The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
This study was conducted to assess the potential for orally administered glyoxal trimeric dihydrate to cause developmental toxicity. The most common human exposure to GLOX occurs as a result of ingestion of heated foods, in cigarette smoke, and in ozonated drinking water. The lack of pertinent developmental toxicity data in the published literature prompted this study. GLOX was administered by gavage in water to artificially inseminated New Zealand White rabbits on gestation days 6 through 19 at levels of O and 50 mg/kg/day. Only the 50 mg/kg/day dose level was used in an effort to ensure some maternal toxicity while avoiding the severe toxicity observed at higher doses (National Toxicology Program, unpublished results). If notable developmental effects had been observed at this maternally toxic dose, lower doses would have been tested. Animals were observed daily for clinical signs and weighed on the mornings of gd 0, 3, 6 through 19, 25, and 30. Food weights were recorded for the animals in each group on gd 0, 3, 6, 9, 12, 15, 18, 19, 22, 25, 28, and 30. All animals were killed on gd 30 and examined for maternal body and organ weights, implant status, fetal weight, sex, and morphological development.
There was no maternal mortality during the study and there was no treatment-related increase in the incidence of clinical signs. Maternal absolute and relative (g/kg body weight) food consumption were suppressed during the periods of gd 6 to 12, gd 15 to 19, and gd 6 to 19 (during dosing), but food consumption returned to control levels after the end of dosing. Body weight change was significantly reduced in the GLOX-treated animals during the period of gd 6 to 9, but no other effects on maternal body weight were observed. Necropsy of maternal animals revealed no treatment-related effect on maternal liver weight. GLOX exposure did not significantly alter post-implantation loss. GLOX had no effect on fetal body weight, or the incidence of external, visceral, or skeletal malformations.
In summary, maternal toxicity was manifested only as a transient reduction in body weight and food consumption at 50 mg/kg/day during the treatment period. No clear-cut evidence of developmental toxicity was observed at 50 mg/kg/day in the presence of mild maternal toxicity. This study suggests a no observed adverse effect level for maternal effects of ~50 mg/kg/day GLOX and a NOAEL of 50 mg/kg/day GLOX for developmental toxicity administered by gavage to pregnant NZW rabbits during organogenesis.