Combined effects of perfluorooctane sulfonate (PFOS) and maternal restraint stress on hypothalamus adrenal axis (HPA) function in the offspring of mice

Although it is known that prenatal exposure to perfluorooctane sulfonate (PFOS) can cause developmental adverse effects in mammals, the disruptive effects of this compound on hormonal systems are still controversial. Information concerning the effects of PFOS on hypothalamus adrenal (HPA) axis response to stress and corticosterone levels is not currently available. On the other hand, it is well established that stress can enhance the developmental toxicity of some chemicals. In the present study, we assessed the combined effects of maternal restraint stress and PFOS on HPA axis function in the offspring of mice. Twenty plug-positive female mice were divided in two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One half of the animals in each group were also subjected to restraint stress (30 min/session, 3 sessions/day) during the same period. Five plug-positive females were also included as non-manipulated controls. At 3 months of age, activity in an open-field and the stress response were evaluated in male and female mice by exposing them to 30 min of restraint stress. Male and female offspring were subsequently sacrificed and blood samples were collected to measure changes in corticosterone levels at four different moments related to stress exposure conditions: before stress exposure, immediately after 30 min of stress exposure, and recuperation levels at 60 and 90 min after stress exposure. Results indicate corticosterone levels were lower in mice prenatally exposed to restraint. In general terms, PFOS exposure decreased corticosterone levels, although this effect was only significant in females. The recuperation pattern of corticosterone was mainly affected by prenatal stress. Interactive effects between PFOS and maternal stress were sex dependent. The current results suggest that prenatal PFOS exposure induced long-lasting effects in mice.     

Interactions in developmental toxicology: concurrent exposure to perfluorooctane sulfonate (PFOS) and stress in pregnant mice

The maternal and developmental toxicity of combined exposure to restraint stress and perfluorooctane sulfonate (PFOS) was assessed in mice. On gestation Days 6-18, four groups of plug-positive female mice were orally exposed to PFOS at 0, 1.5, 3 and 6 mg/kg/day. Four additional groups of plug-positive animals received the same PFOS doses being restrained during 30 min three times per day. A control group was also included. Cesarean sections were performed on Day 18 of gestation and fetuses were weighed and examined for external, internal and skeletal malformations and variations. Before sacrifice of the dams, blood was collected and serum samples were prepared for thyroid hormones (total and free T3 and T4) and corticosterone analyses. The results of the present study show that both PFOS and restraint stress induced maternal toxicity. In turn, PFOS-induced fetal toxicity was evidenced by increased prenatal mortality. The only effect of restraint on fetal toxicity was a reduction on body weight and an increased prenatal mortality in fetuses concurrently exposed to 1.5 mg/kg of PFOS and restraint. PFOS-induced adverse effects on maternal and fetal toxicity in mice were observed at lower doses than those previously reported.     

Influence of maternal restraint stress on the long-lasting effects induced by prenatal exposure to perfluorooctane sulfonate (PFOS) in mice

The behavioral effects of concurrent maternal exposure to restraint stress and perfluorooctane sulfonate (PFOS) were assessed in the offspring of mice at 3 months of age. Plug positive females were divided into two groups. Animals were given by gavage 0 and 6mg PFOS/kg/day on gestation days 12-18. One-half of the animals in each group were subjected to restraint stress (30min/session, three sessions per day) during the same period. At 3 months, mice were evaluated for general activity in an open-field, and for learning and memory in a water maze task. The group prenatally exposed to PFOS and restraint presented a reduced mobility in the open-field. In the water maze, an interaction between sex and restraint was observed. Delayed task learning was also detected in females prenatally exposed to PFOS and restraint. An overall effect of restraint was observed in mice on retention of the task, suggesting a better retention in restrained animals. On the other hand, corticosterone levels were lower in animals prenatally subjected to restraint stress. The current results suggest interactive effects between PFOS and maternal stress.     

Concurrent exposure to aluminum and stress during pregnancy in rats: Effects on postnatal development and behavior of the offspring

The present study was conducted to assess the potential combined influence of maternal restraint stress and aluminum (Al) exposure on postnatal development and behavior in the offspring of exposed rats. Female rats were concurrently exposed to 0 (control group), 50 or 100 mg/kg/day of Al administered as Al nitrate nonahydrate in drinking water with citric acid (355 or 710 mg/kg/day) for a period of 15 days prior to mating with untreated males. Aluminum exposure was maintained throughout the gestational, lactational and post-weaning periods. On days 6-20 of gestation, one-half of the pregnant animals in each group were restrained for 2 h/day. Food consumption and maternal body weight were decreased in the groups exposed to restraint only or combined with the highest Al dose. All of the animals were allowed to deliver and wean their offspring. The pups were evaluated for physical development and neuromotor maturation. Moreover, open-field activity, passive avoidance, and spatial learning in a water maze were also determined on postnatal days 30, 35 and 60, respectively. Body weight of pups treated with 100 mg/kg/day of Al was decreased relative to controls from postnatal day 12 through 21, sexual maturation was delayed in Al treated females and in males exposed to 100 mg/kg/day. Forelimb grip strength was reduced in males exposed to 100 mg/Al/kg/day and in females exposed to this Al dose plus prenatal restraint. Learning in a passive avoidance task indicated facilitated performance for Al treated rats at 100 mg/kg/day combined with prenatal restraint as evidenced by longer avoidance latencies, while learning in a water maze task showed a shorter latency to find the platform on acquisition day 2 for Al treated rats. However, no effects of Al on water maze performance were detected during the retention probe trial in which the only effect noted was an increase in the platform quadrant swim time for the prenatal restraint group. In general terms, the results of the present study did not show a notable influence of maternal restraint on the Al-induced postnatal developmental and behavioral effects in the offspring of prenatally Al-exposed rats.     

Effects of prenatal exposure to manganese on postnatal development and behavior in mice: influence of maternal restraint

Manganese (Mn) is an essential trace element whose deficiency and excess have been reported to cause central nervous system (CNS) disturbances. On the other hand, during pregnancy, maternal stress has been shown to enhance the developmental toxicity of a number of metals. In this study, the maternal toxicity and developmental effects of a concurrent exposure to Mn and restraint stress were evaluated in mice. Pregnant animals were divided into three groups and received subcutaneous injections of manganese chloride tetrahydrate (MnCl2.4H2O) at 0, 1 and 2 mg/kg/day on Gestation Days 6-18. Each group was divided into two subgroups. Mice in one subgroup were subjected to restraint for 2 h/day on Days 6-18 of gestation. Pregnant mice were allowed to deliver, and pups were evaluated for physical and neuromotor maturation. Subsequently, adult mice were also evaluated for activity and learning. A significant increase in perinatal mortality was observed at 2 mg/kg/day Mn. A delay in some developmental landmarks (eye opening, testes descent) due to Mn exposure (2 mg/kg/day) was also seen in both restrained and unrestrained animals. No differences in motor resistance and coordination, or in learning at the passive avoidance test, were noted in adult mice. At the current Mn doses, combined exposure to Mn and stress during the prenatal period did not produce long-lasting effects on adult mice.     

Developmental neurotoxicity of organophosphorous pesticides: fetal and neonatal exposure to chlorpyrifos alters sex-specific behaviors at adulthood in mice.

Developmental exposure to the organophosphorous insecticide chlorpyrifos (CPF) induces long-term effects on brain and behavior in laboratory rodents. We evaluated in adult mice the behavioral effects of either fetal and/or neonatal CPF exposure at doses not inhibiting fetal and neonatal brain cholinesterase. CPF (3 or 6 mg/kg) was given by oral treatment to pregnant females on gestational days 15-18 and offspring were treated sc (1 or 3 mg/kg) on postnatal days (PNDs) 11-14. Serum and brain acetylcholinesterase (AChE) activity was evaluated at birth and 24 h from termination of postnatal treatments. On PND 70, male mice were assessed for spontaneous motor activity in an open-field test and in a socioagonistic encounter with an unfamiliar conspecific. Virgin females underwent a maternal induction test following presentation of foster pups. Both sexes were subjected to a plus-maze test to evaluate exploration and anxiety levels. Gestational and postnatal CPF exposure (higher doses) affected motor activity in the open field and enhanced synergically agonistic behavior. Postnatal CPF exposure increased maternal responsiveness toward pups in females. Mice of both sexes exposed to postnatal CPF showed reduced anxiety response in the plus-maze, an effect greater in females. Altogether, developmental exposure to CPF at doses that do not cause brain AChE inhibition induces long-term alterations in sex-specific behavior patterns of the mouse species. Late neonatal exposure on PNDs 11-14 was the most effective in causing behavioral changes. These findings support the hypothesis that developmental CPF may represent a risk factor for increased vulnerability to neurodevelopmental disorders in humans.     

Behavioral effects in adult mice exposed to perfluorooctane sulfonate (PFOS)

Nowadays, very little information concerning the effects on behavior in mammals of perfluorooctane sulfonate (PFOS), a widely distributed persistent environmental pollutant, is available. In the present study, we assessed the behavioral effects of PFOS on 3 months old mice after 1 month of exposure to this pollutant. Thirty adult mice were divided into three groups. Animals were given by gavage 0, 3, and 6 mg PFOS/kg/day for four consecutive weeks. After the treatment period, mice were evaluated for several skills by testing motor and sensory function by means of a functional observation battery (FOB), general activity and exploratory behavior in an open-field, and learning and memory in a water maze task. One week after behavioral testing, serum was collected for corticosterone analyses. No adverse effects were observed in the FOB. In general terms, activity in the open-field was similar in all groups being the only observed differences limited to the group given PFOS at 3mg/kg/day (spent less time in the center) and the group exposed to 6 mg PFOS/kg/day) (reduced rate of vertical activity). Concerning the effects of PFOS in the water maze, although all animals learned the task, no effect of the dose was observed during the acquisition. In the retention test, a deleterious effect of PFOS was noted. These results indicate that PFOS exposure induced only slight behavioral effects in adult male mice.     

Aluminum, restraint stress and aging: behavioral effects in rats after 1 and 2 years of aluminum exposure

Both aluminum (Al) and aging have been associated with neurobehavioral changes in mammals. In this study, the long-lasting neurobehavioral effects of prenatal restraint stress and oral Al exposure from conception to sacrifice were assessed in adult (1 year) and old (2 years) rats. Pregnant females were orally exposed to 0, 50, and 100 mg Al/kg/day. Each Al-exposed group was divided into two subgroups. One of this was subjected to restraint stress (2h/day on gestation days 6-20). The offspring of the treated females were maintained with the same Al treatment until sacrifice at 1 or 2 years of age. Activity in an open-field and learning in a water maze were evaluated. Although no significant differences were observed in motor activity, a biphasic effect of Al on learning could be observed. Thus, exposure to 100 mg Al/kg decreased performance of the task in both adult and old rats when compared to animals exposed to 50 mg Al/kg. An age-related effect on water maze performance, as well as an accumulation of Al in brain of rats exposed to 100 mg Al/kg at 2 years of age was found. Interestingly, while prenatal restraint stress did not modify behavioral parameters, Al accumulation was prevented by prenatal restraint.     

Prenatal or postnatal exposure to bis(tri-n-butyltin)oxide in the rat: postnatal evaluation of teratology and behavior

The results of a series of screening tests to determine the potential teratogenicity and neurotoxicity of developmental exposure to TBTO in rats are presented in this paper. For prenatal exposure, pregnant Long Evans rats were intubated with 0-16 mg/kg/day bis(tri-n-butyltin)oxide TBTO from Days 6 to 20 of gestation (GD 6-20). For postnatal exposure, rat pups were intubated with 0-60 mg/kg TBTO on Postnatal Day 5 (PND 5). Following prenatal exposure, dams were allowed to litter and pups were evaluated using a postnatal teratology screen. Postnatal evaluation for both exposures included motor activity (PND 13-64), the acoustic startle response (PND 22-78), growth, and brain weight. The maximally tolerated dose (MTD) in pregnant rats was 5 mg/kg/day, which is one-third the MTD in nonpregnant rats. There were decreased numbers of live births, and decreased growth and viability at dosages greater than or equal to 10 mg/kg/day. Cleft palate was found in 3% of the 12 mg/kg/day group. There was mortality following postnatal exposure to 60 mg/kg and all prenatal dosages greater than or equal to 10 mg/kg/day. Preweaning body weight was significantly decreased for all postnatal dosages, and all prenatal dosages greater than 2.5 mg/kg/day. Body weight reductions persisted to the postweaning period only in the high dose groups (10 mg/kg/day and 60 mg/kg). Behavioral evaluation demonstrated transient alterations in motor activity development (prenatal exposure only) and the acoustic startle response (postnatal exposure only). Persistent behavioral effects were observed only at dosages that produced overt maternal toxicity and/or postnatal mortality. The demonstration of the teratogenic and neurotoxic potential of TBTO in rats is confounded by associated maternal toxicity and/or pup mortality.     

Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations.

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.     

Restraint stress does not enhance the uranium-induced developmental and behavioral effects in the offspring of uranium-exposed male rats

The influence of stress on postnatal development and behavior was assessed in the offspring of male rats exposed to uranium (U). Eight groups of adult animals received uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 10, 20 and 40 mg/kg/day during 3 months. One half of rats in each group were concurrently subjected to restraint stress during 2 h per day throughout the study. At the end of the experimental period, male rats were mated with untreated females (1:2). On gestation day 14, one half of pregnant rats were euthanized in order to evaluate maternal toxicity and gestational parameters. The remaining dams were allowed to deliver and wean their offspring. Pups were evaluated for physical development, neuromotor maturation, as well as for behavioral effects. Restraint significantly increased the gravid uterine weight at 40 mg/kg/day. However, no significant interactions between restraint and U could be established in the remaining parameters of maternal toxicity. In the offspring, no remarkable effects of U, restraint or their combination were noted on developmental landmarks, or in the passive avoidance and water maze test. It is concluded that at the current U doses, restraint stress did not enhance the few uranium-induced physical, neuromotor and behavioral changes in the offspring of UAD-exposed male rats.     

Prenatal cocaine exposure: effects on locomotor activity in rat offspring

This study examines the developmental effects of prenatal exposure to cocaine in the rat, evaluated during the first month of life through open-field behavior. The offspring of Wistar dams that received 60 mg/kg of cocaine, from gestational day 8 to 22, were examined in the open-field during the second, third and fourth weeks of postnatal life in three consecutive 15-min daily sessions, starting on postnatal day (PND) 14, (PND 14–16), PND 21 (PND 21–23) and PND 28 (PND 28–30). Results show that prenatal exposure to cocaine increased total activity and rearing behavior on PND 22 and PND 29. Also, on PND 14, cocaine-exposed animals reared significantly more than control rats. There were no significant differences in the frequency of center and peripheral ambulation, nor in the defecation rate. The present results evidence alterations in the emotional behavior of rats prenatally exposed to cocaine. The delayed onset of exploration in the open-field observed in cocaine-exposed animals suggests that they take more time to become habituated to a novel and open environment.     

The Effect of Maternal Restraint on Developmental Toxicity of Aluminum in Mice

Both aluminum (Al) and maternal restraint have been reported to cause developmental toxicity in mammals. This study assessed in pregnant mice the potential interaction between Al and maternal restraint. Four groups of plug-positive female mice were given IP injections of AlCl₃ at 37.5 and 75 mg/kg/day on days 6–15 of gestation. Two of these groups were also subjected to restraint for 2 h/day during the same gestational days. Control groups included restrained and unrestrained pregnant mice nonexposed to Al. Cesarean sections were performed on gestation day 18, and the fetuses were weighed and examined for morphological defects. Maternal toxicity was significantly enhanced by restraint at 75 mg AlCl₃/kg/day. No increases in the number of resorptions or dead fetuses per litter were observed following exposure to Al, maternal restraint, or combined Al and restraint. However, a significant decrease in fetal body weight, as well as a significant increase in the number of litters with morphologic defects, was observed in the group exposed to 75 mg AlCl₃/kg/day plus maternal restraint. The current results suggest that maternal restraint could enhance the metal-induced developmental toxicity (reduced fetal body weight, increase in the number of litters with morphologic defects) only at high doses of the metal, which are also toxic to the dam.     

Prenatal exposure to benzodiazepine--I. Prenatal exposure to lorazepam in mice alters open-field activity and GABAA receptor function.

Prenatal exposure to benzodiazepines may lead to developmental abnormalities in humans and animals. To assess the behavioral and neurochemical effects of such exposure, pregnant mice were treated with lorazepam, 2 mg/kg/day, from days 13-20 of gestation, and open-field activity was assessed in offspring at 3 and 6 weeks of age and the function of GABAA receptors at 6 weeks of age. Activity was increased in mice exposed to lorazepam, compared to untreated or vehicle-treated controls at 3 weeks, but was unchanged at 6 weeks. Muscimol-stimulated uptake of chloride was decreased in lorazepam-treated mice, compared to controls, with a decrease in maximum uptake but no change in the EC50 for muscimol. Concentrations of lorazepam in maternal plasma and brain showed a similar brain:plasma ratio as previously reported and concentrations in fetal brain were about 50% of maternal levels. Lorazepam persisted for 48 hours after birth in dams but not in the offspring. These results indicate persistent behavioral and neurochemical alterations after prenatal exposure to lorazepam. This model may be useful in assessing other effects of prenatal exposure to benzodiazepine.     

Exposure of pregnant rats to uranium and restraint stress: effects on postnatal development and behavior of the offspring

The effects on postnatal development and behavior were assessed in the offspring of female rats concurrently exposed to uranium (U) and restraint stress. Adult female rats were administered uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 40 and 80 mg/(kg day) for 4 weeks before mating with untreated males, as well as during pregnancy and lactation. One-half of female rats in each group were concurrently subjected to restraint (2h/day). On gestation day 14, one-half of restrained and unrestrained rats were sacrificed in order to evaluate maternal toxicity and gestational parameters. Pups were evaluated for physical development, neuromotor maturation, and behavior. Uranium concentrations were also determined in various tissues of dams and fetuses. In all uranium-treated groups, the highest concentrations of this element were found in kidney and bone, being considerably higher than those in brain. Uranium levels in tissues of dam or fetuses were not significantly affected by restraint. No significant interactions between uranium and restraint could be observed in maternal toxicity. Moreover, no relevant effects of uranium, maternal restraint, or their combination were noted on developmental landmarks in the offspring. In the passive avoidance test, at 40 and 80 mg UAD/(kg day) restraint significantly modified passive avoidance acquisition (T1) and retention time (T2) 24h later. However, no significant differences were observed on the Morris water maze test. The results of the present study indicate that, in general terms, exposure of female rats to UAD before mating with untreated males, as well as during gestation and lactation, did not cause relevant dose-related adverse effects on postnatal development and behavior of the offspring. The influence of stress was very limited.     

Prenatal PFOS exposure induces oxidative stress and apoptosis in the lung of rat off-spring

Perfluorooctane sulfonate (PFOS) could induce neonatal pulmonary injuries in rodents. The aim of this study was to investigate the underlying mode of action. Pregnant rats were dosed orally with PFOS (0, 0.1 and 2.0mg/kgd) from gestation days (GD) 1 to 21. Lung samples from postnatal day (PND) 0 and 21 pups were analyzed for the toxic effects of PFOS. The results showed that maternal exposure to 2.0mg/kgd PFOS caused severe histopathological changes along with marked oxidative injuries and cell apoptosis in offspring lungs; at the same time, the ratio of Bax to Bcl-2, release of cytochrome c (Cyt c) from mitochondria to cytoplasm, expressions of Fas and Fas-L, and activities of caspase-3, -8 and -9 were up-regulated correspondingly. The results indicate that oxidative stress and both intrinsic and extrinsic cell death pathways were involved in prenatal PFOS exposure-induced injuries in postnatal lungs.     

Postnatal development and resistance to Plasmodium yoelii infection of mice prenatally exposed to triphenyltin hydroxide

In this study, we evaluated the effects of prenatal exposure to triphenyltin hydroxide (TPTH) on the postnatal development of Swiss Webster mice. Females were treated by gavage (0, 7.5 15 and 30 mg TPTH/kg/day) on days 6–17 of gestation. After birth, the progeny was examined for deaths, body weight gain and appearance of developmental landmarks. On postnatal day 50, one male and one female of each litter were inoculated with Plasmodium yoelii and the time‐course of infection was monitored. TPTH was embryolethal at doses ≥15 mg/kg/day. Body weight at birth was decreased, but no alteration of pup body weight was observed after postnatal day 5. Except for an advancement of incisor eruption in the group treated with 15 mg/kg/day, no alteration of somatic development was noted. A shorter latency to peak parasitemia and a reduced malaria‐induced spleen enlargement were observed in mice prenatally exposed to TPTH. In conclusion, prenatal exposure to TPTH at doses ≥15 mg/kg enhanced neonatal lethality, reduced pup birth weight and interfered with the response to infection with P. yoelii in adulthood. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.     

Combined action of uranium and stress in the rat. I. Behavioral effects

The influence of restraint stress on uranium (U)-induced behavioral effects was assessed in adult male rats. Eight groups of animals received uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 10, 20 and 40 mg/kg/day during 3 months. Rats in four groups were concurrently subjected to restraint during 2 h per day throughout the study. At the end of the period of uranium exposure, the following behavioral tests were carried out: open-field activity, passive avoidance and Morris water maze. Uranium concentrations in brain were also determined. At 10 and 20 mg/kg/day of UAD restraint significantly affected the total distance traveled in the open-field during the first and third periods tested, respectively, while no significant differences between groups were observed on the passive avoidance test. In the Morris water maze test, the influence of restraint was only significant on the latency time measured on Day 3 in rats exposed at 10 mg/kg/day. Restraint stress did not affect significantly the uranium levels in brain of rats. Although the results of the present study scarcely show uranium-induced behavioral effects at the oral doses of UAD here administered, these effects, as well as the slight influence of restraint stress noted in some tests should not be underrated.     

Developmental and neurobehavioral effects of perinatal exposure to polychlorinated biphenyls in mice

Because behavioral deficits associated with gestational exposure to polychlorinated biphenyls (PCBs) have been a concern, we studied the developmental and neurobehavioral effects of perinatal exposure to Aroclor 1254 (A1254), a commercial mixture of PCBs, in mice. The PCB mixture (A1254; 0, 6, 18, and 54 mg/kg body weight) was administered to pregnant mice (C57BL/6Cr) every 3 days by gavage from gestational day (GD) 6 to postnatal day (PND) 20. Compared with the control, treatment with A1254 did not alter the maternal body weight during the gestation and lactation periods. The body weight of the offspring did not differ among treatments. To assess the effects on offspring following such exposure, physical and neurobehavioral development (i.e., pinna detachment, hair growth, eye opening, incisor eruption, grasp reflex, righting reflex, walking, negative geotaxis, and cliff avoidance) was observed before weaning. At PND 7, poor adult-like responses in negative geotaxis were observed in all exposed groups. When the offspring were at 8-week old, the PCB-treated (18 mg/kg body weight) mice showed a decreased walking speed in the open-field test, and a prolonged time to reach the platform in the water maze test. Spontaneous locomotion activity was not affected by PCB exposure at 9 weeks . These results showed that perinatal exposure to PCBs produces several behavioral alterations in mice. Although dose-dependent changes were not observed, the neurobehavioral effects such as a decreased walking speed in the open-field test and a prolonged time to reach the platform in the water maze test remained in adulthood after the seeming recovery from the transient delay in development before weaning.