Developmental Toxicity of Glyoxal Trimeric Dihydrate (CAS No. 4405-13-4) in Sprague-Dawley (CD) Rats
Report Date: February 1994
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 the initiation of this study. GLOX (CAS No. 4405-13-4) was administered by gavage in water to mated CD rats (26 per group) on gestation days 6 through 15 at levels of 0, 50, 150, or 300 mg/kg/day. Animals were observed daily for clinical signs of toxicity. Mean food, water, and body weights were recorded for the animals in each group on gd 0, 3, 6, 9, 12, 15, 18, and 20. All animals in the developmental toxicity study were killed on gd 20 and examined for maternal body and organ weights, implant status, fetal weight, sex, and morphological development.
No maternal lethality occurred in this study, Pregnancy rates were 96%, 100%, 100%, and 89% in the control to high exposure groups, respectively. Changes in maternal body weight during the treatment period were smaller in the high dose group compared to the control group. Rooting behavior post-dosing was the clinical sign most frequently observed, primarily in the 150 and 300 mg/kg/day dose groups. Maternal food consumption (g/kg/day) was decreased in the high dose group during treatment on gd 6-12, and during the entire treatment period of gd 6-15, but not at other time points. Maternal water consumption (g/kg/day) following exposure (gd 15-20) was increased in a dose-related manner in all animals exposed to GLOX. Necropsy of the maternal animals revealed no dose-related effects on liver weight. In utero GLOX exposure did not affect the frequency of post-implantation loss, mean fetal body weight per litter, or external, visceral, or skeletal malformations.
In summary, maternal toxicity was manifested as only a slight reduction in maternal body weight and food consumption at 300 mg/kg/day during the treatment period. Thus, no observed adverse effect level for maternal toxicity was 300 mg/kg/day GLOX. No developmental toxicity was observed at doses as high as 300 mg/kg/day. This study established a NOAEL for developmental toxicity in the presence of mild maternal toxicity of greater than or equal to 300 mg/kg/day administered by gavage to pregnant CD rats during organogenesis.