Endocrine adverse effects of mono(2-ethylhexyl) phthalate and monobutyl phthalate in male pubertal rats

Considering that research of adverse effects of mono(2-ethylhexyl) phthalate (MEHP) and monobutyl phthalate (MBP), two key metabolites of the most common phthalates used as plasticisers in various daily-life products, has been scattered and limited, the aim of our study was to provide a more comprehensive analysis by focusing on major organ systems, including blood, liver, kidney, and pancreas in 66 male pubertal rats randomised into eleven groups of six. The animals were receiving either metabolite at doses of 25, 50, 100, 200, or 400 mg/kg bw a day by gavage for 28 days. The control group was receiving corn oil. At the end of the experiment, blood samples were collected for biochemical, haematological, and immunological analyses. Samples of kidney, liver, and pancreas were dissected for histopathological analyses. Exposure to either compound resulted in increased liver and decreased pancreas weight, especially at the highest doses. Exposed rats had increased ALT, AST, glucose, and triglyceride levels and decreased total protein and albumin levels. Both compounds increased MCV and decreased haemoglobin levels compared to control. Although they also lowered the insulin level, exposed rats had negative islet cell and insulin antibodies, same as control. Treatment-related histopathological changes included sinusoidal degeneration in the liver, glomerular degeneration in the kidney, and degeneration of pancreatic islets. Our findings document toxic outcomes of MEHP and MBP on endocrine organs in male pubertal rats but also suggest the need for additional studies to better understand the mechanisms behind adverse effects in chronic exposure.