Reproductive and neurobehavioural toxicity study of tartrazine administered to mice in the diet.

Tartrazine was given in the diet to provide levels of 0% (control), 0.05%, 0.15%, and 0.45% (approximately 83, 259, 773 mg/kg/day, respectively) from five weeks of age of the F0 generation to nine weeks of age of the F1 generation in mice, and selected reproductive and neurobehavioural parameters were measured. In movement activity of exploratory behaviour in the F0 generation, number of vertical activity was significantly increased in the middle-dose group in males. There were no adverse effects of tartrazine on either litter size, litter weight and sex ratio at birth. The average body weight of male offspring was significantly increased in the high-dose group and that of female offspring was significantly increased in the middle-dose group at birth. In behavioural developmental parameters, surface righting at PND 4 was significantly accelerated in the high-dose group in male offspring, and those effects were significantly dose-related in a trend test (P<0.01). Cliff avoidance at PND 7 was significantly accelerated in the middle-dose group in male offspring. Negative geotaxis at PND 4 was significantly delayed in the high-dose group in female offspring. Other variables measured showed no significant adverse effects in either sex in the lactation period. In movement activity of exploratory behaviour in the F1 generation, number of movement showed a significant tendency to be affected in the treatment groups in male offspring in a trend test (P<0.05). The dose level of tartrazine in the present study produced a few adverse effects in neurobehavioural parameters during the lactation period in mice. Nevertheless, the high-dose level were in excess of the ADI of tartrazine (0-7.5 mg/kgbw), and the actual dietary intake of tartrazine is presumed to be much lower. It would therefore appear that the levels of actual dietary intake of tartrazine is unlikely to produce any adverse effects in humans.     

Reproductive and neurobehavioural effects of bis(2-ethylhexyl) phthalate (DEHP) in a cross-mating toxicity study of mice.

Bis(2-ethylhexyl) phthalate (DEHP) was given in the diet to provide levels of 0% (C) or 0.03% (T) from 5 weeks of age of the F0 generation to 9 weeks of age of the F1 generation in mice. At 9 weeks of age, each female was paired with one male from the same or another treatment groups (cross-mating: C/C, T/C, C/T, T/T), for a period of 5 days. The selected reproductive and neurobehavioural parameters were measured. There were no adverse effects of DEHP on either litter size, litter weight and sex ratio at birth. The average body weight of female offspring was significantly affected in group IV (T/T) at PND 14. In behavioural developmental parameters, swimming direction at PND 4 was significantly accelerated in group III (C/T) in female offspring. In movement activity of exploratory behaviour at 3 weeks of age, number of movement of male offspring was significantly affected in group IV (T/T). The dose level of DEHP in the present cross-mating study produced few adverse effects in reproductive and neurobehavioural parameters in mice.     

Reproductive and neurobehavioural toxicity study of bis(2-ethylhexyl) phthalate (DEHP) administered to mice in the diet.

Bis(2-ethylhexyl) phthalate (DEHP) was given in the diet to provide levels of 0 (control), 0.01, 0.03, and 0.09% from 5 weeks of age of the F0 generation to 9 weeks of age of the F1 generation in mice, and selected reproductive and neurobehavioural parameters were measured. There were no adverse effects of DEHP on either litter size, litter weight or sex ratio at birth. The average body weight of male offspring was significantly decreased in the low-dose group at birth. In behavioural developmental parameters, surface righting at PND 4 was significantly delayed in the low- and middle-dose group in female offspring, and those effects were slightly dose related (P < 0.05). Surface righting at PND 7 was significantly depressed in the high-dose group of male offspring, and those effects were significantly dose related (P < 0.001). That of female offspring was significantly depressed in the low-dose group. The dose level of DEHP in the present study produced few adverse effects in reproductive and neurobehavioural parameters in mice.     

Effects of litter size on behavioral development in mice

The effect of litter size on behavioral development was investigated in 1384 offspring from 114 litters of CD-1 control mice. Litters were classified in four groups of size: 5 to 7 (I), 8 to 10 (II), 11 to 13 (III), and 14 to 17 (IV). Group III was regarded as the control group. The offspring were examined for behavioral development including surface righting at Postnatal Days (PND) 4 and 7, negative geotaxis at PNDs 4 and 7, cliff avoidance at PND 7, swimming behavior at PNDs 4 and 14, and olfactory orientation at PND 14. In behavioral development, surface righting at PND 7 was significantly affected in group I. Swimming direction at PND 4 was significantly affected in group IV, and those effects showed significant tendencies to be retarded as litter size increased. Other measured parameters showed no significant effect of litter size.     

Reproductive and neurobehavioural toxicity study of Ponceau 4R administered to mice in the diet.

Ponceau 4R was given to mice in the diet at levels of 0 (control), 0.12%, 0.24%, and 0.48% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(1) generation, and selected reproductive and neurobehavioural parameters were measured. There was no adverse effect of Ponceau 4R on litter size, litter weight or sex ratio at birth. The average body weight of male and female offspring was increased significantly in the high-dose group at postnatal days (PNDs) 0, 4 and 21. In behavioural developmental parameters, surface righting at PND 4 was affected significantly in the high-dose group in male offspring. Other variables measured showed no consistently significant adverse effect on either sex in the lactation period. In multiple water T-maze performance in the F(1) generation, the time taken was significantly longer than the control in the middle-dose and high-dose groups in males, and those effects were significantly dose-related (P<0.01). The dose level of Ponceau 4R in the present study produced no adverse effect on reproduction, and a few adverse effects on neurobehavioural parameters in mice. The non-observed adverse effect level (NOAEL) was presumed to be 0.12% in the diet (approximately 205mg/kg per day) for maze learning by males in the F(1) generation. Nevertheless, the middle-dose and high-dose levels were in excess of the acceptable daily intake (ADI) of Ponceau 4R (0-4.0mg/kg body weight), and the actual dietary intake of Ponceau 4R in humans is presumed to be much lower. It would appear, therefore, that the level of dietary intake of Ponceau 4R is unlikely to produce any adverse reproductive or neurobehavioural effect in humans.     

Neurobehavioral toxicity study of dibutyl phthalate on rats following in utero and lactational exposure

To investigate the neurobehavioral effects of dibutyl phthalate (DBP), an important endocrine disruptor known for reproductive toxicity, on rodent offspring following in utero and lactational exposure, pregnant Wistar rats were treated with DBP (0, 0.037, 0.111, 0.333 and 1% in the diet) from gestation day (GD) 6 to postnatal day (PND) 28, and selected developmental and neurobehavioral parameters of the offspring were measured. There were no significant effects of DBP on body weight gain of the dams during GD 6–20 or on the pups' ages of pinna detachment, incisor eruption or eye opening. Exposure to 1% DBP prolonged gestation period, decreased body weight in both male and female pups, depressed surface righting (PND 7) in male pups, shortened forepaw grip time (PND 10), enhanced spatial learning and reference memory (PND 35) in male pups. Exposure to 0.037% DBP also shortened forepaw grip time (PND 10), but inhibited spatial learning and reference memory in male pups. Sex × treatment effects were found in forepaw grip time (PND 10), spatial learning and reference memory, and the male pups appeared to be more susceptible than the females. However, all levels of DBP exposure did not significantly alter surface righting (PND 4), air righting (PND 16), negative geotaxis (PND 4 or 7), cliff avoidance (PND 7) or open field behavior (PND 28) in either sex. Overall, the dose level of DBP in the present study produced a few adverse effects on the neurobehavioral parameters, and it may alter cognitive abilities of the male rodent. Copyright © 2009 John Wiley & Sons, Ltd.     

Reproductive and neurobehavioural toxicity study of erythrosine administered to mice in the diet.

Erythrosine was given in the diet to provide levels of 0 (control), 0.005, 0.015 and 0.045% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(1) generation in mice, and selected reproductive and neurobehavioural parameters were measured. There were no adverse effects of erythrosine on either litter size, litter weight or sex ratio at birth. The average body weight of the offspring was significantly increased in the middle-dose group in both sexes during the lactation period. In behavioural developmental parameters, any variables showed no significant adverse effects in either sex in the lactation period. In movement activity of exploratory behaviour, several parameters were significantly changed in the high-dose group, and those effects were dose related in adult females in the F(0) and F(1) generations and in male offspring in the F(1) generation. The dose level of erythrosine in the present study produced few adverse effects in reproductive and neurobehavioural parameters in mice.     

Repeated in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure affects male gonads in offspring, leading to sex ratio changes in F2 progeny

The effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the reproductive system of male rat offspring (F1) and the sex ratio of the subsequent generation (F2) were examined. Female Holtzman rats were gavaged with an initial loading dose of 400 ng/kg TCDD prior to mating, followed by weekly maintenance doses of 80 ng/kg during mating, pregnancy, and the lactation period. Maternal exposure to TCDD had no significant effects on fetus/pup (F1) mortality, litter size, or sex ratio on gestation day (GD) 20 or postnatal day (PND) 2. The TCDD concentration in maternal livers and adipose tissue on GD20 was 1.21 and 1.81 ng/kg, respectively, and decreased at weaning to 0.72 in the liver and 0.84 in the adipose tissue. In contrast, the TCDD concentration in pup livers was 1.32 ng/kg on PND2 and increased to 1.80 ng/kg at weaning. Ventral prostate weight of male offspring was significantly decreased by TCDD exposure on PND28 and 120 compared with that of controls. Weight of the testes, cauda epididymides, and seminal vesicle, and sperm number in the cauda epididymis were not changed by TCDD exposure at PND120. TCDD- or vehicle-exposed male offspring were mated with unexposed females. The sex ratio (percentage of male pups) of F2 offspring was significantly reduced in the TCDD-exposed group compared with controls. These results suggest that in utero and lactational TCDD exposures affect the development of male gonads in offspring (F1), leading to changes in the sex ratio of the subsequent generation (F2).     

Effects of amaranth on F1 generation mice.

The color additive, amaranth, was given in the diet to provide dietary levels of 0 (control), 0.03, 0.09 and 0.27%, from 5 weeks of age in F₀ generation mice to 9 weeks of age in F₁ generation mice, and some reproductive, developmental and behavioral parameters were measured. There was no effect on the parameters of litters, litter size, pup weight and litter weight. The body weight of pups during the lactation period in the treatment groups increased less significantly, and the survival index at postnatal day (PND) 21 of the amaranth 0.27% group was reduced. Developmental parameters, direction of swimming on PND 4 in male pups and olfactory orientation in each sex were significantly reduced in the treatment groups. The dose levels of amaranth in this study influenced some reproductive, developmental and behavioral parameters in mice.     

Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice.

To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5-15 and 26-36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.     

Neurobehavioral and immunological effects of prenatal cocaine exposure in rat

Time-pregnant Sprague-Dawley rats were injected subcutaneously with 20 mg/kg of cocaine HCl or 0.9% saline daily from gestation days 15 through 21. Maternal plasma levels of approximately 720 ng/ml of cocaine did not alter maternal weight gain during treatment, duration of pregnancy, any of the litter variables or several indices of maternal behavior. Offsprings' body weight from birth to 30 days of age and physical maturation were not generally affected by prenatal cocaine exposure. While the development of surface righting, cliff avoidance, and the startle response was accelerated in cocaine-exposed offspring, acquisition of a preference for a social odor was unaltered. Prenatal cocaine also attenuated the locomotor response of the offspring to d-amphetamine and cocaine at PND 15; at PND 30 both of these catecholaminergic agonists increased activity in prenatal saline and prenatal cocaine offspring. However, the difference in plasma levels of cocaine at PND 30 suggests a possible down-regulation of adrenergic receptors following prenatal cocaine exposure. Decreased thymus/body weight ratios and splenomegaly were observed in prenatal cocaine animals at 55 days of age. Although complete neutralization of herpes simplex virus-type 1 was not observed, sera from prenatal cocaine offspring showed an increased rate of appearance of cytopathic effect, while sera from animals given cocaine postnatally showed a reduction in the rate at which viral infectivity was expressed in culture. These results indicate that prenatal cocaine exposure can alter neurobehavioral ontogeny and humoral immune responsitivity in the offspring.     

Effects of perinatal exposure to bisphenol A on the behavior of offspring in F344 rats

The objective of this investigation is to evaluate whether perinatal maternal exposure to bisphenol A (BPA) at 4, 40, and 400 mg/kg per day affects the behavior of offspring in F344 rats. Perinatal BPA exposure inhibited the body weight increases of male and female offspring in a dose-dependent manner, which continued after weaning. Spontaneous activity analyses revealed that BPA elongated immobile time during the dark phase in female offspring. At 4 weeks of age, male offspring exposed to BPA at 40 and 400 mg/kg per day performed avoidance responses significantly higher in the shuttlebox avoidance test. At 8 weeks of age, however, male offspring only at 4 mg/kg per day showed significantly lower responses. In the open-field behavior test at 8 weeks of age, male offspring exposed to BPA only at 4 mg/kg per day showed a higher percent of grooming than the control male offspring. In conclusion, perinatal exposure to BPA caused the behavioral alterations in the offspring.     

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats disrupts brain sexual differentiation

The effects of in utero and lactational exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on brain sexual differentiation were investigated. TCDD was orally administered to pregnant Holtzman rats on gestation day (GD) 15, and the activity of brain aromatase, a key enzyme for sexual differentiation, was measured in offspring on postnatal day (PND) 2. Changes in sexual dimorphisms of saccharin preference and the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) were examined in adult offspring. In controls, litter means of brain aromatase activity were higher in males than in females. In utero exposure to 200 ng/kg TCDD significantly decreased the sex ratio of aromatase activity (male/female) on PND 2. Offspring were weaned on PND28 and the saccharin test was started on PND84. In controls, saccharin (0.25%) intake (g/kg body weight) was significantly higher in female offspring than in males. In utero exposure to 200 ng/kg TCDD significantly increased saccharin intake in male offspring compared with control males, whereas 800 ng/kg TCDD had no effect. Neither dose of TCDD influenced saccharin intake of female offspring. In controls, SDN-POA volume was significantly greater in males than in females at 14 weeks of age. Exposure to 200 ng/kg TCDD significantly decreased SDN-POA volume in males, whereas 800 ng/kg TCDD had no effect. Neither doses of TCDD influenced the SDN-POA volume in female offspring. These results suggest that in utero and lactational TCDD exposure dose-dependently induces demasculinization in male offspring by inhibiting brain aromatase activity in the hypothalamus-preoptic area during central nervous system development.     

Effects of prenatal rubratoxin-B exposure on behaviors of mouse offspring.

The effects of prenatal rubratoxin-B (RB) exposure on 8 behavioral parameters in JCL:ICR mice were assessed. Pregnant mice were injected intraperitoneally with 0.1 or 0.2 mg/kg/day of RB dissolved in propylene glycol water solution on days 7-9 (Group A) or 10-12 (Group B) of gestation. Controls received the vehicle similarly on days 7-12 of gestation. Before weaning, the offspring of both sexes were examined to test their the surface righting reflex (5 days of age), cliff avoidance response (6 days), negative geotaxis response (7 days), and swimming development (8, 10, and 12 days). After weaning, male animals were examined using the rotarod test (6 weeks of age), the open-field test (7 weeks), the shuttle-box-avoidance-learning test (9 weeks), and the water E-maze test (10 weeks). The preweanling offspring in the 0.2 mg/kg-B group showed significantly lower success rates and longer response times than controls in the cliff-avoidance response. In swimming development, the offspring in the 0.2 mg/kg B group had significantly lower scores than controls for swimming angle at 10 and 12 days of age. The avoidance learning of the mice in all RB-exposed A and B groups was significantly poorer than that of controls. These results indicate that prenatal exposure to RB produced a delay of early response development and impaired learning ability in the offspring of mice exposed to RB during middle pregnancy.     

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.     

Age- and gender-dependent impairments of neurobehaviors in mice whose mothers were exposed to lipopolysaccharide during pregnancy

Lipopolysaccharide (LPS)-induced intrauterine infection has been associated with neurodevelopmental injury in rodents. The purpose of the present study was to analyze the dynamic changes of neurobehaviors in mice whose mothers were exposed to LPS during pregnancy. The pregnant mice were intraperitoneally (i.p.) injected with LPS (8 μg/kg) daily from gestational day (gd) 8 to gd 15. A battery of neurobehavioral tasks was performed in mice at postnatal day (PND) 70, 200, 400 and 600. Results showed that the spatial learning and memory ability, determined by radial six-arm water maze (RAWM), were obviously impaired in two hundred-day-old female mice and four hundred-day-old male mice whose mothers were exposed to LPS during pregnancy. Open field test showed that the number of squares crossed and peripheral time, a marker of anxiety and exploration activity, were markedly increased in two hundred-day-old female mice following prenatal LPS exposure. In addition, prenatal LPS exposure significantly shortened the latency to the first grid crossing in six hundred-day-old female offspring. Moreover, sensorimotor impairment in the beam walking was observed in two hundred-day-old female mice whose mothers were exposed to LPS during pregnancy. Species-typical behavior examination showed that prenatal LPS exposure markedly increased weight burrowed in seventy-day-old male offspring and six hundred-day-old female offspring. Correspondingly, prenatal LPS exposure significantly reduced weight hoarded in two hundred-day-old female offspring. Taken together, these results suggest that prenatal LPS exposure induces neurobehavioral impairments at adulthood in an age- and gender-dependent manner.     

The effect of lentinan on fertility and general reproductive performance of the rat

Lentinan, a polysaccharide [(1 → 3)-β-d-glucan], at 0.01, 0.10 or 1.0 mg/kg/day, was administered i.v. once daily to male rats for 9 weeks and to females for 2 weeks before mating. Some animals continued to be treated until they were killed during gestation: others were killed on day 21 post partum. Selected animals of the F1 generation were retained without further treatment, to provide F2 offspring. Reactions to treatment were generally dose-related and included bruising and cutaneous lesions of the tail and swelling and discolouration of the pinnae. In males given 1.0 mg/kg/day there was clear evidence of gonadal damage and impairment of reproductive capacity; this effect was less marked at 0.1 mg/kg/day and much reduced at 0.01 mg/kg/day. However, the reproductive performance of the selected F1 pups did not appear to have been affected by the treatment of the F0 parents at any dosage. In animals of both sexes there was a dose-related enlargement of the spleen, with evidence of macrophage infiltration.     

The effect of preconceptional exposure of F0 male mice to di(2-ethylhexyl)phthalate on the induction of reproductive toxicity in F2 generation

The aim of the study was the estimation of the effects of 8 weeks exposure mature and pubescent male mice to DEHP on the prenatal development of the offspring F2 generation.

The F1 offspring, of males exposed for whole cycle of spermatogenesis to DEHP (2000?mg/kg bw or 8000?mg/kg bw) and unexposed females, at 8–9?weeks of age were caged males with females from the same group, but from different litter.

Eight weeks preconceptional exposure of mature F0 males to 2000?mg/kg bw DEHP induced the significantly higher number of dead fetuses in the F2 offspring; however, the effect on the sperm count and quality of F1 males was not seen. Contrary, after such exposure of pubescent males not significantly decrease in the number of live implants was noted.

Results showed that the subchronical, preconceptional exposure of F0 males to DEHP did not influence strongly on the F2 generation of the offspring. Our study did not confirm higher sensitivity germ cells of pubescent males to harmful effects induced by DEHP. The developmental effect was present as the enhanced number of dead implants of F2 generation after exposure of mature F0 males and slight reduction in the number of live fetuses following the exposure of immature males. It may confirm ability to male mediated developmental toxicity.     

Reproductive effects of endosulfan on male offspring of rats exposed during pregnancy and lactation.

1. The reproductive effects of endosulfan on the male offspring of rats were examined. Dams were treated orally with 0, 1.5 or 3.0 mg endosulfan/kg from day 15 of pregnancy to postnatal day (PND) 21 of lactation. The male offspring rats were investigated at PND 65 or 140, corresponding to the pubertal and adulthood stage of development. 2. The dose of 3.0 mg endosulfan/kg induced a decrease in maternal body weight during pregnancy, but litter size and mean birth weight were not affected. Similarly, the age at testis descent and preputial separation was not affected on the male offspring. 3. The daily sperm production (x10(6)) was permanently decreased in the highest dose group when investigated at puberty and at adulthood. At the lowest dose, however, the daily sperm production was significantly reduced only at puberty. 4. Histologically, the percentage of seminiferous tubules showing complete spermatogenesis was significantly decreased at puberty. This finding may explain the decrease in daily sperm production observed in the endosulfan-exposed male rats. 5. The results of this study show that low doses of endosulfan have no apparent effect on developmental landmarks or on the weight of reproductive and accessory sex organ. Daily sperm production was the most susceptible endpoint in the male offspring exposed to endosulfan during pregnancy and lactation. To further understand the reproductive effects of endosulfan on male rat offspring, additional reproductive and toxicokinetic studies should be carried out to determine the extent of endosulfan exposure in male rat offspring in utero and during lactation.     

GENETIC FACTORS REGULATE THE RISE IN BLOOD PRESSURE IN F2 GENERATION CROSSED BETWEEN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR-KYOTO RATS

1. There was no significant difference between the systolic blood pressure (SBP) of offspring derived from SHRSP mother and WKY father and the SBP of offspring derived from WKY mother and SHRSP father at the developing stage (5-13 weeks of age). 2. The degree of genetic determinations of SBP in stroke-prone spontaneously hypertensive rat (SHRSP) at 5, 7, 10 and 13 weeks of age, determined by genetic crosses between SHRSP and WKY, was 73.9, 70.8, 50.2 and 55.3% respectively. 3. Significant correlations between SBP at 5 and 7 weeks, 7 and 10 weeks, 10 and 13 weeks, also at 5 and 13 weeks of age in F2 generation crossed between SHRSP and WKY were observed. SBP falling at or above the 80th percentile group in F2 generation at 5 weeks of age were constantly higher than SBP falling at or below the 20th percentile group from 7 weeks of age onwards. 4. These results indicate that there exists 'tracking phenomenon of SBP in SHRSP' and that genetic factors regulate the rise in SBP. Tracking of SBP in F2 generation gives us new methodological insight into hypertensive mechanism in SHR.