ethylenethiourea and Abnormalities--Drug-Induced

The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea.. Female rats were exposed to ethylenethiourea on the 11(th) day of pregnancy (experimental group) or to 0.9% physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively.. Muscle and skeletal abnormalities were observed in 100%, anorectal anomalies in 86%, absent tail in 71%, short tail in 29%, duodenal atresia in 5%, esophageal atresia in 5% and persistent omphalomesenteric duct in 5%. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract.. Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.

Topics: Abdominal Muscles; Abnormalities, Drug-Induced; Animals; Animals, Newborn; Digestive System Abnormalities; Disease Models, Animal; Ethylenethiourea; Female; Fetus; Ganglia; Interstitial Cells of Cajal; Muscular Atrophy; Myenteric Plexus; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Rats; Rats, Wistar; Staining and Labeling; Statistics, Nonparametric

The aim of this study was to study the effect of vitamin A deficiency (VAD) on the embryological development of anorectal malformations (ARMs) and the enteric nervous system.. Female Sprague-Dawley rats were divided into 3 groups: VAD group, normal group (negative control), and ethylene thiourea (ETU) group (positive control) with a normal diet. On day 20 of pregnancy, cesarean section was performed on all rats. The incidence of ARMs in the fetal rats and Protein gene product 9.5 (PGP9.5) and S-100 protein expression by immunohistochemistry were determined.. The incidence of ARMs in VAD and ETU groups was 64.8% (59/91) and 45.9% (61/133), respectively (P > .05). Anorectal malformations were not found in the normal group. Protein gene product 9.5 and S-100 protein expression in the non-ARM rectums of the VAD group was lower than the ETU (P = .0156 vs P = .0105) and normal groups (P = .0091 vs P = .0024). There was no significant difference in PGP9.5 and S-100 protein expression between ETU and normal groups. In the ARM rectums, PGP9.5 and S-100 protein expression in the VAD group was lower than the ETU group (P < .0001). Protein gene product 9.5 and S-100 protein expression was also lower in ARM than non-ARM rectums in the VAD and ETU groups (P < .0001, P = .0203, and P = .0122, respectively).. Vitamin A deficiency during pregnancy may result in the embryological development of ARMs. Enteric nervous system development may be related to ARMs.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Anal Canal; Animals; Anus, Imperforate; Diet; Enteric Nervous System; Ethylenethiourea; Female; Gene Expression Regulation, Developmental; Nerve Tissue Proteins; Neurons; Pregnancy; Pregnancy Complications; Random Allocation; Rats; Rats, Sprague-Dawley; Rectum; S100 Proteins; Tail; Teratogens; Ubiquitin Thiolesterase; Vitamin A; Vitamin A Deficiency

The embryologic and pathologic aspect of anorectal malformation (ARM) remains poorly understood. There is no universally accepted theory to explain anorectal embryology and the abnormal development that produces ARM. The aim of this study was to observe the developmental processes of anorectum in rats and to explore the abnormal embryonic development that leads to ARM.. Rat embryos with ARM were obtained by treating pregnant rats with administration of ethylenethiourea (ETU). Normal rat embryos and embryos with ARM from gestational days 12.5 to 20 were sectioned serially and sagittally and stained with H & E. The relevant structure including cloaca and urorectal septum (URS) were examined in a temporospatial sequence.. Characteristics of anorectum development in ARM rat embryos treated by ETU were as follows: (1) URS never fused with cloaca membrane. (2) Dorsal cloacal membrane was maldeveloped. (3) Cloacal configuration was abnormal. (4) Tail groove never appeared. All type of ARM was the rectourethal fistula and common cloaca in ETU-treated rat embryos and was discernible on gestation day 16.. Absence of the tail groove and maldevelopment of the dorsal cloacal membrane, cloacal configuration, and urorectal septum are likely to be responsible for the formation of ARM. Failure of fusion of the URS with cloacal membrane is the immediate reason for rectourethral fistula or common cloaca in ETU-treated rats.

Topics: Abnormalities, Drug-Induced; Anal Canal; Animals; Cloaca; Ethylenethiourea; Female; Gestational Age; Morphogenesis; Pregnancy; Rats; Rectal Fistula; Tail; Teratogens; Urethra; Urethral Diseases; Urinary Fistula

Lumbosacral vertebral abnormalities are a common association of anorectal malformations (ARMs) and are one of the determinants of the eventual level of fecal continence that can be achieved. This study used a fetal rat model to investigate the spectrum of axial skeletal maldevelopment that may occur with ARMs. Time-mated pregnant rats received 125 mg/kg of 1% ethylenethiourea (ETU) (experimental group) or vehicle only (control). Their fetuses were examined for external malformations and prepared for staining of their skeletons using Alcian blue and Alizarin red S. ARMs developed in 67/68 (98%) of ETU-exposed fetuses, of which 28 (42%) also developed rachischisis, mainly involving the lumbosacral vertebrae. No skeletal abnormality was found in control fetuses. ETU-exposed fetuses with ARMs and rachischisis had abnormal ossification of the vertebral centrum, abnormal fusion between the neural arches of vertebrae, localized narrow or interrupted thoracic vertebral canal, a widely open vertebral canal in the lumbosacral area (rachischisis), and absence of the lower two sacral and coccygeal vertebrae. Rib abnormalities included absence of two to three floating ribs, abnormal fusion of adjacent proximal segments, and abnormal ramification, irregularity, and angulation of their distal segments. The vertebral and rib abnormalities found in ETU-exposed fetuses with ARMs but no rachischisis were much less severe. In addition to the lumbosacral anomalies that are common with ARMs, severe abnormalities of the thoracic vertebrae and their corresponding ribs may occur also. Fetuses with both ARM and rachischisis tend to have more extensive and severe vertebral and rib anomalies. These observations imply a possible common aetiology for ARMs and vertebral anomalies and are consistent with our understanding of the perceived role of the notochord in axial development.

Topics: Abnormalities, Drug-Induced; Anal Canal; Animals; Disease Models, Animal; Ethylenethiourea; Female; Fetus; Lumbar Vertebrae; Notochord; Osteogenesis; Pregnancy; Rats; Rats, Sprague-Dawley; Rectum; Ribs; Sacrum; Spinal Canal; Spinal Dysraphism; Thoracic Vertebrae

Considerable public concern has developed regarding possible adverse reproductive outcomes resulting from exposure to power frequency magnetic fields (MF). To identify possible effects of MF exposure on fetal development, timed-pregnant female Sprague-Dawley rats (55/ group) received continuous exposure to linearly polarized, transient-free 60 Hz MF at field strengths of 0 Gauss (G; sham control), 0.02 G, 2 G, or 10 G, or intermittent (1 hr on/1 hr off) exposure to 10 G fields. Dams received MF or sham exposures for 18.5 hr/day on gestation days 6 through 19. A positive control group of 15 dams received daily oral doses of 85 mg ethylenethiourea (ETU)/kg body weight on gestation days 11, 12, and 13; positive control dams received no MF exposure. Ambient and experimentally generated MF were monitored continuously throughout the study. Experimentally generated MF were within 2% of the target field strengths at all times, and ambient MF to which sham controls were exposed did not exceed 0.7 mG at any point in the study. No evidence of maternal toxicity was identified in any MF-exposed dam; mean maternal body weight and organ weights in groups exposed to MF did not differ from those in sham controls. Comparisons of fetal viability and body weight demonstrated no biologically significant differences between MF-exposed groups and sham controls. Similarly, a battery of gross external, visceral, skeletal, and cephalic examinations demonstrated no significant differences in the incidence of fetal malformations or anomalies in MF-exposed groups vs. sham controls. By contrast, 100% of the fetuses in the positive control group treated with ETU demonstrated malformations and reduced body weight. Exposure of pregnant Sprague-Dawley rats to 60 Hz at field strengths up to 10 G during gestation days 6-19 did not produce biologically significant effects in either dams or fetuses. These results do not support the hypothesis that exposure to pure, linearly polarized 60 Hz MF is a significant risk factor for the developing fetus.

Topics: Abnormalities, Drug-Induced; Abnormalities, Radiation-Induced; Animals; Body Weight; Bone and Bones; Brain; Electromagnetic Fields; Embryonic and Fetal Development; Ethylenethiourea; Female; Male; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction

Pregnant Sprague Dawley rats were separated into two groups. In the experimental group, single intragastric doses of ethylenethiourea (ETU) were given on the 11th day of gestation. In the control group, a single intragastric dose of distilled water was given on the same day of gestation. Fetuses were recovered on day 20 of gestation, and were prepared for dissection and light microscopy. A high incidence of axial dysraphic disorders (omphalocele and rachischisis) and imperforate anus with recto-urethral fistula were noted in experimental male rat fetuses obtained from dams subjected to varying doses of ETU.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Animals; Anus, Imperforate; Ethylenethiourea; Female; Fetal Diseases; Hernia, Umbilical; Lumbosacral Region; Male; Pregnancy; Rats; Rats, Sprague-Dawley; Spinal Dysraphism

A literature review of individual pregnancies and recent surveys involving large cohorts reveal an association between congenital malformation and maternal hyperthyroidism, suggesting that some aspect of hyperthyroidism or its treatment might compromise the development of the fetus. Experiments have shown that the thyroid antagonist, ethylenethiourea (ETU), causes fetal malformations when administered to pregnant rats, but it is not known whether it is ETU or the imbalance in maternal thyroid hormone which it causes which is the teratogenic agent. Here we employ in vitro culture to determine the possible direct effects on rat embryos of two thyroid antagonists, ETU and methimazole (MMI), the latter being one which is used for treatment of thyrotoxicosis in humans. It was found that ETU can compromise the development of rat embryos in vitro, confirming that ETU has a direct effect on the rat embryo. It was also found that MMI can cause abnormal development of rat embryos in vitro, although the concentration at which MMI disturbs rat embryogenesis is higher than that which is reached in hyperthyroid patients treated with clinical doses of MMI or carbimazole.

Topics: Abnormalities, Drug-Induced; Animals; Embryo, Mammalian; Ethylenethiourea; Hyperthyroidism; Imidazoles; In Vitro Techniques; Methimazole; Rats; Rats, Inbred Strains

Embryos were studied either after direct exposure to ethylenethiourea (ETU) during incubation of embryo cultures or after maternal ETU dosing and subsequent embryonic development in utero with a view to assess the similarity of these two systems to produce hydrocephalus. Ten-day-old rat embryos were incubated with nutrient media containing 0-2.0 mM of ETU in a constant gasseous environment following a newly modified method. The cultured embryos showed hydrocephalus in the form of dilated rhombencephalon and other anomalies at the 1.5 and 2.0 mM of ETU after 26 hours of incubation. No anomalies were seen in the control group. In in vivo studies, dilated rhombencephalon or hydrocephalus was not observed when dams, orally dosed with ETU on gestation day 10, were either killed daily for three postdosing days to examine embryos or killed at term to evaluate fetuses. This discrepancy in dilatation that was incidental to the rhombencephalon in the two systems pointed out that the fourth ventricle of the cranial neural tube responded by dilatation in vitro but remained unaffected in vivo following ETU exposure. ETU dosing of dams on the 12th day of pregnancy, when embryos are known to be sensitive to ETU-induced hydrocephalus, followed by serial gross examination of embryos, suggested that edema occurred in a generalized form but only after the appearance of both hydrocephalus (dilatation primarily in mesencephalon) and, the previously reported, neuroblastic necrosis.

Topics: Abnormalities, Drug-Induced; Animals; Embryo, Mammalian; Environment, Controlled; Ethylenethiourea; Female; Gases; Gestational Age; Hydrocephalus; Imidazoles; Maternal-Fetal Exchange; Pregnancy; Rats; Rats, Inbred Strains

Pregnant Sprague-Dawley rats were utilized in this study. They were separated into two groups. In the control group, a single intragastric dose of distilled water was given on the 11th day of gestation. In the test group, a single intragastric dose of ethylenethiourea (ETU), 240 mg/kg was given on the same day of gestation. Embryos were recovered 12, 24, 36, and 48 hours after ETU and distilled water administration, and were prepared for scanning electron microscopy and light microscopy. The posterior neuropore of rat fetuses in the control group closed completely on gestation day 12.5. However, the closure of posterior neuropore in ETU-induced fetuses is shown to have been disrupted 12 hours after ETU administration. Marked neural tissue overgrowth in the posterior neuropore resulted in neural fold eversion and finally produced a picture of lumbosacral myeloschisis on day 13 of gestation. Our observation implies that myeloschisis is induced by non-closure of the neural fold, not by reopening after its proper closure.

Topics: Abnormalities, Drug-Induced; Animals; Ethylenethiourea; Female; Microscopy, Electron, Scanning; Neural Tube Defects; Pregnancy; Rats; Rats, Inbred Strains; Spinal Cord

We have demonstrated that ethylenethiourea (ETU) is a potent teratogen to the rat embryo developing in vitro. Sprague Dawley rat embryos were explanted on gestation day 10 and cultured for 48 hours in the presence of 40-200 micrograms/ml ETU. This resulted in a dose-related inhibition of growth and differentiation as assessed by crown-rump length, protein and DNA content, and somite number and in an increase in the frequency of abnormalities. A variety of anomalies was produced, including fluid accumulation in the brain (hydrocephalus), decreased mandibular size, decreased telencephalon size, abnormal dorsiflexion, as well as subectodermal blisters on the tail and limb buds and maxilla. Frank malformations have been observed at these same sites--hydrocephalus, brachygnathia, kyphosis, limb and tail defects, cleft palate--in the term fetus in vivo. The presence of abnormal fluid accumulation in the embryos--distended neural tube and subectodermal blisters--suggesting that the osmotic environment of the embryo had been altered by ETU exposure. Osmolality of the exocoelomic fluid (ECF) surrounding the embryo was measured after 48 hours of exposure to a concentration of ETU that caused nearly a 100% incidence of subectodermal blisters. ECF osmolality was found to be significantly lower than that of control embryos. Lowered osmolality would cause water to move out of the ECF, presumably causing the observed fluid accumulation in the embryo. It is speculated that altered osmotic balance and localized edema in the embryo are contributory steps in the formation of defects after ETU exposure.

Topics: Abnormalities, Drug-Induced; Animals; Ectogenesis; Edema; Ethylenethiourea; Extracellular Space; Female; Imidazoles; In Vitro Techniques; Pregnancy; Rats; Teratogens; Water-Electrolyte Balance

Ethylenethiourea (ETU) is a degradation product from ethylenebisdithiocarbamate such as Zineb and Maneb which have been extensively used in food crops and ornamental plants. Khera (1973, 1975, 1977) reported that administration of ETU to pregnant rats could induce anomalies in the visceral organs and the central nervous system of fetuses in food toxicology. From this point, in an attempt to better understand the pathomechanism of teratogenesis in the central nervous system, we have studied the effects of ETU on the central nervous system of rat fetuses. In this study, pregnant Sprague Dawley (SD) rats were used and subjected to ETU. Various types of congenital malformations of the central nervous system are presented in rat fetuses including spinal dysraphism associated with hindbrain crowding, exencephaly, meningoencephalocele, microencephaly, hydraencephaly and hydrocephalus. Each depended on the gestation days of the ETU administration and dosages.

Topics: Abnormalities, Drug-Induced; Animals; Central Nervous System; Ethylenethiourea; Female; Fetus; Imidazoles; Injections; Pregnancy; Rats; Stomach

The science of teratology is discussed from a regulatory point of view. A brief history of this branch of toxicology is presented with emphasis on specific instances of the inadvertent production of birth defects in humans as a result of exposure to exogenous agents. The basic principles of teratology are elucidated as a means of understanding current test protocols and their scientific rationale. A typical, general protocol is given and some of the major shortcomings of such a bioassay are presented. Among these shortcomings are the problems of significance of fetal toxicity and lack of a postnatal component to the teratology test system. The teratogenic and/or fetotoxic potential of selected pesticides are examined with special reference to the bioassay problems alluded to. Pesticides discussed include cacodylic acid, endrin, benomyl, ETU, nitrofen, and mirex. Finally, a brief discussion of a proposed teratology screen using pregnant laboratory animals is presented.

Topics: Abnormalities, Drug-Induced; Animals; Benomyl; Cacodylic Acid; Drug Evaluation, Preclinical; Endrin; Ethylenethiourea; Female; Humans; Mirex; Pesticides; Phenyl Ethers; Pregnancy; Teratogens

66 pregnant rats were divided into 9 groups according to gestation day 11 to 19. These pregnant rats were subjected to a single intragastric administration of ethylenethiourea (ETU) and cesarian sectioned on day 20. No dam died following the ETU treatment, but the rate of fetal death was as high as 21.2% on day 11, followed by a gradual decrease in the fetal death rate thereafter. The rate of production of various types of externally visible malformations was 100% except in the fetuses of dams treated with ETU on gestation day 19. The important results were as follows. (I) Fetuses of dams treated with ETU from gestation day 11 were found to suffer from a high incidence of myeloschisis associated with hindbrain crowding. (II) Exencephaly and an abnormally enlarged head with occipital bossing due to herniation of the mesencephalic tectum, with and without dilatation of the mesencephalic and 4th ventricle, were induced among the fetuses of dams given ETU at gestation day 12 and 13. (III) Various degrees of hydranencephaly and dysgenic hydrocephalus were found among the fetuses of dams treated with ETU from gestation days 14 to 18. The above results suggest that ETU may be a useful agent for the production of congenital malformations in the rat.

Topics: Abnormalities, Drug-Induced; Animals; Arnold-Chiari Malformation; Brain; Central Nervous System; Ethylenethiourea; Female; Imidazoles; Maternal-Fetal Exchange; Pregnancy; Rats; Rats, Inbred Strains; Spinal Cord

Time-mated Swiss-Webster mice were pretreated in separate experiments with phenobarbital (60 mg/kg X d sc on d 7-10 of pregnancy), SKF-525A (40 mg/kg ip on d 12 of pregnancy) or 3-methylcholanthrene (20 mg/kg X d on d 10-12 of pregnancy). On the d 12 of pregnancy (1 h after SKF-525A or 3-methylcholanthrene treatment), one group each of pretreated mice was given a single oral dose of 1600, 2000, or 2400 mg/kg of ethylenethiourea (ETU) as a 5% concentrate in a 1.5% aqueous gelatin solution, which as a vehicle was given to other pretreated groups. The respective volume doses were 3.2, 4.0, or 4.8 ml/100 g body weight with the controls given 4.8 ml/100 g body weight of vehicle alone. Maternal toxicity was observed in all groups given ETU, whether pretreated with metabolic modifiers or not. In the three experiments, treatment with ETU alone reduced fetal weight by 15% at 2400 mg/kg and 8% with the remaining 2 doses, and increased the incidence of resorptions (19-62% with the 2400 mg/kg dose, 8-59% at 2000 mg/kg, and 7-32% at the 1600 mg/kg dose). The significant defects with incidence ranges in three experiments were: hindpaw ectrodactyly, 2-6% at 1600 mg/kg, 4-20% at 2000, and 20-29% at 2400 mg/kg; and hindpaw syndactyle, 3% at 16 mg/kg, 6-14% at 2000, and 2-12% at 2400 mg/kg doses. Minor incidences of cleft palate and hindpaw polydactyly were also observed. Phenobarbital pretreatment did not change the ETU-induced maternal or fetal effects. SKF-525A enhanced the resorptions and reduced the litter-size but had no effect on fetal malformations. The 3-methylcholanthrene pretreatment reduced the ETU-induced incidences of hindpaw ectrodactyly, hindpaw syndactyly, and cleft palate at the 2000 and 2400 mg/kg doses. Previous studies with rats and hamsters revealed that SKF-525A enhanced the ETU-induced fetal malformations but phenobarbital and 3-methyl-cholanthrene had no effect in these two species.

Topics: Abnormalities, Drug-Induced; Animals; Cytochrome P-450 Enzyme System; Ethylenethiourea; Female; Foot Deformities, Congenital; Hindlimb; Imidazoles; Methylcholanthrene; Mice; Phenobarbital; Pregnancy; Proadifen; Species Specificity

Nitrites are present in a wide variety of foods and their daily intake in man has been estimated at 1.5 mg. Ethylenethiourea (ETU), a major food contaminant resulting from degradation of ethylenebisdithiocarbamate fungicides, is a potent rat teratogen. The co-administration of ETU (60 or 40 mg/kg) and NaNO2 (80 mg/kg) to rats by gavage on day 15 of gestation resulted in a higher survival of progeny than occurred with the corresponding dose of ETU alone. In a second study, ETU (60 mg/kg) and NaNO2 (80, 100 or 120 mg/kg) were administered, either individually or in combination, as a single dose on day 13 of gestation. Administered alone, NaNO2 did not produce any teratogenic response in full-term foetuses, whereas ETU produced a high incidence of various anomalies. However, the combined dosing resulted in the elimination of almost all the anomalies. The reducing effect of NaNO2 on ETU-induced malformations was reversed when the animals were pretreated with 200 mg ascorbic acid/kg or 360 mg sodium ascorbate/kg. Since both of these are well-known inhibitors of N-nitrosation reactions, it was presumed that the simultaneous oral dosing of ETU and NaNO2 resulted in the formation of N-nitrosoethylenethiourea.

Topics: Abnormalities, Drug-Induced; Animals; Ascorbic Acid; Drug Interactions; Ethylenethiourea; Female; Imidazoles; Nitrites; Pregnancy; Rats; Rats, Inbred Strains; Sodium Nitrite

Teratogenic potential of ethylenethiourea (ETU) was investigated in SLC-ICR mice after its reaction with sodium nitrite. ETU was given orally in doses of 400 mg/kg on various days of pregnancy in combination with 200 mg/kg NaNO2 at varied intervals. When NaNO2 was given to females immediately after their treatment with ETU on day 6 or 8 of pregnancy, fetal survival was significantly decreased. Various types of malformations were observed in the living fetuses from mothers treated on day 6, 8, or 10 of pregnancy, but not on day 12. The teratogenicity disappeared when NaNO2 was given 2 h after the treatment with ETU.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Animals; Drug Synergism; Ethylenethiourea; Female; Fetal Death; Fetus; Gestational Age; Imidazoles; Lung; Mice; Nitrites; Pregnancy; Sodium Nitrite; Time Factors

The hygienic significance of the studies on pesticides from the aspect of their "long-term" effects upon the individual and the generations are emphasized. The basic methods and approaches used in the Laboratory of long-term effects with chemical etiology at the IHOH, Sofia, are discussed, namely for detecting the changes in gonads, reproduction and generation, embryotoxic and teratogenic effects, and changes in cardiovascular system. The results are discussed, namely: fundasol--the effect on gonads, generations, embryotoxic and teratogenic effects, changes in the cardiovascular system; endodan--changes in gonads, reproduction, embryotoxicity; basfungin--embryotoxic and teratogenic effects. All of these studies were performed for the purpose of threshold levels, establishment hygienic standardisation and prognosis of the potential risk for human.

Topics: Abnormalities, Drug-Induced; Animals; Benzimidazoles; Cardiovascular System; Dose-Response Relationship, Drug; Embryo, Mammalian; Ethylenethiourea; Female; Fungicides, Industrial; Imidazoles; Liver; Male; Mice; Pregnancy; Rats; Reproduction; Sulfides; Thiazoles; Thiocarbamates; Time Factors; Zineb

Topics: Abnormalities, Drug-Induced; Animals; Ethylenethiourea; Female; Fetus; Imidazoles; Pregnancy; Rats; Zinc

The potential of the fungicide maneb and two of its metabolites, ethylenebisisothiocyanate sulfide (EBIS) and ethylene thiourea (ETU), to induce perinatal toxicity in four species of rodents was investigated. The compounds were admininistered to rats and mice during the period of organogenesis, and ETU was also administered to rats and mice during the period of organogenesis, and ETU was also administered by oral gavage for a similar period to hamsters and guinea pigs. Treatment also continued through the lactational period in groups of rats that were allowed to give birth. Fetuses were examined for signs of toxicity, including terata, and neonates for reflex developement and open-field behavior. Maneb produced hydrocephalus in fetuses in litters of rats receiving 480 mg/kg . d. No fetotoxic effects were noted in litters of rats receiving EBIS at doses at high as 30 mg/kg . d. ETU proved to be a potent teratogen in the rat. Among the effects seen at doses of 40 mg/kg . d or greater were hydrocephalus, encephalocele, kyphosis, and various defects of the digits. Neither maneb (up to 1500 mg/kg . d), ETU (up to 200 mg/kg . d), nor EBIS (up to 200 mg/kg . d) elicited signs of fetal toxicity in the mouse. ETU also failed to result in fetal toxicity when administered to the hamster (100 mg/kg . d) or the guinea pig (100 mg/kg . d). Neither maneb nor EBIS produced significant dose-related alterations in the behavioral development of perinatally exposed rat neonates. At doses that also produced neonatal hydrocephalus, ETU produced significant increases in the open-field activity of the neonates. In addition to the perinatal effects noted above, both maneb and EBIS caused maternal limb paralysis in the rat, an effect not noted in the mouse at much higher doses.

Topics: Abnormalities, Drug-Induced; Animals; Behavior, Animal; Cricetinae; Ethylenethiourea; Female; Fetus; Gestational Age; Guinea Pigs; Imidazoles; Maneb; Mesocricetus; Mice; Pregnancy; Rats; Species Specificity; Thiocarbamates; Thiocyanates

Topics: Abnormalities, Drug-Induced; Animals; Ataxia; Cats; Cleft Palate; Coloboma; Dose-Response Relationship, Drug; Ethylenethiourea; Female; Gestational Age; Hernia, Umbilical; Imidazoles; Paralysis; Pregnancy; Pregnancy, Animal; Spina Bifida Occulta; Teratogens

Topics: Abnormalities, Drug-Induced; Animals; Carcinogens; Environmental Exposure; Ethylenethiourea; Female; Fetal Diseases; Gestational Age; Goiter; Imidazoles; Male; Myxedema; Neoplasms; Pregnancy; Rats; Teratogens; Thyroid Neoplasms