A One-Generation Reproductive Toxicity Study of 3,4-Methylenedioxy-N-Methamphetamine (MDMA, Ecstasy), an Amphetamine Derivative, in C57BL/6 Mice

作者:Kwack Seung Jun; Yoon Kyung Sil; Lim Seong Kwang; Gwak Hyo min; Kim Ji Yun; Um Yoon Mi; Lee Jung Dae; Hyeon Ji Hyeon; Kim Yeon Joo; Kim Hyung Sik; Lee Byung Mu*
来源:Journal of Toxicology and Environmental Health Part A: Current Issues , 2014, 77(22-24): 1431-1442.
DOI:10.1080/15287394.2014.951759

摘要

3,4-Methylenedioxy-N-methamphetamine (MDMA, ecstasy) is an amphetamine derivative and is a popular type of drug that is abused due to its effects on the central nervous system (CNS), including alertness and euphoria. However, life-threatening (brain edema, heart failure, and coma) and fatal hyperthermia sometimes occur in some individuals taking MDMA. In a one-generation reproductive toxicity study, the potential toxicity of chronic exposure of MDMA was investigated on the reproductive capabilities of parental mice (F0), as well as the survival/development of their subsequent offspring (F1). Male and female C57BL/6 mice were administered orally MDMA at 0, 1.25, 5 or 20 mg/kg body weight (b.w.) throughout the study, beginning at the premating period, through mating, gestation, and lactation periods. MDMA did not produce any apparent clinical signs in F0 or F1 mice, and produced no significant changes in body weight, feed/water intake, or organ weights. In contrast, administration of MDMA produced external abnormalities in fetuses, stillbirth and labored delivery, and diminished viability and weaning indices in offspring, but these data were not significant. In addition, physical development of F1 mice was not markedly influenced by MDMA treatment. Nonetheless, serum biochemistry markers showed that levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) were markedly elevated in a dose-dependent manner from 5 mg and higher MDMA/kg b.w., whereas levels of triglycerides (TG), potassium (K), and uric acid (UA) were reduced. Data suggest that MDMA may exert a weak reproductive and developmental toxicity, and the no-observed-adverse-effect level (NOAEL) of MDMA is estimated to be 1.25 mg/kg b.w./d.

  • 出版日期2014-12-17