Endocrine-Mediated Effects of a Benzophenone Related Chemical, 2,3,4,4'-Tetrahydroxybenzophenone, Based on Uterotrophic Assay, Hershberger Assay, and Subacute Oral Toxicity Study

Kanji Yamasaki

doi:10.4172/2161-0495.1000129

Abstract

The purpose of this study was to investigate the endocrine-mediated effects of a benzophenone-relative compound, 2,3,4,4’-tetrahydroxybenzophenone, based on the OECD protocols. In the uterotrophic assay, female SD rats were subcutaneously injected with the chemical at doses of 0, 100, 300, and 1,000 mg/kg on each of 3 days from postnatal day 20 to day 22, and the uterine weight of rats given the 300 and 1,000 mg/kg doses of the test chemical increased. In the Hershberger assay, the test chemical was orally administered at doses of 0, 60, 200, and 600 mg/kg/day to castrated male SD rats for 10 consecutive days beginning on postnatal day 56, and no changes were observed. On the other hand, when the test chemical was orally administered at doses 0, 60, 200, and 600 mg/kg/day for at least 28 days, serum T4 values decreased in male rats in the 600 mg/kg group. This suggests a mechanism of action related to the inhibition of thyroid peroxidase. The uterotrophic assay used in this study showed that the chemical has estrogen-agonist properties, however, estrogenic effects were not observed in a 28-day repeated-dose toxicity study. On the other hand, endocrine-mediated effects such as thyroid hormone dysfunction were detected in growing rats based on the results of the OECD test guideline No. 407.

Highlights

Since it was reported that a considerable number of chemicals may have endocrine-disrupting activity in humans and animals, the Organization for Economic Co-operation and Development (OECD) reviewed the original OECD Test Guideline No 407 and introduced in vivo screening tests in 2008 to detect endocrine-mediated effects
We did not examine the following organs listed in the current OECD Test Guideline 407 because we focused on the changes in endocrine-related organs: stomach, intestine, urinary bladder, eye ball, Harderian gland, sciatic nerve and spinal cord
The wet, blotted, and relative weights of the uteri of rats given EE increased compared to the rats given vehicle alone, and the uterine weights of rats given tamoxifen plus EE decreased compared to the rats given EE alone

Summary

Introduction

Since it was reported that a considerable number of chemicals may have endocrine-disrupting activity in humans and animals, the Organization for Economic Co-operation and Development (OECD) reviewed the original OECD Test Guideline No 407 and introduced in vivo screening tests in 2008 to detect endocrine-mediated effects. 2,3’,4,4’-tetrahydroxybenzophenone has been reported to have potent estrogenic activity in human breast cancer cell line MCF7 and androgenic activity in rat fibroblast cell line NIH3T3, a structurally related 2,3,4,4’-tetrahydroxybenzophenone has no estrogenic and androgenic properties [5]. These facts demonstrated that the endocrine-mediated activity differs among hydrated benzophenones. We subjected 2,3,4,4’-tetrahydroxybenzophenone to an uterotrophic assay, the Hershberger assay and TG 407 assay according to the OECD protocols to investigate whether it has endocrinemediated effects

Objectives

Methods

Results

Conclusion