• Toxicological Research
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• v.13 no.1_2
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• pp.175-182
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• 1997

LBD-001, a recombinant human interferon $\gamma$ produced by genetically engineered yeast as a host system, was intravenously administered to pregnant female rats (Sprague-Dawley) from day 17 of gestation to day 21 of lactation at dose levels.of $0.35 \times 10^6$, $0.69 \times 10^6$, and $1.38 \times 10^6$ I.U./kg/day. In vasopressin-treated group, vasopressin (5 I.U./kg/day) was intravenously injected only for 5 days of perinatal period. (1) No signicant changes by the treatment of LBD-001 were observed in the body weights, food and water consumption, feeding and nurshing behaviors, and the weights of main organs of mother rats. In vasopressin-treated group, no significant changes were observed except the decrease in the food consumption on day 18 of gestation and one case of abnormal offspring with bleeding spots on the skin. (2) No significant changes in the body weights, survival rates, locomotor activity, emotional development. and the motor coordination of offsprings (F1) by the treatment of LBD-001 were observed except the fact that increase of ambulation in the female offsprings of LBD-001 ($0.69 \times 10^6$ or $1.38 \times 10^6$ I.U./kg/day)-treated groups and the increase of rearing in the males of LBD-($1.38 \times 10^6$ I.U./kg/day)-treated group, and the increase of the weight of liver and ovaries in the female offsprings in the LBD-001 ($1.38 \times 10^6$ I.U./kg/day)-treated group were observed. Altogether, the results show that LBD-001 at the dose of $1.38 \times 10^6$ I.U./kg/day or less does not significantly affect the mother rats and their offsprings (F1) except the minor influences when treated during the perinatal and postnatal period.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.23 no.3
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• pp.273-286
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• 2013

Objectives: The present study was conducted in order to investigate the reproductive toxicity in rats exposed to 1,4-dichlorobutane. Methods: The test chemical was administered orally at 0, 8.3, 50 and 300 mg/kg/day. Males were administered daily for 10 weeks prior to the mating period. Females were administered from between two weeks before mating to the 21stday of lactation. Results: In both sexes, a decrease in body weight and an increase in the weights of the liver and kidneys were observed. In males, discoloration of the liver, hepatocyte hypertrophy and mineralization in the kidneys were observed. In females, animal deaths, dystocia and pup deaths due to maternal dysfunction were observed. In F1 animals of both sexes, a decrease in body weight was observed at 300 mg/kg/day. An increase in the weights of the liver in both sexes, mineralization in the kidneys of males, animal deaths, hepatocyte hypertrophy and pup deaths due to maternal dysfunction were observed at 50 mg/kg/day. Mineralization in the kidneys of males was observed at 8.3 mg/kg/day. Therefore, the no-observed-adverse-effect levels (NOAELs) of 1,4- dichlorobutane were considered to be under 8.3 mg/kg/day for males, 8.3 mg/kg/day for females, more than 300 mg/kg/day for fertility in both sexes, 8.3 mg/kg/day for maternal functions and 50 mg/kg/day for F1 offspring. The absolute toxic dose was believed to be 8.3 mg/kg/day for males, 50 mg/kg/day for females, 50 mg/kg/day for maternal functions and 300 mg/kg/day for F1 offspring. However NOAEL for fertility could not be determined since there were no treatment-related changes. Conclusions: Under the present experimental conditions, 1,4-dichlorobutane is a Category 1B Reproductive Toxicant (presumed human reproductive or developmental toxicant).

• Toxicological Research
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• v.24 no.1
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• pp.51-58
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• 2008

The present study was designed to explore the immunotoxic effects of orally administered aluminum (AI) on pregnant rats (n = 60) and their growing fetuses and consequently on the animal wealth. The animals were randomly allocated into three equal groups of 20 rats each. The first group has no treatment and kept as a control (G1). The second and third groups of pregnant rats were treated orally with aluminum chloride at 345 mg/Kg b.wt. The second group (G2) received the tested compound from the $6^{th}$ day of gestation to the end of weaning, whereas the third group (G3) received the tested compound from the $15^{th}$h day of gestation to the end of weaning. Control and treated animals (dams and offspring) were immunized ip with (0.5 ml) 20% sheep red blood cell (SRBC) suspension seven days before the end of experiments. At the end of exposure, ten dams and ten offspring from each group were used for assessment of cell-mediated immunity and a similar number of animals were sacrificed for evaluating the humoral immune response and serum protein profile. Aluminum chloride exposure of dams ($G_2&G_3$) caused significant suppression of both cell mediated and humoral immune responses in the obtained offsprings compared to the control group ($G_1$) without any significant effect on the immune responses of these dams. Moreover, the serum total globulins, albumin/ globulin (A/G) ratio and gamma globulin fraction were significantly decreased in the treated dam's offsprings compared to the corresponding controls while the serum total protein and all serum protein fractions showed non significant difference between the control and treated dams and between the two treated dam groups themselves. There were no histopathological changes observed in thymus, spleen and liver of the control and treated dams. Thymus of treated dam's offsprings (G2) showed lymphoid depletion in both cortex and medulla. Their spleens showed lymphoid depletion in the white pulps and congestion with hemosiderosis in the red pulps. Liver of treated dam's offsprings showed dilation and congestion of its central vein with degenerative changes in the hepatocytes. These histopathological changes were more severe in G2 than in G3 offsprings. It can be concluded that gestational and/ or lactation exposure of pregnant dams to AI chloride caused suppression of both cellular and humoral immune responses of their offsprings.

• Journal of Life Science
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• v.25 no.7
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• pp.765-772
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• 2015

The aim of this study was to determine the effect of decursin (D) and decursinol angelate (DA) against bisphenol A (BPA) toxicity in a rat two-generation study. Adult rats were divided into the following three groups: (1) control, (2) BPA, and (3) BPA+D/DA. The D and DA treatment of F0 parents increased the terminal body weight and relative adult organ weights (testes, kidneys, spleen, and liver) when compared with the BPA group. A significant decrease in sperm count was found in the BPA+D/DA (7.69%) and BPA (64.70%, p<0.01) groups, when compared with the sperm count in the control group. No offspring were obtained in the F1 generation of the BPA (50 mg/kg/day) group, but the addition of D/DA in the BPA+D/DA group significantly restored fertility (55.78%) and gestation indices (98.87%) in the F1 generation. No significant differences were found in the fertility index between the control (75.02%) and the BPA+D/DA (78.11%) groups in the two-generation study, when compared with the one-generation study. The viability ratio during lactation in the D/DA group was also similar to that of the control group. These data indicate that D/DA (50 mg/kg/day) administered over two generations causes significant positive changes in reproductive or developmental parameters.

• Korean Journal of Environmental Biology
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• v.21 no.2
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• pp.208-215
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• 2003

Bisphenol A (4,4'-isopropylidenediphenol, $C^{15}H_{16}O_{2}$) is the monomer used in the manufacture of polycarbonate. Polycarbonate, in turn, is used in a wide array of plastic products, with new applications continuously being developed. Also it has been used to produce epoxy resins and polycarbonate plastics for food container. This study was carried out to investigate the effects of bisphenol A on lactation period to dams and F1. Sprague-Dawley females were mated with on 2 : 1 ratio basis. Various doses of bisphenol A (0, 2, 20, 200, and 2,000 ${\mu}g kg^{-1}$) were daily administered to females for 21 days after parturition. Dams and offsprings were sacrificed at the time of weaning. The results were as fellows, 2000 ${\mu}g \; kg^{-1}$ / of bisphenol A decreased the dams' body weight at post-partum 18 days and also 200 and 2,000 ${\mu}g \;kg^{-1}$ of bisphenol A decreased the body weight of neonates at the days of post-partum 21 days. Bisphenol A increased the relative weights of liver and spleen in male offsprings, depending on the doses. But female offsprings showed high relative organ weights of ovaries, and low relative organ weights of uterine in a some dose-response manners. High dose of bisphenol A induced low viability of neonates exposed during lactation period. The dams treated with bisphenol A showed prematured estrous stage. Bisphenol A was recovered about 21.2% average in serum of dams, and also in offsprings'. The results indicate that the bisphenol A induces estrous cycle during lactation period in dams, also reaches to the offspring through breast milk. Thus bisphenol A exopsed to dams and neonates via lactation induces some estrogenic and tonic effects.

• Proceedings of the Korean Environmental Health Society Conference
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• 2003.06a
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• pp.171-173
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• 2003

Bisphenol A (4,4'-isopropylidenediphenol, C$\_$15/H$\_$16/O$_2$) is the monomer used in the manufacture of polycarbonate. Polycarbonate, in turn, is used in a wide array of plastic products, with new applications continuously being developed. Also it has been used to produce epoxy resins and polycarbonate plastics for food container. This study was carried out to investigate the effects of bisphenol A on lactation period to dams and F1, Sprague-Dawley females were mated with on 2:1 ratio basis. Various doses of bisphenol A (0, 2, 20, 200, and 2,000 $\mu\textrm{g}$/kg) were daily administered to females for 21 days after parturition. Dams and offsprings were sacrificed at the time of weaning. The results were as follows, 2000 $\mu\textrm{g}$/kg of bisphenol A decreased the dams' body weight at post-partum 18 days and also 200 and 2000 $\mu\textrm{g}$/kg of bisphenol A decreased the body weight of neonates at the days of post-partum 21 days. Bisphenol A increased the relative weights of liver and spleen in male offsprings, depending on the doses. But female offsprings showed high relative organ weights of ovaries, and low relative organ weights of uterine in a some dose-response manners. High dose of bisphenol A induced low viability of neonates exposed during lactation period. The dams treated with bisphenol A showed prematured estrous stage. Bisphenol A was recovered about 21.2% average in serum of dams, and also in offsprings'. The results indicate that the bisphenol A induces estrous cycle during lactation period in dams, also reaches to the of offspring through breast milk. Thus bisphenol A exopsed to dams and neonates via lactation induces some estrogenic and toxic effects.

• Journal of Nutrition and Health
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• v.19 no.4
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• pp.246-254
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• 1986

Weanling female Sprague Dawley rats were fed d diets containing 22mg pyridoxine. BCI/kg diet (control diet) and l.2mg pyridoxine. BCI/kg diet (deficient diet). One control group and one defi­c dent group were fed their diet throughout growth, g gestation and lactation. After the pups were born and weaned, the deficient group was divided into two groups. One switched to control diet(supple­I mented group) and the other continued the same d deficient diet( deficient group) until 10 week -old. The liver mitochondrial and cytosolic asparate a aminotransferase activity and pyridoxal phosphate content were determined in offspring rats. The aspartate aminotransferase activities in both liver mito$\phi$ondrial and cytosolic fractions of den­d cient group were significantly lower than those of controls, but there were no significant differences between two groups after addition of 1O^{-4}M pyri­d do뼈I phosphate to the medium. By pyridoxine s supplementation after weaning, the reduced aspar­a tate aminotnmsferase activities were only partialy I restored to control levels. The pyridoxal phospha­t te content of deficient group in Iiver mitochondr­ial and cytosoIic fractions were alo significantly different from those of controls, but readily restored by dietary supplementation. These results suggest that there is a quantitative and a qualitative changes of aspartate amino trans­f ferase and pyridoxal phosphate in liver mitochon­d drial and cytosolic fraction by long-term pyrido­x xine deficiency and these reductions can partially recovered by dietary pyridoxine supplementation after weaning.