Teratogenic effect of ethylene glycol-methyl cellosolve mixture in rats: I: reproductive damage / Teratogénesis por etilenglicol-metilcelosolve en ratas: I: daño reproductivo

We investigated the reproductive damage and teratogenic effect of an ethylene glycol-methyl cellosolve mixture on gestating Wistar rats, which received a daily intraperitoneal dose of different concentration of the mixture on day 8 of gestation until day 20. In rats treated with the mixture the number of live fetuses decreased and reabsorptions increased with increasing concentrations of the mixture, as well as the number of abnormal fetuses. We conclude that the ethylene glycol-methyl cellosolve mixture possesses a higher teratogenic potential than each of its constituents separately, producing reproductive damage, external fetal abnormalities, growth delay, and increased fetal death.

Se investigó el daño reproductivo y efecto teratogénico de una mezcla de etilenglicol y metilcelosolve en ratas gestantes, las cuales recibieron por vía intraperitoneal una dosis diaria, a diferentes concentraciones de la mezcla, del día 8 al día 20 de gestación. En las ratas tratadas con la mezcla el número de fetos vivos disminuyó y las reabsorciones y el número de fetos anormales aumentaron a mayor concentración de los solventes. Concluimos que la mezcla de etilenglicol-metilcelosolve tiene mayor efecto teratogénico que cuando actúan cada uno de los solventes por separado, produciendo daño reproductivo, anormalidades fetales externas, retraso del crecimiento y aumento de muerte fetal.

Teratogenic effect of ethylene glycol-methyl cellosolve mixture in rats: II: craniofacial and limb abnormalities / Teratogénesis por etilenglicol-metilcelosolve en ratas: II: anormalidades craneofaciales y de miembros

We investigated the teratogenic effect of an ethylene glycol-methyl cellosolve mixture on gestating Wistar rats, that received a daily intraperitoneal dose of different concentration of the mixture on day 8 of gestation until day 20. Multivariate analysis and Post-Hoc Bonferroni tests were used and relative risk and attributable fraction were calculated. In rats treated with the mixture the number of live fetuses decreased and reabsorptions increased with increasing concentrations of the mixture, as well as the number of abnormal fetuses. Abnormalities consisted mainly in atypical craniofacial morphology, protruding tongue, edema, signs of growth delay and shorter limbs, their frequency and severity increased at higher concentrations of the mixture. We conclude that the ethylene glycol-methyl cellosolve mixture possesses a higher teratogenic potential than each of its constituents separately, producing external fetal abnormalities, growth delay, and increased fetal death.

Se investigó el efecto teratogénicos de una mezcla de etilenglicol y metilcelosolve en ratas gestantes, las cuales recibieron por vía intraperitoneal una dosis diaria, a diferentes concentraciones de la mezcla, del día 8 al día 20 de gestación. Se utilizaron las pruebas de análisis multivariado y Post-Hoc de Bonferroni, y se calcularon el riesgo relativo y la fracción atribuible. En las ratas tratadas con la mezcla el número de fetos vivos disminuyó y las reabsorciones y el número de fetos anormales aumentaron a mayor concentración de los solventes. Las anormalidades fetales consistieron principalmente en morfología atípica craneofacial, protrusión de la lengua, edema, signos de retraso de crecimiento y acortamiento de extremidades, y su frecuencia y severidad se incrementó a mayor concentración de la mezcla. Concluimos que la mezcla de etilenglicol-metilcelosolve tiene mayor efecto teratogénico que cuando actúan cada uno de los solventes por separado, produciendo anormalidades fetales externas, retraso del crecimiento y aumento de muerte fetal.

Chromosome Aberrations in Malformed Rat Fetuses Induced with Trypan Blue / 대한비뇨기과학회지

It is now well known that several human congenital syndromes are accompanied by chromosomal aberrations. Chromosomal aberrations can also be induced by several teratogenic agents in various species of animals when exposed to these agents at certain embryonic development (Installs et al.. 1963 ; Soukup et al., 1967 ; Joneja and Ungthavorn. 1968 ; Roux et al., 1970). A hereditary component in the etiology of urinary tract malformations has been reported in man and animals (Bagg. 1929 ; Deringer and Heston, 1956 ; Monie et al., 1957 ; Roux and Dupuis. 1961 ; Fujikura, 1969). The extent of hereditary influence. however, is difficult to in man, and even the major cause of congenital hydronephrosis is still unknown. The main purposes of this investigation is to determine whether trypan blue which induces congenital anomaly of urinary tract in rat embryos would also induce Chromosomal aberrations in the embryos and the mothers. Sprague-Dawley strain healthy female rats were examined for the spermatozoa in the vaginal smears everyday. Trypan blue solution 1.5% was injected subcutaneously with various doses at different developmental stages of rat embryos. For embryonic studies, the animals were killed on the 20th day of gestation. The total implantations, resorption rates and sex ratios were examined. Under the stereomicroscope. anomalies such as hydronephrosis, renal hypoplasia and agenesis, and anomaly of location. position and rotation of the kidney were examined through the micro-dissection method and confirmed histologically. For Chromosomal studies, the bone marrow cells of mothers and the liver cells of fetuses were examined cytogenetically by means of the culture method of Roux et al. (1970). From the data obtained, results were as follows; 1. Resorption of fetuses, growth retarding effects and chromosomal aberrations of fetuses were increased following the increased doses of trypan blue, but time of injection was more important in production of the malformations. 2. Following the increased doses of trypan blue and early injection, male fetuses were more produced. So it seemed that female fetuses were easily resorpted. 3. The timing of injection with trypan blue exerted greater influence upon the inducement of hydronephrosis than the doses of the chemical, but in cases of other malformations, vice versa. 4. In mothers chromosomal aberrations were related with the doses of the teratogen, but in fetuses, with the timing of injection. 5. So far as trypan blue is concerned, it is probable that there is a close relationship between chromosomal aberration and teratogenecity.