Foetotoxiciteit van methyleenblauw in de rat ; een verkennend onderzoek 199001001

Foetotoxiciteit van methyleenblauw in de rat ; een verkennend onderzoek

[ Fetotoxicity of methylene blue in the rat ; a pilot study ]

Piersma AH, Verhoef A, de Liefde A, van Nesselrooij BPM, Garbis-Berkvens JM

20 p in Dutch 1991

RIVM Rapport 199001001

Toon Nederlands

English Abstract
Several clinical centers have reported an increased incidence of intestinal atresias in twin pregnancies. In all cases only one infant of the twin appeared to be affected. A correlation has been suggested with the use of methylene blue. This dye is injected into one amniotic sac in order to discriminate between amniotic fluids of both conceptuses when amniocentesis is performed, around the 16th week of pregnancy. The etiology as well as the nature of these intestinal atresias are matters of dispute. The defect may be mediated by vascular effects, or by direct toxic effects on the intestinal epithelium after swallowing of amniotic fluid by the conceptus. We have investigated in a pilot study whether the rat provides an animal model for methylene blue induced intestinal atresias. Pregnant Riv:TOX rats were treated with methylene blue on day 16 p.c. by intraamniotic injection of 5 mul of 1 to 4% in water. The results showed no intestinal atresias at day 20 of pregnancy. However, an increased incidence of dead conceptuses and of cleft palate and digit malformations were found as a consequence of the operation procedure without exposure to methylene blue. Additional effects of methylene blue included high frequencies of dead conceptuses at 3 and 4% methylene blue. Clinically, 10 ml 1% methylene blue in water is injected in a total amniotic volume of around 200 ml. We injected 5 mul methylene blue solution in a total volume of 0.5 ml amniotic volume in the rat. Therefore, concentrations in the order of the clinically used dosage appear embryotoxic in the rat. The dosage used in clinical practice is high in view of the safety factor approach that requires at least a factor of 100 between no-effect-level in animal tests and dosages for human exposure.

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_{( 1991-03-31 )}