Ninety days of repeated gavage administration of Rhodiola imbricata extract in rats

Rhodiola imbricata is a high‐altitude plant, possesses adaptogenic, immunomodulatory, anti‐oxidant and cytoprotective activity, and is widely used in traditional medicine. The present study was designed to ascertain the safety of aqueous extract of R. imbricata root when administered by gavage to rats for 90 days. Four groups of animals, each consisting of 15 males and 15 females, were administered 0, 100, 250 or 500 mg kg^?1 extract, in a single dose per day. The experimental rats when administered 100 mg kg^?1 of extract did not show any significant change in their body weight gain, organ/body weight ratio, or histological, hematological and biochemical variables studied. However, at higher doses of 250 and 500 mg kg^?1 extract, an increase in the body weight of rats of both the sexes was apparent without any change in their organ/body weight ratio. Furthermore, a noteworthy increase in plasma glucose and protein levels was recorded at both the higher doses, which were restored to normal after a 2‐week withdrawal of treatment. Based on the findings of this study, the no observed effect level was 100 mg kg^?1 body weight per day of aqueous root extract of R. imbricata in rats administered subchronically. Copyright © 2011 John Wiley & Sons, Ltd.     

Effects of Jatropha oil on rats following 28‐day oral treatment

Jatropha oil is an emerging feedstock for the production of biodiesels. The increasing use of this nonedible, toxic oil will result in higher potential for accidental exposures. A repeated‐dose 28‐day oral toxicity study was conducted to provide data for risk assessment. Jatropha oil diluted in corn oil was administered by gavage to male and female rats at 0.5, 5, 50 and 500 mg kg^?1 body weight per day for 28 consecutive days. Control rats were administered corn oil only. The growth rates and consumption of food and water were monitored. At necropsy, organs were weighed and hematological parameters assessed. Serum clinical chemistry and C‐reactive protein were measured and histological examinations of organs and tissues were performed. Markedly depressed growth rate was observed in males and females receiving Jatropha oil at 500 mg kg^?1 per day. Decreased white blood cell and lymphocyte counts were detected in females at 50 and 500 mg kg^?1 per day and in males at 500 mg kg^?1 per day. These changes were correlated to mild and reversible histological changes in male and female spleens. In the liver, a mild increase in portal hepatocytes cytoplasm density was observed in males and females, while periportal vacuolation was observed exclusively in females. Mild acinar proliferation was observed in the female mammary glands at all dose levels. It is concluded that Jatropha oil produces adverse effects on female rats starting at 50 mg kg^?1 per day with decreased white blood cell and lymphocyte counts and at 500 mg kg^?1 per day in both genders in term of depressed growth rates. Copyright © 2011 John Wiley & Sons, Ltd.     

Subchronic hepatotoxicity evaluation of bromobenzene in Fischer 344 rats

Male Fischer 344 (F344) rats were exposed to bromobenzene (BB) for 5 days and 2, 4 and 13 weeks. BB was administered by gavage (corn oil vehicle) at doses of 0, 25, 100, 200, 300 and 400 mg kg^?1 per day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood BB, gross pathology and liver histopathology. There were no BB exposure‐related clinical signs of toxicity. Mean body weight decreased by 5–10% compared with control in the 400 mg kg^?1 per day group. Liver weight increases were dose‐ and exposure time‐related and statistically significant at ≥25 mg kg^?1 per day. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were related to dose and exposure time. At early time points (5 days and 2 weeks), centrilobular inflammation, including granulomatous areas, and necrotic and anisokaryocytic hepatocytes were observed in rats of the two highest BB dose groups. Blood BB concentrations increased linearly with dose and at 13 weeks ranged from 8 to 136 µg ml^?1 (25–400 mg kg^?1 per day). In conclusion, rats administered BB doses up to 400 mg kg^?1 per day for up to 13 weeks had mild liver effects. A NOAEL of 200 mg kg^?1 per day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥ 400 mg kg^?1 per day. Copyright © 2012 John Wiley & Sons, Ltd.     

Shift of oxidants and antioxidants levels in rats as a reaction to exposure to sulfur mustard

Antixodants as well as oxidants levels were investigated in plasma of rats exposed to sulfur mustard in doses of 0 (control), 5, 20 and 80 mg kg^?1 body weight. Cyclic voltammetry performed on screen‐printed strips with platinum working electrode used as a tool for assaying oxidant and antioxidant levels. We found significant shifts in both examined analytes. A dose of sulfur mustard of 5 mg kg^?1 body weight caused only a small change in oxidant and antioxidant levels when compared with the control group. A dose of 20 mg kg^?1 body weight provided a significant increase in antioxidants as well oxidants; however, the ratio of both was similar to that in the control group. The most surprising facts were found when the highest dose of 80 mg kg^?1 body weight of sulfur mustard was applied. While antioxidants were significantly increased, oxidants were decreased on an extensive scale. Copyright © 2009 John Wiley & Sons, Ltd.     

Oral Toxicity Study of 2-Pentenenitrile in Rats with Reproductive Toxicity Screening Test

A combined repeated-dose toxicity study with reproduction was conducted with 2‐pentenenitrile (2-PN). Rats (10/sex per dose level) were dosed with 2-PN once daily by gavage at dose levels of either 0, 1, 3, or 10 mg kg^?1 day^?1 for 28 days, prior to and during cohabitation, and through day 3 of lactation. General clinical observations were recorded daily; body weights were recorded weekly. A neurobehavioral evaluation consisting of a functional observational battery and motor activity was conducted in all parental rats (10/sex per group). Clinical pathology parameters (hematology, clinical chemistry, coagulation) were measured in parental rats. Pup weights and clinical signs were recorded at birth and on lactation day 4. Parental rats were given a gross pathological examination, organ weights were obtained, and histological examination was conducted for the control and 10 mg kg^?1 day^?1 groups. No effects were seen with regard to mortality, clinical signs, functional observational battery and motor activity, hematology, or organ weights. Females receiving 10 mg/kg and males from all dose groups showed lower body weight gains and feed efficiency. Increased albumin concentrations were seen in both sexes given 10 mg/kg. Females in the 10 mg/kg group showed degeneration of the olfactory mucosa. No effects on the numbers of pups born, number surviving to lactation day 4, pup weight, and no gross anatomical development changes were observed. Under the conditions of this study, the no-observed-effect level (NOEL) for systemic toxicity in rats was 3 mg kg^?1 day^?1, based on degeneration of olfactory mucosa in females at 10 mg kg^?1 day^?1. The NOEL for reproductive and neurobehavioral toxicity in rats and for toxicity to offspring was 10 mg kg^?1 day^?1, the highest dose level tested.     

Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure

The increasing application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse effects to human and the environment. However, the knowledge on the systemic toxicity of AgNPs in mammalian systems is still limited. The present study investigated the toxicity of PVP‐coated AgNPs in rats treated with repeated oral administration, and compared that with equivalent dose of AgNO₃. Specifically, one hundred male and female rats were orally administrated with particulate or ionic forms of silver (Ag) separately at doses of 0.5 and 1 mg kg^?1 body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO₃ up to 1 mg kg^?1 body weight, with respect to the body weight, organ weight, food intake, and histopathological examination. Ag distribution pattern in organs of rats treated with AgNPs was similar to that of AgNO₃ treated rats, showing liver and kidneys are the main target organs followed by testis and spleen. The total Ag contents in organs were significantly lower in the AgNPs treated rats than those in the AgNO₃ treated rats. However, the comparisons between AgNPs and AgNO₃ treatments further indicated more potent of AgNPs in biochemical and hematological parameters in rats, including red blood cell count (RBC), platelet count (PLT), white blood cell count (WBC) and aspartate transaminase (AST). Results of this study suggested that particulate Ag at least partially contributed to the observed toxicity of AgNPs, and both ionic and particulate Ag should be taken into consideration in toxicological evaluation of AgNPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 609–618, 2017.     

Evaluation of the effects of deltamethrin on the fetal rat testis

Pregnant Sprague–Dawley rats were administered deltamethrin, at doses 0.1, 1, 5 or 10 mg kg^?1 day^?1, or di‐n‐hexyl phthalate (DnHP) (250 mg kg^?1 day^?1), by gavage, from gestational day 13 to 19. Maternal toxicity was observed at 10 mg kg^?1 day^?1, as evidenced by transient clinical signs of neurotoxicity and reductions in body weight, body weight gain and corrected weight gain. Deltamethrin had no statistically significant effect on the incidence of post‐implantation loss, fetal weight or anogenital distance in the male fetuses. Unlike DnHP, deltamethrin induced no changes in the expression of several genes involved in cholesterol transport or in the steroid synthesis pathway in the testes of gestational day 19.5 male fetuses (SRB1, StAR, P450scc, 3βHSD, P450 17 A1, 17βHSD). Fetal testicular levels of P450scc and P450 17 A1 protein were also unaffected by deltamethrin. No statistically significant differences were observed in the ex vivo fetal testicular production of testosterone and androstenedione after deltamethrin exposure, whereas DnHP markedly reduced these parameters. The deltamethrin metabolite, 3‐phenoxybenzoic acid, was detected in amniotic fluid. In summary, our results demonstrate that in utero exposure to deltamethrin during the period of sexual differentiation had no significant effect on the testosterone synthesis pathway in the male rat fetus up to a maternal toxic dose. Copyright © 2016 John Wiley & Sons, Ltd.     

High doses of 2,2′‐dithienyl diselenide cause systemic toxicity in rats: an in vitro and in vivo study

Organoselenium compounds have important pharmacological properties. However, these compounds can cause toxicity, typically related to oxidation of endogenous thiols. The aim of this study was to investigate whether 2,2′‐dithienyl diselenide (DTDS) has potential toxicity in vitro and in vivo. Therefore, sulfhydryl‐containing enzyme activities, δ‐aminolevulinic acid dehydratase (δ‐ALA‐D) and Na⁺–K⁺‐ATPase were used to predict DTDS toxicity in rat brain homogenate in vitro. In in vivo experiments, a DTDS administration (50 or 100 mg kg^?1, p.o.) to rats was performed and toxicological parameters were determined. DTDS inhibited δ‐ALA‐D (IC₅₀ 2 µm ) and Na⁺–K⁺‐ATPase (IC₅₀ 17 µm ) activities in vitro. The inhibitory effect of DTDS on δ‐ALA‐D and Na⁺–K⁺‐ATPase activities was restored by dithiothreitol. DTDS (5–25 µm ) elicited a thiol oxidase‐like activity. In vivo, DTDS (50 and 100 mg kg^?1) caused systemic toxicity, evidenced by a decrease in water and food intakes and body weight gain, as well as the death of rats. DTDS at the dose of 100 mg kg^?1 increased plasma alanine and aspartate aminotransferase activities and decreased urea levels. At 50 and 100 mg kg^?1, it increased lipid peroxidation levels. At the highest dose, DTDS inhibited δ‐ALA‐D activity. By contrast, Na⁺–K⁺‐ATPase activity and antioxidant defense were not altered in the brains of rats exposed to DTDS. In conclusion, interaction with the cisteinyl residues seems to mediate the inhibitory effect of DTDS on sulfhydryl‐containing enzymes in vitro. In addition, high oral doses of DTDS induce toxicity in rats. Copyright © 2011 John Wiley & Sons, Ltd.     

Developmental toxic potential of di‐n‐propyl phthalate administered orally to rats

The objective of this study was to evaluate the developmental toxic potential of di‐n‐propyl phthalate (DnPP) in rats. Pregnant Sprague–Dawley rats were given DnPP at doses of 0 (olive oil), 0.5, 1 and 1.5 g kg^?1 per day, by gavage, on gestation days 6–20. Benchmark doses were calculated for the effects of DnPP on fetal weight and anogenital distance of the male fetuses. Maternal body weight gain was significantly reduced at 1.5 g kg^?1 per day, over gestation days 6–9. DnPP‐treated dams also showed a statistically significant increase in liver weight and a mild but statistically significant peroxisomal enzyme induction at 1 or 1.5 g kg^?1 per day. Male and female fetal body weights were significantly reduced at 1.5 g kg^?1 per day. There was a statistically significant decrease in the anogenital distance of the male fetuses at 1 and 1.5 g kg^?1 per day, and three males (of 75) showed malpositioned testis at the high dose. The mean percentage of fetuses per litter with cervical and thoracic rudimentary ribs was significantly increased at 1 and 1.5 g kg^?1 per day. Delayed ossification was seen at 1 g kg^?1 per day (phalanges) and 1.5 g kg^?1 per day (hyoid, sternebrae, and phalanges). No treatment‐related effects on prenatal viability or on fetal external or visceral malformations or variations were observed at any dose. Thus, there was no evidence of teratogenicity up to the high dose of 1.5 g kg^?1 per day. The no‐observed‐adverse‐effect level (NOAEL) for developmental toxicity was 0.5 g kg^?1 per day. Copyright © 2010 JohnWiley & Sons, Ltd.     

Preclinical safety evaluation of low molecular weight heparin–deoxycholate conjugates as an oral anticoagulant

The preclinical safety of a newly developed oral anticoagulant, the low molecular weight heparin–deoxycholate conjugate (OH09208), was evaluated by a comprehensive evaluating program in compliance with standard guidelines. The single dose oral toxicity study in rats receiving 2000 and 5000 mg kg^?1 of OH09208 did not reveal any mortality, unusual body weight changes or necropsy findings. The results of the 4‐week oral toxicity study with a 4‐week recovery program in rats receiving OH09208 in doses of 100, 300 and 1000 mg kg^?1 day^?1 did not reveal any mortality, or indicate any unusual clinical signs, or show any toxicokinetic relationships to the administration of OH09208. Although the increase in liver enzymes in one male dog treated with 300 mg kg^?1 day^?1 and one female dog treated with 1000 mg kg^?1 day^?1 could not be excluded from the effect of the test substance, no other toxicologically significant changes were observed in the 4‐week oral toxicity study with a 4‐week recovery in beagle dogs. Thus, while the no‐observed‐adverse‐effect level value from the 4‐week study in both male and female rats was 1000 mg kg^?1 day^?1, those from the 4‐week study in male and female beagle dogs were 300 and 1000 mg kg^?1 day^?1, respectively. Furthermore, OH09208 did not induce anaphylactic reactions in guinea pigs, micronucleated bone marrow cells in male ICR mice, chromosomal aberration in Chinese hamster lung cell lines, bacterial reverse mutation, and any abnormalities in hERG current assay, mouse central nervous system and dog cardiovascular studies. Overall, there were no unexpected toxicities in this preclinical study that might have precluded the safe administration of OH09208 to humans. Copyright © 2015 John Wiley & Sons, Ltd.     

Evaluation of sub-chronic oral toxicity of Joloo: A traditional medicinal decoction

Context: Joloo is a Nigerian herbal decoction used for managing breast tumor, ulcer, pain, fever and general malaise in southwestern Nigeria.

Objective: The evaluation of the sub-chronic toxicity of Joloo, a Nigerian herbal decoction, is done by investigating its effects on biochemical, antioxidant, histopathologic and hematologic indices in normal albino rats.

Materials and methods: Albino rats of either sex weighing between 128 and 160?g were divided into 4 groups of 10 rats each. Three test groups were orally administered 400, 800 and 1600?mg kg^?1 body weight (b. wt.) doses of Joloo while control animals received distilled water over 28 days. Animal were weighed weekly and sacrificed after day 28. Organs were harvested, weighed and subjected to histopathologic assessment. Liver and blood samples were used for biochemical, antioxidant and hematological studies.

Results: Mortality and signs of toxicity were absent in animals treated with 400 and 800?mg kg^?1 doses of Joloo. At 1600?mg kg^?1 dose, 20% mortality occurred. Decreased body weight and red blood cells (P?<?0.05) observed at 1600?mg kg^?1 differed significantly from control animals. No significant changes in body and organ weights presented. Significant increases in biochemical analytes and histopathologic parameters were unobserved. Rather, Joloo increased leukopoiesis and exhibited antioxidant activities at all doses.

Discussion: Joloo proved safe at lower doses. The mortality at 1600?mg kg^?1 could be due to disturbances in the physiology of the animals. The significant reduction in erythropoiesis could indicate early signs of toxicity. However, the unremarkable increases in hepatic and antioxidant enzymes may suggest that Joloo modulated oxidative status in the animals.

Conclusion: Joloo seems safe at lower doses, but caution is advised at higher doses.     

Hyaline droplet accumulation in kidney of rats treated with hexachloro‐1:3‐butadiene: influence of age,dose and time‐course

The present research investigates the occurrence of hyaline droplet (HD) accumulation related to age, dose and time after treatment in male Wistar rats given a single i.p. injection of hexachloro‐1:3‐butadiene (HCBD). In the study on age, rats from 1 to 12 months of age were treated with 100 mg kg^?1 body weight (b.w.) HCBD dose. Rats treated at 2 months of age showed a greater accumulation of HD than the other age groups; HD accumulation was not observed in 1‐month‐old rats. In the dose–response study, the treatment with 25, 50 and 100 mg kg^?1 b.w. at 2 months of age caused HD accumulation in the proximal convoluted tubule at all doses, with the 100 mg kg^?1 b.w. group slightly more affected. Finally, in the time‐course study, rats treated with a 100 mg kg^?1 b.w. dose at 2 months of age and sacrificed at 6, 12, 24, 48, 72 and 96 h post‐dosing showed a time‐related HD accumulation in terms of incidence and severity, after 6 h, with a peak at 24 and 48 h and decreasing at 72 and 96 h. The present results show that HD accumulation is an early finding, and is unrelated to dose level and particularly evident in rats of 2 month of age. These findings in male rats treated with HCBD emphasize the importance of considering the age of rats at the start of a study. The more sensitive model was used in the detection of nephrotoxic effects of chemicals. Copyright © 2011 John Wiley & Sons, Ltd.     

Preliminary safety evaluation of a taurocholate‐conjugated low‐molecular‐weight heparin derivative (LHT7): a potent angiogenesis inhibitor

In our previous studies, taurocholic acid (TA)‐conjugated low‐molecular‐weight heparin derivative (LHT7) has been proven to be a potent anti‐angiogenic agent by demonstrated successful blockage capability of vascular endothelial growth factors (VEGF). Preliminary safety evaluations were conducted based on its mechanism of action and chemical behavior. For this purpose, acute toxicity study, and hematological and serological evaluations were carried out. Additionally, in order to evaluate mechanism‐related side effects, both blood pressure and the occurrence of proteinuria were measured using a treatment regime of multiple high doses of LHT7 in a biodistribution study. LD₅₀ values for LHT7 in female and male mice were 56.9 and 64.7 mg kg^–1 doses, respectively. There were no vital fluctuations in the serological and hematological parameters, except for the elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 100 and 200 mg kg^–1 doses of LHT7, representing vital changes in the liver function. Moreover, the results of mechanism‐related studies showed that blood pressure at 50 mg kg^–1 did not change but showed elevated levels of protein in urine. In the biodistribution study, a slight accumulation of LHT7 in the kidney and the liver were observed at the 50 mg kg^–1 repeated dose owing to the presence of bile acid. No fatal damage was observed in this study; most observations were related to the chemical composition or the mechanism of action of the material. Copyright © 2014 John Wiley & Sons, Ltd.     

Effects of melamine on pregnant dams and embryo‐fetal development in rats

There are worldwide concerns regarding the potential adverse effect of melamine. This study investigated the potential effects of melamine on pregnant dams and embryo‐fetal development in Sprague–Dawley rats following maternal exposure on gestational days (GD) 6–20. Melamine was administered to pregnant rats by gavage at doses of 0, 200, 400 and 800 mg kg^?1 per day (n = 8–10 for each group). All dams were subjected to a Caesarean section on GD 21 and their fetuses were examined for morphological abnormalities. With administration of melamine at 800 mg kg^?1 per day, maternal toxicity manifested as increased incidences of clinical signs and death, lower body weight gain and food intake, and increases in heart, adrenal gland and kidney weights. Histopathological examinations revealed an increase in incidences of congestion, tubular necrosis/degeneration, crystals, casts, inflammatory cells in tubules, tubular dilation and tubular hyaline droplets in the maternal kidneys, while fetal kidneys (one fetus/litter) did not show any histopathological changes. Developmental toxic effects included a decrease in fetal weight, an increase in the incidence of skeletal variations and a delay in fetal ossification. No treatment‐related maternal or developmental effects were observed at doses ≤400 mg kg^?1 per day. These results show that 15‐day repeated oral dosing of melamine is embryo‐/fetotoxic at a maternotoxic dose, but not teratogenic in rats. The no‐observed‐adverse‐effect level of melamine for pregnant dams and embryo‐fetal development is considered to be 400 mg kg^?1 per day. Copyright © 2011 John Wiley & Sons, Ltd.     

Evaluation of the Reproductive and Developmental Toxicity of a Fluoroalkylethanol Mixture

The objective of these studies was to evaluate the reproductive and developmental toxicity of a commercial fluoroalkylethanol mixture, which is an intermediate in the production of fluorotelomers. The test substance was administered daily by gavage to Sprague–Dawley rats as a suspension in 0.5% aqueous methylcellulose. In a one-generation reproductive toxicity study, rats (20 per sex per group) were given dosages of 0, 25, 100, or 250 mg kg^{? 1} day^{? 1} for a period of 74 days prior to cohabitation, and during mating, gestation, and lactation. Body weights, feed consumption, clinical signs, gross pathology, sperm parameters, estrous cyclicity, and reproductive performance were evaluated for the P₁ generation. The F₁ offspring were evaluated during the lactation period for growth and survival and given a gross pathology examination at weaning. A subset of the offspring were retained; body weights, feed consumption, clinical signs, and age at onset of vaginal opening and preputial separation were evaluated, and gross pathology was performed on postnatal day 60. In the developmental toxicity study, groups of time-mated Sprague–Dawley female rats were given the test substance as a suspension in 0.5% aqueous methylcellulose at daily dosages of 0, 50, 200, or 500 mg kg^{? 1} day^{? 1} by gavage on gestation days 6–20. During the in-life portion of the study, growth parameters and clinical observations were made. On gestation day 21, dams were euthanized, and the thoracic and abdominal viscera were examined. The uterine contents were removed and examined, and fetuses were evaluated for any alterations. In the reproduction study, litter size at birth, number of live pups per litter on day 0 and 4 of lactation, and pup weights during lactation were reduced in groups administered ≥ 100 mg kg^{? 1} day^{? 1}. No other reproductive parameters were affected. There were no adverse reproductive effects observed at 25 mg kg^{? 1} day^{? 1}. In the developmental toxicity study, reduced maternal body weight parameters, increased perineal fur staining, and increased fetal skeletal alterations were observed at 500 mg kg^{? 1} day^{? 1}. There was no maternal or developmental toxicity at 50 or 200 mg kg^{? 1} day^{? 1}. Under the conditions of the studies, the no-observed adverse effect levels for this mixture were 25 mg kg^{? 1} day^{? 1} for subchronic toxicity and reproductive parameters and 200 mg kg^{? 1} day^{? 1} for developmental toxicity end points. No functional reproductive or developmental effects were observed at dose levels that did not adversely affect adult animals.     

Juvenile rats do not exhibit elevated sensitivity to acrylamide toxicity after oral administration for 12 weeks

Acrylamide (AA), a neurotoxic, testicular toxic, genotoxic and carcinogenic chemical, has been reported to be formed in processed food, and sensitivity to AA intoxication in childhood is a concern. In the present study, to clarify the general toxicological profile of AA in juvenile rats, subchronic toxicity was evaluated in F344 rats administered AA in the drinking water at 0 (control), 10, 20 and 40 ppm, presented to the dams (three per group) immediately after the birth of their litters, through lactation (3 weeks), and directly to the offspring in their drinking water after weaning for a further 9 weeks (12 weeks total). Treatment with AA caused a decrease in body weights in 20 and 40 ppm F₁ females, compared with the controls. Average AA intake throughout the treatment period for the 10, 20 and 40 ppm groups after weaning was equivalent to 1.0, 2.1 and 4.4 mg kg^?1 body weight per day, respectively, in males and 1.2, 2.5 and 4.9 mg kg^?1 body weight per day, respectively, in females. No toxicologically significant organ weight changes were observed. AA‐induced histopathological changes were limited to focal degeneration and necrosis of the seminiferous epithelium in the testes and desquamated epithelium in the ducts of epididymides, noted only in 40 ppm males. Taken together with previous reports, juvenile rats are not necessarily more susceptible to AA‐induced toxicity as compared with young adults. Copyright © 2011 John Wiley & Sons, Ltd.     

Thirteen week toxicity study of dietary l‐tryptophan in rats with a recovery period of 5 weeks

Although l ‐tryptophan is nutritionally important and widely used in medical applications, toxicity data for its oral administration are limited. The purpose of this study was to evaluate the potential toxicity of an experimental diet containing added l ‐tryptophan at doses of 0 (basal diet), 1.25%, 2.5% and 5.0% when administered to Sprague–Dawley rats for 13 weeks. There were no toxicological changes in clinical signs, ophthalmology, urinalysis, hematology, necropsy, organ weight and histopathology between control rats and those fed additional l ‐tryptophan. Body weight gain and food consumption significantly decreased throughout the administration period in males in the 2.5% group and in both sexes in the 5.0% group. At the end of the dosing period, decreases in water intake in males in the 5.0% group and in serum glucose in females in the 5.0% group were observed. The changes described above were considered toxicologically significant; however, they were not observed after a 5 week recovery period, suggesting reversibility. Consequently, the no‐observed‐adverse‐effect level of l ‐tryptophan in the present study was 1.25% for males and 2.5% for females (mean intake of l ‐tryptophan: 779 mg kg^–1 body weight day^–1 [males] and 1765 mg kg^–1 body weight day^–1 [females]). As the basal diet used in this study contained 0.27% of proteinaceous l ‐tryptophan, the no‐observed‐adverse‐effect level of overall l ‐tryptophan was 1.52% for males and 2.77% for females (mean intake of overall l ‐tryptophan: 948 mg kg^–1 body weight day^–1 (males) and 1956 mg kg^–1 body weight day^–1 (females)). We conclude that l ‐tryptophan has a low toxicity profile in terms of human use.     

Acute toxicity and tissue distribution of CdSe/CdS‐MPA quantum dots after repeated intraperitoneal injection to mice

Quantum dots (QDs) are novel tools with multiple biological and medical applications because of their superior photoemission and photostability characteristics. However, leaching of toxic metals from QDs is of great concern. Therefore, for the successful application of QDs in bioscience, it is essential to understand their biological fate and toxicity. We investigated toxicological effects and tissue distribution of mercaptopropionic acid‐conjugated cadmium selenide/cadmium sulfide (CdSe/CdS‐MPA) QDs after repeated intraperitoneal injection into BALB/c mice. The mice were injected every 3 days with various doses of QDs (0, 5, 10 and 25 mg kg^?1). The subsequent effects of QDs on plasma levels of various biomarkers were evaluated at different time points (at 0, 1, 4, 7, 10, 13 and 15 days). Various tissue samples (spleen, liver, lung, kidneys, brain, heart and thymus) were collected for toxicity analysis, distribution testing, histopathological examination and inflammation assessment. No abnormal clinical signs or behaviors were recorded but the body weight of mice treated with 25 mg kg^?1 QDs was significantly decreased from day 7 compared with control mice. QDs were observed in the liver, spleen, lung and kidneys, but not in brain or heart. Significantly higher levels of lactate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase were found in the plasma, liver and spleen. Histopathological examination did not show any tissue toxicity but the levels of interleukin‐6, a pro‐inflammatory marker, were increased in the plasma, liver and spleen. All of these findings provide insight into the observed toxicological effect levels and tissue‐specific distribution of CdSe/CdS‐MPA QDs. Copyright © 2012 John Wiley & Sons, Ltd.     

Induction of oxidative stress in liver and kidney of rats exposed to Nigerian bonny light crude oil

The local population of Niger‐Delta in the Southern part of Nigeria have used bonny light crude oil (BLCO) as a remedy for various ailments and are exposed to some extent to this widespread environmental contaminant or its metabolites through the food chain. BLCO's hepatorenal toxicity was studied using oxidative stress indices to elucidate the precise nature and mechanism of action. BLCO was orally administered at concentrations of 0, 200, 400, and 800 mg kg^?1 to adult male rats for 7 days. After exposure, kidney weight was unaffected, but liver weight decreased significantly at 800 mg kg^?1 only compared with control. BLCO exposure resulted in dose‐dependent elevation of serum aminotransferases, total bilirubin, urea, and creatinine. Activities of superoxide dismutase and catalase decreased significantly, whereas γ‐glutamyltransferase activity and the level of glutathione increased significantly in BLCO‐treated animals compared with control in both liver and kidney of rat. Renal activities of glucose‐6‐phosphatase and 5′‐nucleotidase markedly decreased in a dose‐dependent manner in BLCO‐exposed rats. In addition, the levels of hydrogen peroxide and lipid peroxidation significantly increased, dose dependently, in liver and kidney of BLCO‐treated rats compared with control. BLCO‐treated rats showed marked degeneration of kidney evident in cortical hemorrhages, tubular necrosis, protein casts, and cellular infiltration. However, no treatment‐related liver histopathology was observed. The results suggested that BLCO elicits disruption of antioxidant status and concomitant elevation of hydrogen peroxide and lipid peroxidation differentially in liver and kidney of rats. The hepatorenal toxicity of BLCO could be due to induction of oxidative stress in liver and kidney. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2012.