Toxicology Letters 99 (1998) 71 – 77 Dominant lethal study of  -asarone in male mice Germa ´n Chamorro a, *, Leticia Gardun ˜o a , Elizdath Martı ´nez a , Eduardo Madrigal b , Joaquı ´n Tamariz c , Marı ´a Salazar a a Departamento de Toxicologı ´a, Escuela Nacional de Ciencias Biolo ´gicas, Instituto Polite ´cnico Nacional, Apartado Postal 105 -314, C.P. 11591, Me ´xico D.F., Mexico b Departamento de Morfologı ´a, Escuela Nacional de Ciencias Biolo ´gicas, Instituto Polite ´cnico Nacional, Me ´xico D.F., Mexico c Departamento de Quı ´mica, Escuela Nacional de Ciencias Biolo ´gicas, Instituto Polite ´cnico Nacional, Me ´xico D.F., Mexico Received 4 December 1997; received in revised form 23 April 1998; accepted 23 April 1998 Abstract  -Asarone is a hypolipidaemic agent obtained from Guatteria gaumeri, a medical plant used in Mexico to treat hypercholesteraemia and cholelithiasis.  -Asarone has been shown to be hepatocarcinogenic and mutagenic in a human lymphocyte assay, a murine bone marrow cell assay and in an unscheduled DNA synthesis assay. In this study,  -asarone was tested for dominant lethal effects in male CF1 mice. The drug was given orally at doses of 0, 10 and 30 mg/kg per day for 5 days. Males were mated weekly with eight consecutive batches of naive, nulliparous female mice. Repeated matings revealed no perceptible effect of  -asarone on the incidence of pregnancy. Examina- tion of surgically exposed uteri and ovaries of pregnant females on day 13 – 15 of gestation revealed an increased incidence of post-implantation loss. Semen examination of a separate group of mice showed a decreased concentra- tion and motility of spermatozoa. These results suggest a dominant lethal mutation as well as direct  -asarone toxicity to spermatozoa by in treated mice. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords:  -Asarone; Genotoxicity; Hypocholesteraemia; Hypolipidaemia 1. Introduction Guatteria gaumeri (Annonaceae) is a medicinal plant traditionally used in Yucata ´n (Southeast of Mexico) to treat hypercholesteraemia and cholelithiasis, as described by previous studies in healthy and hypercholesteraemic volunteers (Martı ´nez, 1982; Sa ´nchez-Rese ´ndiz and Lerdo de Tejada 1982). It is commonly known as ‘yumel’ in the vernacular Mayan language (Dehaussy et al., 1983) and has been marketed in some coun- tries (Leclercq et al., 1985). The active pharmaco- logical agent of this plant is a trans isomer of * Corresponding author. E-mail: chamorro@bios.encb. ipn.mx 0378-4274/98/$ - see front matter © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0378-4274(98)00041-1