The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP in March 2009 (see http://ntp.niehs.nih.gov/ntp/Test_info/NTP_DevTox20090405.pdf). The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.
Final Study Report
Developmental Toxicity Evaluation for Alpha-Solanine (CAS No. 20562-02-1) Administered by Gavage to Swiss (CD-1®) Mice on Gestational Days 6-16
NTP Study: TER20002
Alpha-solanine is a naturally occurring glycoal-kaloid found in some common varieties of plants, particularly in the Solanum spp (Night-shades) genus. The potential developmental toxicity of alpha-solanine had previously been investigated, but fetal morphology had not been evaluated in rodents exposed orally throughout embryo/fetal development except in a previ-ously conducted screening study (NTP, 2001). In the present study, timed-mated CD-1® mice were exposed by gavage to 0, 50, 100, or 200 mg/kg/day alpha-solanine in corn oil on gestational days (gd) 6 through 16. There were no maternal deaths in this study. At termination (gd 17), 23-25 pregnancies/group were confirmed. Clinical signs were mild, observed primarily in the high dose group (1-4 animals/day), and consisted of weight loss, efflux of dosing solution, vaginal bleeding, or rough coat.
Maternal body weight was decreased at the high dose on gd 16 and 17 (greater than or equal to 90% of the control values). Maternal weight gain was reduced at the high dose for gd 15 to 16 and gd 16 to 17 (greater than or equal to 59% of the control values), during treatment (85% of the control) and during gestation (81% of the control. In addition, maternal gestational body weight corrected for gravid uterine weight was 71% of the control value at the high dose. Gravid uterine weight (85% of the control value) was also significantly decreased at the high dose. Maternal liver weights were reduced at the mid dose (absolute) and at the high dose (absolute and relative), further suggesting primary maternal toxicity at the high dose.
Maternal absolute feed consumption exhibited a decreasing trend for all intervals after initiation of dosing on gd 6, and was significantly decreased at the high dose on gd 6 to 9, 9 to 12, 15 to 16, 16 to 17, 6 to 16 (treatment) and 0 to 17 (gestation). Maternal relative feed consumption, however, exhibited a decreasing trend on gd 6 to 9 and 9 to 12, but was not significantly decreased at any treatment level compared to the control group. Maternal absolute water consumption was equivalent across treatment groups prior to gd 12. However, a decreasing trend was observed for maternal absolute water consumption on gd 12 to 15, 15 to 16, 16 to 17, 6 to 16 (treatment) and 0 to 17 (gestation). These decreases were significant at the high dose on gd 12 to 15, 15 to 16, 16 to 17, and 0 to 17. Maternal relative water intake exhibited a decreasing trend on gd 15 to 16 and 16 to 17. Maternal relative water consumption was significantly decreased at the high dose of alpha-solanine on gd 15 to 16, but not at any other time during gestation.
There were no differences among groups for the number of corpora lutea/dam, number of implantation sites/litter, or percent preimplantation loss/litter. Postimplantation loss (resorptions or late fetal deaths), live litter size, and the percent male fetuses/litter were all unaffected by treatment. Alpha-solanine at 200 mg/kg/day did cause a significant decreasing trend for fetal body weight (male, female, and the sexes combined). This decrease was significant for males and for the sexes combined (91 and 92% of the control values, respectively), but not females. Alpha-solanine did not affect the incidence of fetal malformations or variations.
In summary, the LOAEL for maternal toxicity for alpha-solanine under the conditions of this study was considered to be 200 mg/kg/day, based on measures of maternal body weight, weight gain, relative liver weight, and feed consumption. The NOAEL for maternal toxicity was 100 mg/kg/day. The LOAEL for developmental toxicity under the conditions of this study was considered to be 200 mg alpha-solanine/kg/day, based on fetal body weight. The NOAEL for developmental toxicity was 100 mg/kg/day. No evidence of teratogenic potential was observed for alpha-solanine at doses up to 200 mg/kg/day, administered on gd 6 through 16. Thus, it appears that the fetal mouse is not uniquely sensitive, relative to the maternal animal, to the toxic properties of alpha-solanine under the specified experimental conditions.
Report Date: July 30, 2002