Evaluation of heart malformations in B6C3F1 mouse fetuses induced by in utero exposure to methyl chloride

C57BL/6 female mice impregnated by C3H males mice to produce B6C3F1 fetuses were exposed daily for six hr to atmospheres containing 0, 250, 500, or 750 ppm methyl chloride, from gestation day 6 to gestation day 18. There were 74 to 77 females with copulation plugs per exposure concentration. Females exposed to 750 ppm ethyl chloride exhibited ataxia commencing on the seventh day of exposure (gestation day 12). They also showed hypersensitivity to touch or sound, tremors and convulsions. Six females in the 750 ppm group died and one was euthanized in extremis prior to scheduled sacrifice. On gestation day 18, all other females were euthanized for evaluation. Only dams exposed to 750 ppm exhibited significant decrease in body weight by gestation day 18, weight gain during the gestation period, and absolute weight gain (weight gain minus gravid uterine weight) versus controls. There were no treatment related-effects on these parameters in the other exposure groups. None of the groups exhibited exposure-related differences in pregnancy rate, gravid uterine weight, or maternal liver weight. There were no differences in the numbers of implantations, resorption, dead fetuses, nonlive (dead plus resorbed) fetuses, live fetuses, sex-ratio, or mean fetal body weight per litter. There was a significant exposure-related increase in the number and percentage of affected (nonlive plus malformed) fetuses per litter with the incidence of affected fetuses in the 750 ppm group significantly higher than controls. There was a statistically significant increase in the incidence of heart defects in the 500 and 750 ppm group relative to controls. Of the 37 fetuses in the study with heart defects, 23 were females, 14 were males. The heart defects observed included: absent or abnormal tricuspid valve, reduced number of papillary muscles and/or chordae tendineae on the right side, small right ventricle, globular heart, and white spots in the left ventricular wall. Multiple malformations were observed in one fetus from the 500 ppm group and in three fetuses in the 750 ppm group. It is concluded that methyl chloride inhalation exposure to pregnant C57BL/6 mice from gestation day 6 through gestation day 17 resulted in maternal toxicity only at the 750 ppm exposure concentration and was teratogenic to B6C3F1 conceptuses at exposure concentrations of 750 and 500 ppm, leading to fetal heart malformations. No evidence of embryo or fetotoxicity other than teratogenicity was seen at any of the exposure concentrations employed. No maternal, embryo or fetotoxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 250 ppm of methyl chloride.     

Growth and development of mice offspring after irradiation in utero with 2,450-MHz microwaves

Mice offspring irradiated in utero with 2,450-MHz radio-frequency (RF) radiation at 0 or 28 mW/cm2 (whole-body averaged specific absorption rate = 0 or 16.5 W/kg) for 100 minutes daily on days 6 through 17 of gestation were evaluated for maturation and development on days 1, 5, 10, 12, 15, and 17 of age. The tests used to determine differences in developmental age in the two treatment groups were body weight, urine concentrating ability, brain weight, tolerance to ouabain, and bone lengths. Fifteen sham-irradiated and 26 RF-irradiated litters, normalized to eight pups/litter, were used in this study. Mean body weight of the microwave-irradiated offspring were significantly (p = .0003) decreased only on day 1 of age. Brain weight on days 10, 12, and 17 were significantly lower in microwave-irradiated pups (p = .01). There were no significant differences in the two groups in urine concentrating ability on day 5, ouabain tolerance on day 15, or bone length on days 5, 10, 12, and 17. It is concluded that there is a persistent delay in postnatal development of the brain after RF irradiation with 16.5 W/kg during gestation.     

Spacing of fetuses and local competition in strains of mice with large, medium and small litters.

The tendency for fetuses to be evenly spaced along the uterine horn and the relationship of this to local competition between fetuses was examined in three strains of mice which characteristically produce large, medium and small litters. Local competition was assessed by correlating, within each uterine horn, the weight of each fetus or placenta with the mean distance to its immediate neighbours. Weights and distances were measured on day 19 of gestation, on the day before expected parturition and distances only on day 7. Average litter sizes (live fetuses) were 16.3 +/- 0.9, 11.7 +/- 0.6 and 7.2 +/- 0.5 (mean +/- SEM) in the large, medium and small litter strains, respectively (n = 7, 7 and 10, respectively). On day 19, the mean distance between fetuses was significantly less (P < 0.05) in the large strain (10.1 +/- 1.0 mm) than in the medium (14.0 +/- 1.2 mm) or small (13.5 +/- 1.0 mm) strains. Evenness of spacing, expressed as the standard deviation of distances between fetuses divided by the mean distance, improved from day 7 to day 19 of gestation in all three strains and effectively prevented local competition between fetuses in the medium litter (r = 0.04) and small litter strains (r = 0.17), but not in the large litter strain (r = 0.45, P < 0.01). Thus, local crowding does not seem to be detrimental to fetal growth in mice, except in strains specifically bred for large litters.     

Studies of the effect of 0.4-Gy and 0.6-Gy prenatal X-irradiation on postnatal adult behavior in the Wistar rat

Thirty-four pregnant Wistar rats were X-irradiated on the 9th or 17th day of gestation at a dosage level 0.4 Gy or 0.6 Gy or were sham-irradiated. All mothers were allowed to deliver their offspring, and litters were limited to a maximum of eight on day 2. On day 30, 224 offspring were weaned and raised until 60 days of age, at which time testing began. Each rat randomly received, in random order, three of the following six behavioral tests: Water T-maze, Conditioned Avoidance Response, Forelimb Hanging, Activity Wheel, Swimming, and Open Field. There were no statistically significant differences between the irradiated and control groups for maternal weight or weight gain or mean litter size, although the litter size of the 17th day 0.6-Gy group was slightly lower. Among offspring irradiated with 0.6 Gy on the 17th day, 3-day-old neonates' weights were significantly reduced. Offspring irradiated on the 17th day with 0.6 Gy exhibited higher Conditioned Avoidance Response 5th-day and retest avoidance scores than did the controls. There were also significant sex differences in responses within the irradiated and control groups for several tests, which were unrelated to radiation exposure. The results of this study indicate that low-level X-irradiation during the fetal period of rat gestation results in neonatal growth retardation and subtle behavioral alterations that may be manifested in adult life. Growth retardation may be the most sensitive indicator of subtle effects that result from low-level prenatal exposure to X-rays.     

Effects of AET and MEA treatment of mice on the first day of pregnancy

Porton female mice were injected intraperitoneally with 2-aminoethylisothiouronium bromide hydrobromide (AET) or cysteamine hydrochloride (MEA) in a dose of 40 mg/kg of body weight on the first day of pregnancy. On the last, nineteenth, day of gestation, taking into consideration females in whose uterus live fetuses were observed, the increase in their body weight throughout pregnancy, the number of fetuses in the uterus, the body weight of fetuses, and placental weight were found smaller in mice treated with AET or MEA, than in control ones. Among the injected compounds, AET appeared to be less toxic than MEA.     

Embryotoxicity of oral administered chlorothalonil in mice

BACKGROUND: Chlorothalonil (2,4,5,6-tetrachloroisophthalonitril), the nephrotoxic fungicide, was examined for its potential to produce developmental toxicity in mice after oral administration. METHODS: Pregnant ICR (CD-1) mice were given sublethal doses of 0 (corn oil), 100, 400, and 600 mg/kg/day chlorothalonil by gavage on gestation days (GD) 6-15. RESULTS: Maternal effects in 400 and 600 mg/kg/day dose groups included signs of toxicity such as weakness and depression in the maternal activity, and reduction in body weight and weight gain. No maternal toxicity was apparent in the 100 mg/kg/day dose group. Maternal exposure to chlorothalonil during organogenesis significantly affected the number of live fetuses, early resorption, and mean fetal weight in the 400 and 600 mg/kg/day dose groups. No external, visceral, and skeletal abnormalities were observed among any of the treated groups compared to the control. CONCLUSIONS: On the basis of the present results chlorothalonil can produce clinical signs of toxicity and fetotoxicity without teratogenic effects at 400 and 600 mg/kg/day dose groups.     

Developmental toxicity of orally administered 2',3'-dideoxycytidine in mice

2',3'-Dideoxycytidine (DDC), a potent inhibitor of human immunodeficiency virus (HIV), is presently undergoing clinical trials as a promising anti-AIDS drug. Since there are very limited published animal toxicity data available, and nucleoside analogues are being considered for treatment of HIV-infected pregnant women, a study was conducted in mice to investigate the potential adverse developmental effects of this drug. DDC, suspended in 0.5% methyl cellulose, was administered via gavage twice per day during gestation days (gd) 6 through 15 to C57Bl/6N mice in a total dose of 0, 200, 400, 1,000, or 2,000 mg/kg/day. Maternal weight gain during the gestation and treatment period, as well as gravid uterine weight, decreased significantly in the 2,000 mg group, but weight gain, corrected for gravid uterine weight, was not affected by DDC. The percent resorptions per litter increased significantly in the highest dose group, and there were fewer live litters because of complete litter resorption in six dams. Among litters with live fetuses, the mean litter size was significantly reduced in the 2,000 mg group. Average fetal body weight per litter decreased significantly in the 1,000 and 2,000 mg groups. The number of fetuses with any malformation, the number of litters with one or more malformed fetuses and the percent of malformed fetuses per litter increased significantly in the 1,000 and 2,000 mg groups. There was an increase in malformations at 400 mg/kg/day; however, it was not statistically significant. In conclusion, DDC produced developmental toxicity (malformations, reduced fetal body weight, and resorptions) in the absence of overt maternal toxicity except for body weight changes due to resorptions and reduced fetal weights.     

An examination of respiratory distress and chromosomal abnormalities in the offspring of male mice treated with ethylnitrosourea

A functional defect (respiratory distress), in addition to morphological defects, was induced in the offspring of male ICR mice treated with ethylnitrosourea (ENU) before mating. ENU (100 and 50 micrograms/g) was injected intraperitoneally into adult male ICR mice that were then mated with untreated females. After the cesarian operation on the 18th day of gestation, fetuses were resuscitated. In the apneic fetuses showing respiratory distress, the lung was collapsed and the ductus arteriosus was not closed. The incidence of fetuses showing respiratory distress was significantly increased with the high dose (100 micrograms/g) of ENU, and it was higher after spermatogonial exposure than after postmeiotic exposure. There was no linearity in the dose-response relationship at the lower dose (50 micrograms/g), as was the case with the specific-locus mutation. The frequency per microgram ENU of fetuses showing respiratory distress was 3.7 X 10(-4) for spermatogonial treatment (calculated at a dose of 100 micrograms/g), the value being about 10-20 times higher than that of ordinary mutations in mice. About half of the fetuses showing respiratory distress often had specific anomalies (dwarfism and gigantic thymus), but the remainder showed no morphological changes. Spermatogonial treatment produced a zero or very low incidence of translocations in the meiotic configurations of primary spermatocytes. G-band analysis of the affected F1 fetuses also revealed no visible chromosomal abnormalities (there could be small deletions or inversions) except that trisomy 19 was found in a dwarf fetus.     

The effect of prenatal photoperiodic history on the postnatal endocrine status of female lambs

Postnatal photoperiodic experience plays a pivotal role in determining the timing of ovarian activity in female lambs. This study examines whether a photoperiodic history gained while in utero is able to influence this timing.Pregnant Soay ewes were maintained in either long days (n = 7, 18 h light : 6 h dark; group PLD) or short days (n = 12, y h light : 18 h dark; group PSD) from 25 days of gestation. At birth, female lambs (n = 8 per group) were transferred to long days for 10 weeks, and then placed under short days until the end of the experiment at 38 weeks of age. Blood samples were collected from lambs on the day of birth and three times weekly for the duration of the study and the resulting plasma assayed for progesterone and prolactin.Although both gestational photoperiods produced, at best, abbreviated periods of ovarian activity, lambs born to ewes which experienced long days during gestation (group PLD) exhibited elevated plasma progesterone concentrations significantly earlier (P < 0.05) than lambs born to ewes exposed to short days during gestation (group PSD) (mean ± SEM, 193 ± 17 versus 244 ± 14 days for PLD and PSD groups, respectively. Plasma prolactin concentrations in newborn lambs born between late December and early April were not affected by the ambient photoperiod, but reflected the artificial daylength experienced by their mothers during gestation. Lambs born to ewes maintained under long days during gestation (group PLD) had significantly higher prolactin concentrations on the day of birth than lambs born to ewes maintained under short days during gestation (group PSD) (45 ± 5.4 ng/ml versus 7 ± 3.7 ng/ml respectively, P < 0.001). The mean birth weight, rate of live weight gain and live body weight of lambs at the end of the experiment did not vary significantly between treatment groups. These results suggest that the ovine foetus is sensitive to photoperiodic information prior to birth, and develops a photoperiodic history which, under the present experimental conditions, modulates the subsequent endocrine status of the neonatal lamb.     

Teratogenicity of Asparagus racemosus Willd. root, a herbal medicine

Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.     

Adaptive response in embryogenesis: II. Retardation of postnatal development of prenatally irradiated mice.

We previously reported that a priming dose of 0.3 Gy on gestation day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations caused by exposure to 5 Gy X rays on gestation day 12 in ICR mice. In the present study, postnatal development of the live offspring was investigated using a set of developmental and behavioral parameters. The offspring of the mice irradiated with 0.3 Gy generally showed a delay in the appearance of most of the physiological markers, impaired acquisition of neonatal reflexes, and alteration of adult behavior. However, an increase in body weight in the females was observed 4 weeks postnatally. In the offspring primed with 0.3 Gy followed by a challenging dose of 5 Gy prenatally, a high postnatal mortality was found, and all the survivors had various radiation-induced detrimental effects. The results indicated that the priming dose was advantageous to survival itself, but was disadvantageous to the health of survivor. The results also suggested that studying the whole animal can show the extent of the effects of radiation, i.e. quality of life, in a way that cellular or molecular studies cannot.     

Effect of early shearing during gestation on the productive and reproductive behavior of female sheep offspring in their first 18 months of age

The research has shown the interesting contributions of shearing in mid-gestation on the performance of lambs from birth to weaning. Other studies have reported that shearing at early pregnancy influences the development of the placenta and lamb live weight at birth. However, there was a lack of information on the effect of early-prepartum shearing on the behavior of the offspring from weaning onward. This study evaluated the effect of shearing ewes at 50 days of gestation on the growth, reproductive behavior and response to a gastrointestinal parasite challenge in the female offspring from weaning to 18 months old. Fifty-seven Polwarth female lambs were used, 22 being singles and 35 twins born to ewes either shorn at 50 days of pregnancy (PS, n = 23) or shorn at 62 days postpartum (U, control, n = 34) resulting in four subgroups: single lambs born to PS ewes (n = 8), born to U ewes (n = 14), twin lambs born to PS ewes (n = 15) or born to U ewes (n = 20). All progeny were managed together under improved pasture with a minimum forage allowance of 6% live weight on dry basis. Body weight, body condition score and fecal eggs count were recorded every 14 days from weaning to 18 months of age. Concentrations of progesterone were measured weekly (from 4 to 10 months of age and from 14 to 18 months of age) to establish the onset of puberty. Ovulation rate at an induced and a natural heat (545 ± 1.0 and 562 ± 1.0 day old) was recorded. Prepartum shearing did not affect the age at puberty or the ovulation rate of female offspring, but those born as singles were more precocious ( P = 0.03) and heavier ( P = 0.02) at puberty than twin born lambs. Both the average value of parasite egg count ( P = 0.0 7) and the Famacha index ( P = 0.02) for the entire study period were lower in lambs born to prepartum shorn ewes than those born to postpartum shorn ewes. In conclusion, shearing at 50 days of gestation did not affect the growth or the reproductive behavior of female offspring. However, female lambs born from ewe shorn during gestation showed a better response to the parasitic challenge, and further research is required to confirm this.     

Retinoic-acid-induced limb-reduction defects: perturbation of zones of programmed cell death as a pathogenetic mechanism

Pregnant C57Bl/6J mice were treated with 100 mg/kg body weight of all-trans retinoic acid in sesame oil on day 11.0 of gestation. Among the live fetuses harvested on day 18 of gestation, 100% had mesomelic defects of the limbs as determined by gross examination and skeletal staining. Control fetuses treated with sesame oil had no observable limb malformations. Some treated and control embryos were harvested 12 hr after treatment and examined for patterns of cell death by using the supravital stain Nile blue sulphate and methylene-blue- and acid-fuchsin-stained histological sections. Retinoic-acid-induced cell death in the core of the limb was always associated with the zones of programmed cell death as seen in control embryos of comparable stages. This, in concert with previous studies demonstrating excessive cell death in regions of programmed cell death that correlated with subsequent malformations, leads us to conclude that the pathogenesis of mesomelic malformations has a primary association with the phenomenon of programmed cell death.     

Effects of dinocap on otolith development: evaluation of mouse and hamster fetuses at term

The morphology of otoliths in CD-1 mouse and Syrian hamster fetuses exposed to the fungicide dinocap were evaluated at the end of gestation. Pregnant mice were dosed by gavage with 0, 10, 15, 30, or 60 mg/kg/day dinocap in corn oil on days 7-16 of gestation. Pregnant hamsters were dosed by the same route with 0, 50, 100, or 200 mg/kg/day on days 7-14 of gestation. At the end of gestation (day 18 in mice, day 15 in hamsters) dams were killed and all fetuses were removed and fixed overnight in 70% ethanol. Fetal heads were then removed, left in 70% ethanol for at least 3 days, and then dehydrated in a graded ethanol series and cleared with methyl salicylate. Otoliths were examined by darkfield microscopy, and each otolith was scored for morphological completeness on a scale of 0 to 3. Otolith development was complete by day 18 of gestation in control mouse fetuses. Otolith development was complete in many, but not all, of the hamster fetuses by day 15 of gestation. In the mouse, dinocap exposure inhibited fetal otolith formation in a dose-related manner, with a significant effect on total otolith score occurring at 10 mg/kg/day and above. Dinocap affected otolith formation in the hamster only at 100 mg/kg/day (200 mg/kg/day was embryolethal), concomitant with severe maternotoxicity and fetotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Embryonic survival in mice treated with AET, MEA or 5-HT on the first day of pregnancy

The embryotoxicity of AET, MEA, and 5-HT was investigated in Porton mice. Female mice on the first day of gestation were injected intraperitoneally with 2-amino-ethylisothiouronium bromide hydrobromide (AET), cysteamine hydrochloride (MEA) or serotonin-creatinine sulphate (5-HT) in a dose of 40 mg/kg body weight. Uterine contents were examined on the nineteenth day of pregnancy. As compared with controls, in mice treated with AET, MEA or 5-HT, a smaller number of live fetuses and a greater number of non-implanted embryos, resorptions, and dead fetuses were found. Not all females which were injected with these compounds had live fetuses. Among the compounds, MEA appeared to be more toxic than AET and 5-HT.     

Influence of formaldehyde and Sonacide (potentiated acid glutaraldehyde) on embryo and fetal development in mice

Pregnant outbred albino mice were given formaldehyde or Sonacide (potentiated acid glutaraldehyde) by gavage on days 6--15 of gestation. The mice were killed on day 18, the general health and reproductive status of the dam evaluated, and the fetuses examined and processed in order to characterize external, visceral, and skeletal malformations. Although formaldehyde (stock solution containing 12--15% methanol as a preservative) was lethal to 22 of 34 dams treated with 185 mg/kg/day, and one of 35 dams treated with 148 mg/kg/day, these doses did not produce statistically significant (two-sided p < 0.05 versus controls) teratogenic effects in the fetuses of the surviving dams. Sonacide was also judged not to be teratogenic to the mice employed in this study, in spite of the fact that relatively high doses were employed. The highest doses of Sonacide studied (5.0 ml/kg/day, which is equivalent to 100 mg/kg/day of glutaraldehyde) killed 19 of 35 dams and caused a significant reduction in the mean weight gain of the surviving mothers. In addition, this dose produced a significant increase in the number of stunted fetuses.     

Effect of prenatal exposure to diagnostic ultrasound on the development of mice.

Pregnant Swiss albino mice were exposed to diagnostic ultrasound (3.5 MHz, approximately 65 mW) for 10 min on Day 3.5 (preimplantation period), 6.5 (early organogenesis period), or 11.5 (late organogenesis period) of gestation. Sham-exposed controls were maintained for comparison. Exposed as well as control fetuses were dissected out on the 18th day of gestation, and changes in total mortality, body weight, body length, head length, brain weight, sex ratio, and microphthalmia were recorded. Exposure on Day 3.5 of gestation resulted in a small increase in the resorption rate and a significant reduction in fetal body weight. A low fetal weight and an increase in the number of growth-retarded fetuses were produced by exposure on Day 6.5 postcoitus. A statistically nonsignificant increase in the incidence of microphthalmia was induced in fetuses exposed on Day 6.5 or Day 11.5 of gestation. These results indicate that ultrasound may have some adverse effects on the mouse embryos depending on the developmental stage at which the exposure occurred.     

Effect of dietary arginine supplementation on reproductive performance of mice with porcine circovirus type 2 infection

The objective of this study was to investigate whether supplemental dietary arginine increases reproductive performance in mice infected with porcine circovirus type2 (PCV2). A total of 50KM female mice were allotted randomly to the arginine group (0.6% arginine?+?gestation diet) and control group (1.22% alanine?+?gestation diet). All the mice began to mate after 14?days of treatment with our prepared feed and challenged with PCV2 at the dose of 100 TCID₅₀ (50% tissue culture infection dose, TCID₅₀) after 7?days of pregnancy. Abortion rate, litter number, litter birth weight, the daily weight gain in the first 7?days and survival rate in the first 2?weeks of the neonates were calculated. The serum progesterone, estrogen, nitric oxide and superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) on the 14th day of pregnancy were measured. Arginine supplementation decreased the abortion rate of pregnant mice and mortality of neonates caused by PCV2 infection. Further, litter number, litter birth weight and the daily weight gain of neonates increased in the arginine group compared to the control group. Arginine supplementation increased significantly the serum progesterone (P?<?0.01) and nitric oxide levels (P?<?0.05), but had little effect on the serum estrogen level. SOD activity and T-AOC in the arginine group were significantly higher (P?<?0.01) than the control group. In conclusion, arginine supplementation partially reversed the reproductive failure in mice caused by PCV2 infection.     

Effects of prenatal X-irradiation on the 14th-18th days of gestation on postnatal growth and development in the rat

Thirty-nine pregnant adult Wistar strain rats were randomly assigned to one of three exposure groups: 0, 0.75, or 1.50 Gy X-radiation total exposure. Animals were exposed from the 14th to the 18th days of gestation at 0, 0.15, or 0.30 Gy per day. At term, 15 rats were killed and morphologic analyses were completed. Twenty-four rats were allowed to deliver their offspring. On the first day of postnatal life, litters were reduced to a maximum of eight pups per litter, with equal numbers of male and female offspring wherever possible. A total of 187 pups were observed for the age of acquisition of five reflexes (air righting, surface righting, visual placing, negative geotaxis, auditory startle) and the appearance of four physiologic markers (pinna detachment, eye opening, vaginal opening, testes descent). There was significant dose-related weight reduction in term fetuses and offspring throughout the 86-day postnatal period. Postnatal growth rate (g gained/day) was unaffected. Adult offspring brain and gonadal weight and organ weight:body weight ratios were reduced. Using the PAC50 methodology, dose-related alterations occurred in the acquisition of several reflexes. All physiologic markers exhibited a dose-related delay in appearance. These results indicate that fractionated exposure to X-radiation during the fetal period in the rat results in dose-dependent alterations in postnatal growth and physiologic development. These studies are important for our understanding of the long-range effects of prenatal exposure to ionizing radiation late in gestation.     

Lack of teratogenicity of aluminum hydroxide in mice

The embryotoxic and teratogenic potential of aluminum hydroxide, a therapeutic drug used as an antacid and phosphate binder, was investigated in Swiss mice. Mated female mice were given by gavage daily doses of 0, 66.5, 133 or 266 mg/kg of A1 (OH)3 on gestation days 6 through 15 and killed on gestation day 18. Females were evaluated for body weight gain, food consumption, appearance and behavior, survival rates, and reproduction data. No significant effects attributable to A1(OH)3 were noted in comparison of maternal body weight and food consumption values, appearance and behavior. No treatment-related changes were recorded in the number of total implants, resorptions, the number of live and dead fetuses, fetal size parameters or fetal sex distribution data. Gross external, soft tissue and skeletal examination of the A1-treated fetuses did not reveal differences at any dose in comparison with the controls. Thus, no evidence of maternal toxicity, embryo/fetal toxicity or teratogenicity was observed with A1(OH)3 in mice.