicity of UV screens [J].
Schlumpf, M ;
Cotton, B ;
Conscience, M ;
Haller, V ;
Steinmann, B ;
Lichtensteiger, W .
ENVIRONMENTAL HEALTH PERSPECTIVES, 2001, 109 (03) :239-244
[20]   Estrogenic activity and estrogen receptor β binding of the UV filter 3-benzylidene camphor comparison with 4-methylbenzylidene camphor [J].
Schlumpf, M ;
Jarry, H ;
Wuttke, W ;
Ma, R .
TOXICOLOGY, 2004, 199 (2-3) :109-120