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Effects of zearalenone on in utero development in rats.
Food Chem Toxicol. 2006 Sep; 44(9):1455-65.FC

Abstract

Zearalenone (ZE), an estrogenic mycotoxin produced by Fusarium graminearum or F. roseum, is one of the most common contaminants of cereal grains world-wide. The objective of this study was to determine the effects of ZE on in utero development of rats. Pregnant female Charles River Sprague-Dawley rats were gavaged once daily with ZE (in corn oil) at doses of 0, 1, 2, 4, or 8 mg/kg body weight on gestation days (GD) 6-19. All females survived to cesarean section on GD 20. At cesarean section, reproductive and developmental parameters were measured and blood was taken for hormone analysis. Dose-related decreases were seen in maternal feed consumption and body weight gain in all treated groups. Delayed fetal development was linked to maternal toxicity. Fetal body weight was significantly decreased in both sexes in all treated groups. ZE retarded skeletal ossification at 4 and 8 mg/kg. Fetal anogenital index (anogenital distance normalized for body weight) was increased in all treated groups, indicating an androgenic effect of ZE during fetal development. Fetal viability was significantly decreased at 8 mg/kg; significant decreases were observed in number of viable fetuses, and number of litters totally resorbed. At 4 and 8 mg/kg, maternal liver-body weight ratios were significantly increased and organ-brain weight ratios for weights of liver, heart, spleen, kidneys, and ovaries were significantly decreased. Gonadotropins (LH, FSH, and prolactin) and sex steroids (progesterone and estradiol) were analyzed from the blood serum obtained at cesarean section. LH in the 0, 1, 2, and 4 mg/kg groups showed minimal variation, and slightly increased at 8 mg/kg. FSH was decreased in the 1, 2, and 4 mg/kg groups, but the level at 8 mg/kg was slightly higher than the control level. Prolactin level was not affected at 1 mg/kg, slightly increased at 2 and 4 mg/kg, and significantly increased at 8 mg/kg. Progesterone was decreased at 2, 4, and 8 mg/kg and the decreases were significant at 2 and 4 mg/kg. Estradiol level was not affected at 1mg/kg, but dose-related decreases were observed at 2, 4, and 8 mg/kg. Only the 8 mg/kg level of estradiol was significantly decreased. In summary, ZE was maternally toxic and fetotoxic but not teratogenic. The increased anogenital distance observed in male and female fetuses was considered a hormonal change rather than a teratologic response. The increased anogenital distance indicated an androgenic effect. Based on the dose-related maternal and fetal toxicity in all treated groups, the NOEL for reproductive and teratogenic effects was less than 1 mg/kg.

Authors+Show Affiliations

Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708, USA. tcollins@cfsan.fda.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16797818

Citation

Collins, Thomas F X., et al. "Effects of Zearalenone On in Utero Development in Rats." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 44, no. 9, 2006, pp. 1455-65.
Collins TF, Sprando RL, Black TN, et al. Effects of zearalenone on in utero development in rats. Food Chem Toxicol. 2006;44(9):1455-65.
Collins, T. F., Sprando, R. L., Black, T. N., Olejnik, N., Eppley, R. M., Alam, H. Z., Rorie, J., & Ruggles, D. I. (2006). Effects of zearalenone on in utero development in rats. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 44(9), 1455-65.
Collins TF, et al. Effects of Zearalenone On in Utero Development in Rats. Food Chem Toxicol. 2006;44(9):1455-65. PubMed PMID: 16797818.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of zearalenone on in utero development in rats. AU - Collins,Thomas F X, AU - Sprando,Robert L, AU - Black,Thomas N, AU - Olejnik,Nicholas, AU - Eppley,Robert M, AU - Alam,Hamida Z, AU - Rorie,James, AU - Ruggles,Dennis I, Y1 - 2006/05/11/ PY - 2006/01/30/received PY - 2006/04/14/revised PY - 2006/04/27/accepted PY - 2006/6/27/pubmed PY - 2006/9/29/medline PY - 2006/6/27/entrez SP - 1455 EP - 65 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem Toxicol VL - 44 IS - 9 N2 - Zearalenone (ZE), an estrogenic mycotoxin produced by Fusarium graminearum or F. roseum, is one of the most common contaminants of cereal grains world-wide. The objective of this study was to determine the effects of ZE on in utero development of rats. Pregnant female Charles River Sprague-Dawley rats were gavaged once daily with ZE (in corn oil) at doses of 0, 1, 2, 4, or 8 mg/kg body weight on gestation days (GD) 6-19. All females survived to cesarean section on GD 20. At cesarean section, reproductive and developmental parameters were measured and blood was taken for hormone analysis. Dose-related decreases were seen in maternal feed consumption and body weight gain in all treated groups. Delayed fetal development was linked to maternal toxicity. Fetal body weight was significantly decreased in both sexes in all treated groups. ZE retarded skeletal ossification at 4 and 8 mg/kg. Fetal anogenital index (anogenital distance normalized for body weight) was increased in all treated groups, indicating an androgenic effect of ZE during fetal development. Fetal viability was significantly decreased at 8 mg/kg; significant decreases were observed in number of viable fetuses, and number of litters totally resorbed. At 4 and 8 mg/kg, maternal liver-body weight ratios were significantly increased and organ-brain weight ratios for weights of liver, heart, spleen, kidneys, and ovaries were significantly decreased. Gonadotropins (LH, FSH, and prolactin) and sex steroids (progesterone and estradiol) were analyzed from the blood serum obtained at cesarean section. LH in the 0, 1, 2, and 4 mg/kg groups showed minimal variation, and slightly increased at 8 mg/kg. FSH was decreased in the 1, 2, and 4 mg/kg groups, but the level at 8 mg/kg was slightly higher than the control level. Prolactin level was not affected at 1 mg/kg, slightly increased at 2 and 4 mg/kg, and significantly increased at 8 mg/kg. Progesterone was decreased at 2, 4, and 8 mg/kg and the decreases were significant at 2 and 4 mg/kg. Estradiol level was not affected at 1mg/kg, but dose-related decreases were observed at 2, 4, and 8 mg/kg. Only the 8 mg/kg level of estradiol was significantly decreased. In summary, ZE was maternally toxic and fetotoxic but not teratogenic. The increased anogenital distance observed in male and female fetuses was considered a hormonal change rather than a teratologic response. The increased anogenital distance indicated an androgenic effect. Based on the dose-related maternal and fetal toxicity in all treated groups, the NOEL for reproductive and teratogenic effects was less than 1 mg/kg. SN - 0278-6915 UR - https://www.unboundmedicine.com/medline/citation/16797818/Effects_of_zearalenone_on_in_utero_development_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(06)00100-1 DB - PRIME DP - Unbound Medicine ER -