A one-generation reproductive toxicity study of 3,4-methylenedioxy-n-methamphetamine (MDMA, Ecstasy), an amphetamine derivative, in C57BL/6 mice.

Abstract

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.

• Authors: Seung Jun Kwack, Kyung Sik Yoon, Seong Kwang Lim, Hyo-Min Gwak, Ji Yun Kim, Yoon Mi Um, Jung Dae Lee, Ji Hyeon Hyeon, Yeon Joo Kim, Hyung Sik Kim, Byung-Mu Lee
• Journal: Journal of toxicology and environmental health. Part A (J Toxicol Environ Health A) Vol. 77 Issue 22-24 Pg. 1431-42 ( 2014) ISSN: 1528-7394 [Print] England
• PMID: 25343292 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• N-Methyl-3,4-methylenedioxyamphetamine

Topics

• Animals
• Body Weight (drug effects)
• Brain (drug effects, pathology)
• Dose-Response Relationship, Drug
• Female
• Kidney (drug effects, pathology)
• Lactation (drug effects)
• Liver (drug effects, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• N-Methyl-3,4-methylenedioxyamphetamine (toxicity)
• No-Observed-Adverse-Effect Level
• Organ Size
• Reproduction (drug effects)
• Spleen (drug effects, pathology)
• Testis (drug effects, pathology)