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Archives of Toxicology

, Volume 80, Issue 10, pp 656–661 | Cite as

A dose-response study on the estrogenic activity of benzophenone-2 on various endpoints in the serum, pituitary and uterus of female rats

  • Christiane Schlecht
  • Holger Klammer
  • Wolfgang Wuttke
  • Hubertus JarryEmail author
Organ Toxicity and Mechanisms

Abstract

The tetrahydroxylated biphenyl-ketone 2,2′,4,4′-tetrahydroxybenzophenone (BP2), one of twelve benzophenone-derived UV-filters, is used in cosmetic products and in packaging materials to protect these products from light induced damage. Recently published studies showed that BP2 exerts estrogenic activity; thus, it is an endocrine active chemical. We present data from a pharmacodynamic dose-response experiment with five dosages of BP2 applied per gavage to adult ovariectomized (ovx) rats for 5 days. Estradiol-valerate (E2) served as a control compound. The uterotrophic assay, proposed by the OECD, was modified to have a broader view on endocrine activity outside the urogenital tract to prevent that undesirable actions in other organs regulated by estrogens are missed. The gene expression levels of marker genes of estrogenic action were measured by semi-quantitative RT-PCR. Metabolic parameters were assessed by determination of the serum concentrations of leptin, cholesterol, high- and low-density lipoproteins, and triglycerides in the serum. Administration of BP2 at dosages of 10–1,000 mg/kg bodyweight led to changes of these parameters comparable to the changes in the E2 group with 0.6 mg/kg bodyweight. For the observed estrogenic activities of BP2, the “no observed adverse effect levels” were determined. Additionally, the data were further analyzed using the benchmark approach. If BP2 is transcutaneously absorbed in the human, the obtained threshold values would suggest refraining from the further use of BP2 as UV-filter in cosmetic products although additional toxicological studies should be conducted to clarify possible adverse effects.

Keywords

2,2′,4,4′-tetrahydroxybenzophenone BP2 Multi-organic risk assessment Estradiol Estrogen receptor Benchmark approach Rat 

Abbreviations

BP2

Benzophenone-2

E2

Estradiol-valerate

C3

Complement protein 3

TERP1

Truncated estrogen receptor protein 1

ER

Estrogen receptor

IGF1

Insulin-like growth factor 1

H/LDL

High/low density lipoprotein

LH

Luteinizing hormone

EAC

Endocrine active chemical

N/LOAEL

No/lowest observed adverse effect level

CED

Critical effect dose

CES

Critical effect size

CL

Confidence limit

α-subunit

Subunit of the hormones FSH, TSH and LH

Notes

Acknowledgement

This work was in part supported by the European Commission (EURISKED contract no. EVK1-CT2002-00128). The authors wish to thank Bas Bokkers from the IRAS (The Netherlands) for the help on the modeling process with the PROAST 02.R software. All experiments were performed according to the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes (ETS 123) and GLP guidelines published by the OECD.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Christiane Schlecht
    • 1
  • Holger Klammer
    • 1
  • Wolfgang Wuttke
    • 1
  • Hubertus Jarry
    • 1
    Email author
  1. 1.Department of Clinical and Experimental EndocrinologyUniversity of GoettingenGoettingenGermany

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