Nitrate In Rats Research Articles

Toxicokinetics of silver element following inhalation of silver nitrate in rats.

Silver (Ag) and its compounds are priority contaminants, for which toxicological effects are well documented, but their toxicokinetics are not fully documented for a proper risk assessment. While the toxicokinetics of insoluble Ag nanoparticles (Ag NPs) was recently documented, there is a lack of data on the kinetic behavior of the soluble form, such as one of the mostly used silver nitrate (AgNO3) form. This study aimed to better document the toxicokinetics of Ag element following inhalation of soluble AgNO3 for comparison with a previous study on the kinetics of inhaled Ag NPs using a similar experimental design. We exposed male Sprague-Dawley rats to AgNO3 during 6 continuous hours (typical of a daily worker exposure) to determine the kinetic time courses of Ag element in blood, tissues, and excreta over a 14-day period post-exposure. Only a small fraction of Ag was found in lungs following the onset of the 6-h inhalation of AgNO3 (on average (± SD) 0.3 ± 0.1% at the end of the 6-h inhalation). Blood profiles of Ag element showed peak levels right after the end of the 6-h inhalation period and levels decreased rapidly thereafter. Toxicokinetic parameter values calculated from the average blood-concentration profiles showed a mean residence time (MRT) of 135h and mean half-life (t1/2) of 94h, with AUC of 2.5mg/L × h and AUMC of 338mg/L × h2. In terms of percent of inhaled dose, highest levels of Ag in extrapulmonary organs were found in liver, which represented on average (± SD) 1.6 ± 0.6% of calculated inhaled dose followed by the kidney with 0.1 ± 0.08%. Peak levels in the GI tract (including contents) were found at the end of the 6-h inhalation and represented 20 ± 15.6% of the inhaled dose. The dominant excretion route of Ag was through feces. The time course of Ag element in the GI tract and feces following AgNO3 inhalation is also compatible with an intestinal reabsorption of Ag. When compared to results of Ag NPs of a prior study with the same design, this study showed differences in the kinetics of soluble AgNO3 compared to insoluble Ag NPs, with higher levels in blood, GI tract, and extrapulmonary tissues but lower levels in lungs following AgNO3 exposure.

Tolerance of Rodents to an Intravenous Bolus Injection of Sodium Nitrate in a High Concentration.

Simple SummaryNitrate is found in many foods and is a common metabolite that is supplied mostly through the diet. Recently, we have found that an analog of this compound, labeled with the stable isotope (non-radioactive) nitrogen-15, is a potentially useful contrast agent for magnetic resonance imaging (MRI), as it does not include a metal component as most other MRI contrast agents. This analog was previously shown with a very high magnetic resonance signal, which is relatively long-lasting, when combined with the new adjunct technology to MRI called hyperpolarization. Prior to serving as a contrast agent for MRI in patients, this agent needs to be tested and validated in small animals. As a prerequisite to such studies, one must ensure that the injection of the naturally abundant agent (not labeled with any isotopes) will be tolerated by the animals. The purpose of the current study was to evaluate the tolerance to an intravenous injection of sodium nitrate in rats and mice, as MRI contrast agents are routinely administered in this way. We have found that a high dose of sodium nitrate can be safely injected into rats and mice. This result opens the way for preclinical MRI studies with sodium nitrate.Nitrate, the inorganic anion NO3−, is found in many foods and is an endogenous mammalian metabolite, which is supplied mostly through the diet. Although much is known about the safety of sodium nitrate when given per os, methodological safety data on intravenous bolus injection of sodium nitrate to rodents are lacking. Recently, we have proposed a new use for nitrate, as a contrast agent for magnetic resonance imaging that will be metal free and leave no traces in the body and the environment further to the imaging examination. It was shown that a stable isotope-labelled analog of this ion (15NO3−), in a sodium nitrate solution form and hyperpolarized state, produces a high magnetic resonance signal with prolonged visibility. Therefore, sodium nitrate was targeted for further preclinical development in this context. In the absence of methodological safety data on the potential effects of a high concentration sodium nitrate bolus intravenous injection into rodents, we carried out such an investigation in mice and rats (n = 12 of each, 6 males and 6 females in each group, altogether 24 animals). We show here that an intravenous bolus administration of sodium nitrate at a concentration of 150 mM and a dose of 51 mg/Kg does not lead to adverse effects in mice and rats. This is the first investigation of the tolerance of rodents to an intravenous injection of sodium nitrate.

Evaluation of subchronic repeated administration toxicity of ammonium nitrate in rats.

Ammonium nitrate is a chemical mostly used in agriculture and munitions to produce fertilizers and explosives, respectively. Its annual production and consumption exceed ten million tons. Despite is diverse uses, large production and consumption, and occupational risk, information on the toxicity that results from oral exposure to ammonium nitrate is limited. In this study, the safety of ammonium nitrate was therefore evaluated by observing its subchronic toxicity in rats. Ammonium nitrate (0, 100, 300 and 1000mg/kg/day) was orally administered by gavage to rats at 5 times/week for 13weeks. Reversibility of the effects of 1000mg/kg/day was assessed in rats after 2weeks. Mortality, clinical signs, body weight, and food consumption were monitored. Hematology, serum chemistry, urinalysis, organ weight, necropsy, and histopathology were performed. Salivation was intermittently observed in both sexes receiving 300 and 1000mg/kg/day ammonium nitrate, which normalized 2weeks post-treatment. Urine volume increased in both sexes receiving 1000mg/kg/day ammonium nitrate. Urine pH decreased in both sexes of all dosing groups when compared with the concurrent control group. Urinary changes normalized 2weeks post-treatment. Blood urea nitrogen levels increased in males receiving 1000mg/kg/day, but normalized 2weeks later. Potassium level in males and sodium and chloride levels in both sexes receiving 1000mg/kg/day ammonium nitrate decreased, but normalized 2weeks later. Hypertrophy of zona glomerulosa in the adrenals was observed in both sexes receiving 1000mg/kg/day and in females receiving 300mg/kg/day ammonium nitrate. After a 2-week recovery period, the same lesion was observed in one female receiving 1000mg/kg/day ammonium nitrate. Our results indicate that ammonium nitrate induces reversible salivation, increases BUN levels, induces acidic diuresis with decreases in sodium, potassium, and chloride levels, and induces ZG hypertrophy. These results shed light on the toxicity profile of ammonium nitrate.

Effect of Repeated Oral Administration of Roundup® and Ammonium Nitrate on Liver of Wistar Rats

The present study was conducted to evaluate single and interactive toxicity potential of Roundup® and ammonium nitrate in rats for a period of 120 days. Animals of both sexes were divided into four groups of six rats each. Group I served as control and rats were provided with water only. Group II rats were treated orally with Roundup® @ 500 mg/kg b.wt. Rats of Group III were orally administered with ammonium nitrate @ 220 mg/kg b.wt. Group IV received both Roundup® @ 500 mg/kg b.wt and ammonium nitrate @ 220 mg/kg b.wt. Significant increase in plasma alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase was observed in groups II, III and IV as compared to control group I. Liver homogenates manifested significant increase in lipid peroxidation along with significantly decreased activities of superoxide dismutase, catalase and glutathione peroxidase in all treated rats as compared to control. Concomitant exposure to both of these chemicals in group IV showed more significant alterations in various biochemical and oxidative stress indices even in comparison to groups II and III. Histopathologically, Roundup® treated group II showed moderate hepatocytic degeneration and necrosis in liver. Liver in group III showed peri-central mono-nuclear cells (MNC’s) infiltration and focal area of necrosis crowded by mononuclear cells (MNC’s) and in group IV showed severe degeneration of hepatocytes with granular cytoplasm and formation of focal necrotic granuloma infiltrated by mononuclear cells (MNC’s).

Sub-acute oral toxicity of Roundup® and ammonium nitrate with special reference to oxidative stress indices in wistar rats

The aim of present study was to unravel the single and interactive toxic potential of Roundup® and ammonium nitrate in rats after their oral administration for a period of 28 days. The animals were randomly divided into four groups with six rats in each group. Group I served as control and were orally administered with water. Group II animals were orally exposed to Roundup @ 500mg/Kg/day. Animals in group III were orally treated with ammonium nitrate @ 220mg/Kg/day while as group IV received both Roundup and ammonium nitrate @ 500mg/Kg/day and 220mg/Kg/day respectively. After 28th day of treatment, blood samples were taken and analysed for various oxidative stress parameters. Significant increase in LPO was observed in group II, III and IV as compared to control. GSH decreased significantly in all treated groups in comparison to control animals. The activity of anti-oxidant enzymes SOD, CAT, GSH-Px decreased significantly in group II, III and IV as compared to group I. GST increased non significantly in group II but decreased significantly in group III and IV. Concomitant exposure to both of these chemicals in group IV showed more significant alterations in oxidative stress indices even in comparison to group II and III.

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 mgkg-1 body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO3 up to 1 mgkg-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.

Amelioration of liver and kidney functions disorders induced by sodium nitrate in rats using wheat germ oil

The purpose of this study was to evaluate the effect of sodium nitrate administration on some biochemical parameters and to explore the ability of Wheat germ oil (WGO) as a natural source of antioxidants to minimize the deleterious effects of sodium nitrate.The results showed significant increase in alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and significant decrease in butyryl cholinestersea (BChE) content in hepatic tissue in nitrate group as compared to control and wheat germ oil groups through the experimental period. Furthermore, there was a significant increase in thiobarbituric reactive substances (TBARS) accompanied by significant decrease in reduced glutathione (GSH) content in rat renal tissue after 28 and 42 days of treatment with drinking water containing sodium nitrate. Significant decrease was also observed in serum estradiol (E2) in group treated with nitrate through the experimental period. In addition, microscopically examination of renal tissue showed atrophy of glomerular tuft and congestion of renal blood vessels in nitrate treated group. Administration of WGO to rats with sodium nitrate suggesting role of WGO as a natural protective antioxidant agent in hepatic and renal tissues. WGO also stimulates estrogen secretion and inhibits oxidative damage that may be attributed to the presence of biologically active components (unsaturated fatty acids, unsaponifible matters and sterols matters) as antioxidant and cyto-protective activities.It can be concluded that WGO offers a great advantage for therapeutic purpose to minimized sodium nitrate free radical induced cell damage.

Subacute lung toxicity caused by repeated intratracheal exposure to cadmium nitrate in rats

Subacute lung toxicity caused by repeated intratracheal exposure to cadmium nitrate in rats

Heme-Induced Biomarkers Associated with Red Meat Promotion of colon Cancer Are Not Modulated by the Intake of Nitrite

Red and processed meat consumption is associated with the risk of colorectal cancer. Three hypotheses are proposed to explain this association, via heme-induced oxidation of fat, heterocyclic amines, or N-nitroso compounds. Rats have often been used to study these hypotheses, but the lack of enterosalivary cycle of nitrate in rats casts doubt on the relevance of this animal model to predict nitroso- and heme-associated human colon carcinogenesis. The present study was thus designed to clarify whether a nitrite intake that mimics the enterosalivary cycle can modulate heme-induced nitrosation and fat peroxidation. This study shows that, in contrast with the starting hypothesis, drinking water added with nitrite to mimic the salivary nitrite content did not change the effect of hemoglobin on biochemical markers linked to colon carcinogenesis, notably lipid peroxidation and cytotoxic activity in the colon of rat. However, ingested sodium nitrite increased fecal nitroso-compounds level, but their fecal concentration and their nature (iron-nitrosyl) would probably not be associated with an increased risk of cancer. We thus suggest that the rat model could be relevant for study the effect of red meat on colon carcinogenesis, in spite of the lack of nitrite in the saliva of rats.

Subacute lung injury and biological exposure monitoring after repeated intratracheal administration of cadmium nitrate in rats

Subacute lung injury and biological exposure monitoring after repeated intratracheal administration of cadmium nitrate in rats

Potential testicular toxicity of sodium nitrate in adult rats

Nitrate is a common contaminant in groundwater aquifers. Current study aimed at evaluating the potential testicular toxicity of sodium nitrate in rats. Sodium nitrate was given orally to rats at doses of 50, 100 or 200 mg/kg/day for 60 consecutive days. Sperm count and motility, daily sperm production and testis weight were significantly decreased specially at high doses. Testicular activity of lactate dehydrogenase-X, glucose-6-phosphate dehydrogenase, and acid phosphatase were inhibited in a dose-related manner. Lipid peroxides and hydrogen peroxide production were significantly increased in all treated animals. This was accompanied by inhibition of testicular activities of superoxide dismutase and glutathione peroxidase. Fifty mg/kg of sodium nitrate did not significantly alter catalase or glutathione reductase activity. Glutathione was significantly decreased by sodium nitrate in a dose-related manner. The decrease in sperm count and motility and daily sperm production was confirmed by histopathological studies which indicated chromatolysis, pyknosis and necrosis in spermatocytes. In conclusion, subchronic exposure of rats to sodium nitrate results in testicular toxicity as evidenced by decreased sperm count and motility, daily sperm production and testis weight, inhibited activity of enzyme markers of spermatogenesis and induction of histopathological changes. These effects are attributed, at least partly, to testicular oxidative stress.

Butoconazole nitrate pharmacokinetics studied by capillary electrophoresis

In view of the wide use of butoconazole nitrate in practical gynecology, a method for determining this drug in the blood of experimental animals has been developed based on capillary electrophoresis. Samples were prepared using sedimentation of plasma proteins by acetonitrile. The separation was carried out at 27°C in a quartz capillary (75 μm diameter, 65 cm working length) at 20 kV. The leading electrolyte was a phosphate buffer solution at pH 3.6. Detection was performed by spectrophotometry at 210 nm. The proposed technique was used to study the pharmacokinetics of butoconazole nitrate in rats upon a single intraperitoneal injection at a dose of 80 mg/kg. The kinetic curves of butoconazole nitrate concentration in the blood were constructed and were typical of drug removal with bile.

Acute Lethal Toxicity, Hyperkalemia Associated with Renal Injury and Hepatic Damage after Intravenous Administration of Cadmium Nitrate in Rats

Cadmium nitrate Cd(NO(3))(2) (CdN) is commonly used in Ni-Cd battery factories. The possibility of accidental exposure to CdN is great. CdN is very soluble in water compared to other Cd compounds. Therefore, acute toxicity would be expected to be quick due to rapid absorption after exposure. However, the mechanisms of CdN toxicity have not been fully elucidated. We investigated the acute lethal toxicity and harmful systemic effects of acute exposure to large doses of CdN. The lethal dose and dose-response study of the liver and kidney were determined after intravenous administration of CdN in rats. The LD(50) of CdN was determined to be 5.5 mg/kg. Doses of 2.1, 4.2, 6.3 mg/kg were selected for the dose-response study. Liver injury was induced at doses greater than 4.2 mg/kg. Severe hepatic injury occurred in the 6.3 mg/kg group, which would have been caused by acute exposure to the high concentration of Cd that exceeded the critical concentration in hepatic tissue. A remarkable decrease in urine volume in the 6.3 mg/kg group indicated acute renal failure. A decrease in creatinine clearance suggested acute glomerular dysfunction at doses greater than 4.2 mg/kg. Increases in urinary N-acetyl-beta-D-glucosaminidase/creatinine, beta(2)-microglobulin and glucose in the 6.3 mg/kg group indicated proximal tubular injury. Secretion of K ion was also severely affected by proximal tubular injury and severe decreases in urine volume, and an increase in serum K ion was identified at doses greater than 4.2 mg/kg. Thus severe hyperkalemia might be associated with the cardiac-derived lethal toxicity of CdN.

Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: Correlation with development of hypercholesterolemia

Changes in gene expression levels of hepatic sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) after a single i.v. injection of lead nitrate (LN, 100 micromol kg(-1) body weight) were examined comparatively by real time reverse transcriptase-polymerase chain reaction (RT-PCR) in male and female rats. Significant increases in the gene expression level of SREBP-2, a transcription factor for the HMGR gene, occurred at 6-12 h in male and at 24-36 h in female rats after LN-treatment. The gene expression level of HMGR, a rate-limiting enzyme for cholesterol biosynthesis, significantly increased at 3-48 h in male rats and 12-48 h in female rats. Subsequently, significant increases in the amount of hepatic total cholesterol in male and female rats were also observed at 3-48 h and 24-48 h, respectively. The present findings demonstrate that increases in gene expressions of hepatic SREBP-2 and HMGR and the amount of hepatic total cholesterol by LN occur earlier in male rats than in the females, and that increases in the gene expression level of HMGR and the amount of hepatic total cholesterol occur prior to the increase in the gene expression level of SREBP-2 in either sex of rats.

Lithium Induced Toxicity in Rats: A Hematological, Biochemical and Histopathological Study

Lithium (Li(+)) salts are commonly used in treating bipolar diseases. As physicians frequently keep the patients on long-term lithium therapy, awareness of the numerous side effects and pathogenesis of this lightest alkali metal is needed for such treatments. The current study was designed to evaluate the toxic effect of small doses of lithium nitrate in rats. In the present study we showed that the oral gavage feeding of lithium nitrate (20 mg Li/kg body wt) for 7 weeks on every alternate day to male albino wistar rats elicited a significant alterations in gross hematological values owing to hypochromic anemia and leucocytosis. Erythrocyte sedimentation rate (ESR) and clotting time depicted higher values and animals exhibited icteric condition. Serum levels of hexose, cholesterol and blood urea elevated; however, proteins depleted markedly. A significant increase in serum calcium and phosphorus has also been registered in lithium salt treated animals. The enzyme activities of alkaline phosphatase (Alpase) and acid phosphatase (Acpase) diminished depicting the disturbed general physiological status while there was a marked rise in the activities of transaminases (GOT and GPT) reflecting a stimulating transamination reaction in hepatic and renal tissues. The histopathological picture of the kidney tissues revealed many deformative alterations. Necrosis, binucleated cells and Kuffer's cells are visible in renal tissue. The epithelium lining of renal tissue was damaged and there were also some marked changes in glomerular region apart from intracellular alterations in corticomedulary region. The results of present study suggest that small doses of lithium induce toxicity in rats.

Effective Timing of Initial Administration of Ca-DTPA upon Removal of Inhaled Plutonium Nitrate in Rats.

The effective timing of an initial injection of Ca-DTPA and a subsequent early treatment on removal of inhaled plutonium nitrate was determined in rats. Plutonium nitrate inhaled rats received an intraperitoneal injection of Ca-DTPA at a daily dose of 150μmol/kg for 3 days, beginning at 0.5, 1, 2, 6, and 12h after inhalation of plutonium; a second regimen studied was injection at a daily dose of 30μmol/kg (the daily recommended dose for humans), beginning at 1h after plutonium inhalation. One group was served as the control with no treatment. During the experiment, the urine and feces were collected every day; on day 4, the rats were sacrificed and dissected to measure plutonium concentration in blood and various organs. The first administration of Ca-DTPA (150μmol/kg) at 1-6h after inhalation initiated an increase in urinary plutonium excretion during the first 24h following inhalation and also resulted in significant increases of urinary plutonium excretion up to 3 days following the treatment. The increase was measured in comparison to the urinary levels of the other two groups that initiated at 0.5h and 12h. In the group that was given 30μmol/kg Ca-DTPA, the high urinary plutonium excretion was found compared to those of the control group; however, these levels were lower than those of the group that was administered a dose of 150μmol/kg. Although the retention rates in the various organs of Ca-DTPA treatment groups varied to the corresponding organs in the control groups, the changed values were very slight. The results indicate that Ca-DTPA administration within 1-6h after exposure to plutonium is effective to increase the urinary excretion of plutonium in rats.

Efficacy of 3,4,3-LIHOPO for reducing neptunium retention in the rat after simulated wound contamination

Purpose: The ligand 3,4,3-Li(1,2-HOPO) was tested for Np removal after intramuscular injection of 237 Np nitrate in rats. Materials and methods: Two experiments were performed, one with simultaneous injection of neptunium and LIHOPO at dosages ranging from 3 to 200mumolkg -1 and the other with delayed administration of LIHOPO 30mumolkg -1 from 5min to 30min after Np injection. Results: The data obtained after simultaneous injections showed that the ligand dosage effectiveness was not linear and depended on the tissues being considered. For bones, the best results were obtained with 200 mumolkg -1 LIHOPO, where retention was reduced to 11% of controls. Maximum efficacies for removal in liver and kidney were obtained with 30mumol kg -1 LIHOPO, where retention was reduced to 39% and 1.6% of controls, respectively. At higher dosages, LIHOPO seemed to have a reverse effect on these tissues, demonstrated by a significant accumulation of the radionuclide. The delayed administration of LIHOPO dramatically decreased its efficacy. When administered 5min after Np, LIHOPO was still efficient (60%, 37%, 7% of controls in bone, liver, kidneys, respectively) but not when treatment was delayed to 30min. Conclusions: These results demonstrated that LIHOPO was able to complex Np at the wound site but not after translocation to blood.

Nitrate analysis by capillary gas chromatography

A microanalytical gas chromatographic (GC) method for the analysis of nitrate in rat urine is described. The method involves the conversion of nitrate to nitromesitylene and quantitation using 3,4-dimethylnitrobenzene as an internal standard. The nitroaromatics were separated on a wide-bore capillary column and detected with a nitrogen-phosphorus thermionic detector. The method exhibited linearity over the range of 1.0 to 1000 μ m nitrate, and the detection limit was 0.5 μ m nitrate (200-μl sample). The coefficient of variation (CV) range for intra-day precision was 2.2 to 5.8% (20 μ m level) and 3.1 to 6.5% (200 μ m level). Inter-day CVs ranged from 2.0 to 6.1% for the samples tested. The average recovery was 77% (20 μ m level) and 80% (20 μ m level). The accuracy of the GC method compared favorably with results obtained from a standard colorimetric nitrate assay. Interference by urinary chloride was eliminated by pretreatment of samples with saturated silver acetate. Both processed and unprocessed samples were stable for at least 60 days at −15°C. The procedure was used to measure urinary nitrate in rats fed a custom low-nitrate diet.

Nitrat biosynthesis in rats, ferrets and humans. Precursor studies with L-arginine

L-Arginine, the primary nitrogen source for nitric oxide synthesized by many cell types in culture and for biosynthesized nitrate in humans, is also a nitrogen source for biosynthesized nitrate in rats and ferrets. After administration of [15N2]L-arginine to rats and ferrets, [15N]NO3- was detected in urine. Escherichia coli lipopolysaccharide induced more than a 10-fold increase in urinary nitrate in rats and a parallel increase in incorporation of 15N from [15N2]L-arginine into NO3-. Bradykinin, a vasodilator which induces nitric oxide production by endothelial cells in vitro, lacked detectable effect on urinary nitrate or on incorporation of L-arginine nitrogen into nitrate in rats. A prolonged period of vasodilation brought on by an extended period of exercise increased urinary nitrate 2-fold in human subjects. In the rat, recoveries in 24 h post-dose urine collections of [15N]NO3- given i.v. and i.p. were 75 and 64% respectively, while in the ferret, recoveries of i.v. and per os [15N]NO3- doses were 49 and 34% respectively. Thus, nitrate synthesized by mammalian cells in vivo would undergo losses similar to those for exogenous nitrate.

Embryotoxic and teratogenic effects of aluminum nitrate in rats upon oral administration.

In order to determine the embryotoxic and teratogenic potential of aluminum, pregnant Sprague-Dawley rats were treated by gavage with a daily dose of 180, 360, or 720 mg/kg of aluminum nitrate from the sixth through to the fourteenth day of gestation. Fetal examinations were performed on day 20. The number of corpora lutea, total implants, and resorptions as well as the number of live and dead fetuses in the treated animals were not significantly different from the control group. Therefore, embryolethality of aluminum cannot be induced (as a measure of percent dead and resorbed fetuses). However, exposure of rats to aluminum nitrate resulted in decreased fetal body weight and increased the incidence and types of external, visceral, and skeletal malformations and variations in all the treated groups. Consequently, teratogenic effects of aluminum-nitrate administration may result in rats given high oral doses that induce concomitant maternal toxicity.