Projects
12: UV filters: Mechanisms of developmental toxicity in mammalian brain and human exposure.
Endocrine disruptive effects in mammals by UV screens.
UV filters interfere with endocrine mechanisms. They can disturb developmental processes in mammals. Effects of endocrine disruptors on structure, functions, and gene expression patterns are visualized in the developing brain. Data of human milk samples will fill major gaps in human risk assessment.
Schlumpf Margret, GREEN Tox
e-mail: Margret.Schlumpf@access.unizh.ch
Background
UV filters have been identified in vitro and in vivo as a new group of endocrine disruptors. These are high production volume chemicals with an increasingly diverse spectrum of use as additives. They are released into the environment and are detectable in wastewater, rivers, lakes, in fish and in human milk.
Animals and humans may be exposed to these compounds via the food chain, and humans in particular may be affected transdermally when applying sunscreens and cosmetics. Two of the filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC), have been tested for developmental toxicity. In addition to changes in classical toxicological endpoints we also noted changes at the molecular level such as tissue-specific changes in mRNA levels of estrogen-regulated genes, both in peripheral organs and in the brain. The widespread use of UV filters and the evidence for their presence in the biosphere indicate a need for more extensive risk assessment.
Aim
In subproject A we will address the mechanistic background of developmental toxicity of 4-MBC and 3-BC administered at low doses, contributing to general knowledge of their interactions with the developing organism. The focus will be on the brain, which exhibits particular sensitivity. We will analyse effects of 4-MBC and 3-BC on growth factors and steroid receptor coregulators known to influence early brain development and sexual brain differentiation.
By means of subproject B we aim to fill a major gap in the assessment of the risk posed by environmental chemicals to humans. Human milk samples will be analysed for 6 different UV filters, as well as for parabens, chlorinated organic compounds, polybrominated diphenyl ethers and synthetic musks. Data on 4-MBC and 3-BC levels in human milk will then be compared with rat adipose tissue concentrations at the effect level.
Significance
Our investigations will increase knowledge about the molecular interactions of endocrine disruptors in the developing brain. This should strengthen the basis for interspecies extrapolation from rat to humans or from rat to wild life species. A risk assessment for internal exposure of humans and experimental animals to 4-MBC should be possible with the results from the human milk study. Our investigations will shed new light on the role of endocrine mechanisms in developmental processes and their disturbance by environmental chemicals. This work will contribute to creating a more solid basis for risk assessment.