Effects of Subchronic Inhalation Exposure of Mice to a High-Boiling Coal Liquid

Effects of Subchronic Inhalation Exposure of Mice to a High-BoilingCoal Liquid. SPRINGER, D. L., MILLER, R. A., WRIGHT, C. W.,RAGAN. H. A., BUSCHBOM, R. L., AND MAHLUM, D. D. (1987). Fundam.Appl. Toxicol. 9,277–286. Mice (CD-1) were exposed toaerosol concentrations of 0.0, 0.03, 0.14, or 0.69 mg/literof heavy distillate (HD), a high-boiling coal liquid from thesolvent-refined coal (SRC)-II process. Exposures were for 6hr/day, 5 days/week for 13 weeks. Particle sizes ranged between1.6 and 1.8 µm, mass median aerodynamic diameter, witha geometric standard deviation range of 1.9–2.5. Growthfor high-dose males was significantly less than that of thecontrol group. Compared to controls, weights of liver were significantlyhigher and those of ovaries and thymus significantly lower,these changes were significant on both absolute and relativeweight bases. The number of red blood cells, volume of packedred cells, and hemoglobin concentration for animals from thehigh-dose group were significantly lower than those of controls.Microscopic examination of organ sections showed focal hepaticnecrosis and nonspecific hepatopathy. Additionally, olfactoryepithelial degeneration occurred in a dose-dependent manner.Results from this study indicated that exposure to HD causedadverse effects at the high dose and that these changes wereeither less severe or absent in middle-dose group mice. Comparisonof these results with those for rats indicated that with ratsthe biological effects were more severe and present at lowerdoses than was observed for mice.     

Adverse Male Reproductive Effects following Subchronic Exposure of Rats to Sodium Dichloroacetate

Dichloroacetate (DCA) activates the pyruvate dehydrogenase complexenhancing carbohydrate and lactate utilization in animals. Asa result it is used clinically in the treatment of acute lacticacidosis and has therapeutic potential in the treatment of stroke.Adverse effects of chronic DCA treatment include poly-neuropathyand testicular degeneration. Since DCA is a principal productof the aqueous chlorination of fulvic acids concern has arisenregarding the agent's impact on environmental health. We treatedmale Long-Evans rats with 0, 31.25, 62.5, or 125 mg DCA/kg/dayby oral gavage for 10 weeks. Compared to controls, preputialgland and epididymis weights were reduced at 31.25 mg/kg, bodyand liver weights at 62.5 mg/kg, and accessory organ weightsat 125 mg/kg. Epididymal sperm counts were reduced and spermmorphology was impacted at the 62.5 and 125 mg/kg doses levels.Histologic examination of the testis and epididymis revealedinhibited spermiation in testes at the 125 mg/kg dose level.Computer-assisted sperm motion analysis revealed reductionsin percentage motile sperm, curvilinear and straight-line velocity,linearity, and amplitude of lateral head displacement at boththe 62.5 and the 125 mg/kg dose levels. In the assessment offertility after an overnight mating, the number of viable implantson Day 14 of gestation was decreased only in the highest dosegroup. These studies demonstrate adverse effects of NaDCA treatmenton the rat male reproductive system, primarily on the accessoryorgans and sperm within them at lower doses (31.25 and 62.5mg/kg), and on the testis at the highest dOSe (125 mg/kg).     

Postnatal Toxicity following Prenatal Reserpine Exposure in Rats: Effects of Dose and Dosing Schedule

Postnatal Toxicity following Prenatal Reserpine Exposure inRats: Effects of Dose and Dosing Schedule. BUELKE-SAM, J., KIMMEL,G. L., WEBB, P. J., SUKKER, W., JR., NEWPORT, G. D., NELSON,C. J., AND KIMMEL, C. A. (1984). Fundam. Appl. Toxicol. 4, 983–991.Pregnant CD rats were treated subcutaneously with 0, 0.1, 0.33,or 1.0 mg reserpine/kg/day either on Days 12–15 or onDays 16–19 of gestation. Dams were allowed to deliverand litters (4 ± 1 of each sex) were weighed weekly andheld to 21 days of age. Basal ornithine decarboxylase (ODC)activity and neurocheraical determinations were made on heartsand brains, respectively, from pups culled from litters on postnatalDay 1, and from two males and two females/litter at 21 daysof age. Following both treatment schedules, the high dose ofreserpine resulted in maternal weight loss during dosing, increasedstillborn pups, reduced pup weight at birth, retarded postnatalgrowth, and decreased survival to 21 days of age. Basal cardiacODC activity was reduced to 33% of control levels only on PostnatalDay 1 in both high-dose groups, while absolute heart weightdecreased and relative heart weight increased in these pups.Whole-brain concentrations of two neurotransmitter metabolites,3–4-dihydroxy-phenylacctic acid (DOPAC) and 5-hydroxyindoleaceticacid (5-HIAA), were increased only at Postnatal Day 1 in thehigh dose group treated on Days 12–15 of gestation. Noother changes were found in concentrations of these metabolitesor in the transmitters dopamine and serotonin. The only effectfound following administration of 0.33 mg/kg reserpine was areduction in maternal weight gained during both dosing periods.No signs of toxicity were observed following low-dose exposureon either schedule. Most previously reported postnatal functionalstudies following reserpine exposure have used mid- to late-gestationaltreatment with 1.0 mg/kg, a dose shown here to result in markedovert maternal and fetal toxicity. Such overt toxicity raisesthe question of whetheT the functional effects of reserpineare primary or may be secondary to general toxic effects. Suchquestions must be considered when interpreting postnatal functionaldata and in the design of further studies.     

Assessment of Toxicity of o-Nitrochlorobenzene in Rats following a 4-Week Inhalation Exposure

Assessment of Toxicity of o-Nitrochlorobenzene in Rats followinga 4-Week Inhalation Exposure. NAIR, R.S., JOHANNSEN, F.R., LEVINSKAS,G.J., AND TERRILL, J.B. (1986). Fundam. Appl. Toxicol. 7, 609-614.o-Nitrochlorobenzene (ONCB) is a chemical intermediate usedfor the synthesis of various industrial chemicals. To evaluatethe subchronic toxicity of this compound, three groups of 15male and 15 female Sprague-Dawley rats were exposed to ONCBvapor 6 hr/day, 5 days/week for 4 weeks at target concentrationsof 10, 30, or 60 mg/m³. A control group of 15 animals/sex wasexposed to room air in a separate inhalation chamber. Concentrationsof ONCB in the chambers were determined at least three timesa day using a uv spectrophotometer. Parameters monitored inthis study included observation for signs of toxicity, bodyweights, ophthalmoscopic exam, hematology, and clinical chemistry.At necropsy, selected organ weights were recorded and over 35tissues/animal were examined microscopically for all controland high-exposure level animals. No mortality was observed inthis study. Mean body weights of all groups were comparableto controls. Animals exposed to the mid and high concentrationsof ONCB showed a significant increase in blood methemoglobinand a significant decrease in hemoglobin, hematocrit, and redblood cell counts. Spleen and liver weights (absolute and relativeto body weight) were significantly increased for these two groups.Microscopic changes, observed only in the spleen, included increaseddegree of extramedullary hematopoiesis and hemosiderosis. Thesedata suggest that the toxicity of ONCB is comparable to thatof its structural analog, p-nitrochlorobenzene. Thus these twocompounds should have similar workplace exposure limits.     

Mercapturic Acid Excretion by Rats following Inhalation Exposure to m1,3-Dichloropropene

Mercapturic Acid Excretion by Rats following Acute InhalationExposure to 1,3-Dichloro-propcne. Fisher, G. D., and Kjlgore,W. W. (1988). Fundam Appl. Toxicol. 11, 300–307. Ratswere exposed to 1,3-dichloropropene (DCP), a commonly used agriculturalnematicide, by inhalation to assess the relationship betweenDCP concentration and the urinary excretion of the mercapturicacid of cis-DCP (3C-NAC). The nose-only exposure system thatwas used for simultaneously exposing up to four rodents is described.This apparatus provided for generation and monitoring of relativehumidity and test vapor concentration. Animals were exposedfor 1 hr to concentrations of up to 789 ppm DCP. Urine was collectedfor 24 hr after exposure. The quantity of 3C-NAC contained inthe urine collections exhibited an exposure concentration-dependentincrease from 0 to 284 ppm DCP. However, the amount of 3C-NACwas no greater for animals exposed to 398 or 789 ppm DCP thanfor animals exposed to 284 ppm DCP. C 1988 Society of Toxicology     

Behavioral Effects of Pre-and Postnatal Exposure to a Mixture of Low Chlorinated PCBs in Rats

Behavioral Effects of Pre- and Postnatal Exposure to a Mixtureof Low Chlorinated PCBs in Rats. LILIENTHAL, H., NEUF, M., MUNOZ,C, AND WINNEKE, G. (1990). Fundam. Appl. Toxicol. 15, 457–467.Polychlorinated biphenyl (PCB)-treated Wistar rats were testedon three different behavioral paradigms. Animals were pre- andpostnatally exposed to a technical mixture of PCBs with a chlorinecontent of 42%. Exposure levels were 0, 5, or 30 mg/kg diet.These conditions did not affect the health of the dams, thelitter size or weight, or the physical development of the offspring.Relative liver weights in the offspring, however, were elevatedin a dose-dependent manner. Open-field ambulation, active avoidancelearning, and operant conditioning on a fixed interval 30-secschedule (FI-30-sec) were used to evaluate PCB-induced behavioralalterations. Ambulation was increased in 30-mg-treated ratsat Day 22, but not at Day 120. There were more avoidance responsesand intertrial responses in the 30-mg group than in both othergroups. On the FI-30-sec schedule slightly more reactions wereemitted by the 30-mg group during the first 10 sec of the intervalthan by the other animals. More pronounced, however, were thedifferences between groups in the temporal pattern of responseswithin the 30-sec interval. It is concluded that in rats PCBexposure causes consistent alterations in all of the testedactivity-dependent behaviors.     

Acute Effects of 10-Minute Exposure to Hydrogen Fluoride in Rats and Derivation of a Short-Term Exposure Limit for Humans

A series of acute inhalation exposures of female rats was conducted with hydrogen fluoride (HF) to establish a concentration–response curve for nonlethal exposures. Durations of 2 and 10 min were used to simulate possible short-term exposures. Concentrations of HF ranged from 593 to 8621 ppm for 2-min exposures and from 135 to 1764 ppm for 10-min exposures. Additional exposures were performed for 60 min at 20 and 48 ppm HF for comparison to existing Emergency Response Planning Guidelines. Animals were evaluated on the day after exposure for changes in parameters of bronchoalveolar lavage, pulmonary function, hematology, serum chemistry, body weight, organ weights, and histopathology. Most exposures were performed with orally cannulated animals to bypass absorption of HF in the nose and achieve maximum delivery of HF to the lower airways. One of the primary uses of the resulting data was to estimate a concentration to which most people could be exposed for 10 min without severe or irreversible health effects. This level was 130 ppm. It was predicted that irritation would occur at this concentration, but the effects on the respiratory tract would not be “serious” and would be expected to be reversible. The results of this experiment and the subsequent analysis of the data provide an important aid in the planning of responses to an accidental release of HF.     

Cardiovascular Responses to Short-Term Fumonisin Exposure in Swine

The cardiovascular effects of the mycotoxin fumonisin were examinedin male cross-bred pigs fed 20 mg/kg of fumonisincontainingculture material for 7 days. On Day 8, pigs were anesthetizedwith halothane and surgically catheterized. Cardiovascular measurementsand blood gas analyses were obtained during halothane anesthesiaand 18 hr after recovery from anesthesia. Pigs fed fumonisinhad significant (p<0.05) decreases in maximal rate of changeof left ventricular pressure, heart rate, cardiac output, andmean aortic pressure, a significant increase in mean pulmonaryartery pressure and pulmonary vascular resistance, and no changein left ventricular end-diastolic pressure, pulmonary wedgepressure, and central venous pressure. Treated pigs also hadsignificant decreases in both arterial and mixed venous bloodO₂ tension, and systemic oxygen delivery, but significantlyincreased oxygen consumption and oxygen extraction ratio. Theseresults suggest that fumonisin increases oxygen consumptionand is a negative inotropic and chronotropic agent in pigs.Because fumonisin is a naturally occurring inhibitor of theenzyme sphingosine N-acyltransferase, thereby increasing sphingosineconcentrations in vivo, we speculate that the observed cardiovasculareffects were mediated in part by a fumonisin-induced increasein tissue sphingosine concentrations.     

Effects of Lead Exposure on Skeletal Development in Rats

The effects of lead on growth in female rats and on growth andskeletal development in their offspring were investigated. Noalteration in growth rate, compared to the growth rate in pair-fedcontrols, was observed in 48 weanling females continuously exposedto 250 or 1000 ppm lead in drinking water and fed a repletediet. After 49 days of exposure, all rats (24 pair-fed controls,12 exposed to 250 ppm lead, and 12 exposed to 1000 ppm lead)were mated with control males. At parturition, six lactatingdams each from the 250 and 1000 ppm lead groups were removedfrom lead exposure and given control drinking water, and sixlactating dams each from the control group were given either250 or 1000 ppm lead in drinking water. Exposure conditionsfor the remaining dams in the control, 250, and 1000 ppm groupswere not changed. Maternal blood lead in the continuously lead-exposedgroups was higher at the end of lactation than prior to mating.Lead exposure prior to parturition caused greater maternal tibiallead accumulation than lead exposure after parturition. In contrast,lead exposure prior to parturition had a lesser impact on offspringtibial lead accumulation than lead exposure after parturition.Decreases in tibial calcium and phosphorus were observed indams exposed continuously to 250 or 1000 ppm lead; however,there was no apparent effect of lead on maternal growth-platemorphology or on growth-plate width. Offspring body weight wasdepressed relative to controls during suckling (Day 11) andafter weaning (Day 24) in high-dose and continuously lead-exposedgroups. Continuous lead exposure caused a greater decrease inoffspring body weight than lead exposure only prior to or afterparturition. Decreased tail length growth suggested possibleeffects of lead on tail vertebral bone growth. While tibialcalcium and phosphorus levels were not changed in the weanlings,increased weanling growth-plate width, with disruption of chondrocyteorganization, and wider metaphyseal trabeculae were observed.Although the mechanisms of these effects are not known, theresults suggest that local lead-related effects on growth-platechondrogenesis and metaphyseal mineralization may be involved.     

The Effects of Subchronic Chlorate Exposure in Sprague-Dawley Rats

ABSTRACT

Male and female Sprague-Dawley rats were exposed to drinking water containing 3.0, 12.0 or 48.0 mM sodium chlorate. The mean drinking water consumption varied between exposure groups from 100-200 ml/kg/day. Female exposure groups consistently drank more water (23-42%) than male exposure groups thereby receiving more chlorate/kg/day at every exposure level. There were no compound related deaths; however, both males and females in the high exposure groups had significant weight loss during the 90-day exposure period. Also, in these same groups females had mild but significant decreases in the following relative organ weights; adrenals, thymus and spleen, while the relative brain weight was increased. In males, the heart, kidneys and liver were mildly decreased while the brain and testes were mildly increased. Red blood cell counts and percent hematocrit were decreased in both sexes in the high dose group. Pituitary gland (pars distalis) vacuolization and thyroid gland colloid depletion were prominent in both sexes in mid and/or high dose animals. A NOAEL of 0.36 mM chlorate/kg b.w./day in males and 0.50 mM chlorate/kg b.w./day in females were established.     

Acute Exposure to Ethanol in Pregnancy-Assessment of Cardiovascular Effects in the Isolated Perfused Rat Heart

Abstract

Numerous pregnant women are exposed to ethanol. Given the marked cardiovascular changes induced by pregnancy and the known cardiac toxicity of ethanol, we conducted this study to explore the effects of pregnancy on the cardiac toxicity of ethanol. Isolated, perfused rat hearts obtained from pregnant and nonpregnant Sprague-Dawley rats were exposed to increasing doses of ethanol (0.1, 0.2, 0.4, 0.6%). Heart rate, changes in left ventricular pressure over time (dP/dt), left ventricular systolic pressure, and coronary artery flow rate were measured. Ethanol induced profound cardiac depression in all parameters. Pregnancy neither exacerbated nor attenuated this cardiac toxicity. In the isolated perfused rat heart model, pregnancy does not affect the cardiac toxicity of acute ethanol exposure.     

Central Cholinergic Receptors in Cardiovascular and Antidiuretic Effects in Rats

1. Cardiovascular and antidiuretic responses to central cholinergic stimulation were investigated in conscious water loaded rats. 2. Pressor responses and antidiuresis were observed after injections of carbachol into the third ventricle. Intraventricular injection of nicotine produced bradycardia but no significant pressor or antidiuretic effects. 3. A prior injection of hexamethonium into the third ventricle abolished the effects of nicotine but did not attenuate the blood pressure increase or antidiuresis to carbachol. A prior injection of atropine into the third ventricle blocked both of these responses to carbachol, indicating the involvement of central periventricular muscarinic receptors in the central mediation of cardiovascular changes and antidiuretic hormone (ADH) release. 4. Analysis of blood levels of ADH after injection of carbachol into the third ventricle indicated the release of ADH in concentrations which were consistent with those seen to intravenous injections of ADH which produced equivalent antidiuresis, supporting the use of the on-line rat antidiuretic assay for measuring endogenous ADH release to central stimuli. 5. To test the possible involvement of catecholaminergic mechanisms in pressor and antidiuretic effect to cholineric receptor stimulation rats, carbachol was injected into the third ventricle of rats before and 10 min after central phentolamine treatment. Both pressor and antidiuretic effects of the carbachol injections were attenuated by phentolamine, indicating a role for a-adrenoreceptors in the mediation of both responses.     

Evaluation of the Potential for Developmental Toxicity in Rats and Mice following Inhalation Exposure to Tetrahydrofuran

Sprague-Dawley rats and Swiss (CD-1) mice were exposed to 0,600, 1800, or 5000 ppm THF (a four-carbon cyclic ether, widelyused as an industrial solvent) vapors, 6 hr/day, 7 days/week(6–19 days of gestation (DG) for rats; 6–17 DG formice). Body weights of pregnant rats in the 5000 ppm group werereduced at euthanization. There were no effects on the percentageof live rat fetuses/litter or on the fetal sex ratio. Fetalbody weight was significantly reduced for the 5000 ppm group,but the incidence of abnormalities was not increased. Mice inthe 1800 and 5000 ppm groups were sedated during exposure; approximately27% of the mice in the 5000 ppm group died. Mean body and uterineweights of mice were reduced for the 1800 and 5000 ppm groupsat euthanization (18 DG), but adjusted maternal weight gainwas not affected at 1800 ppm. There was a reduction in the percentageof live fetuses/litter for the mice in 1800 and 5000 ppm groups(95% resorptions in the 5000 ppm group). Fetal weight and sexratio in mice were not affected. An increase in the incidenceof reduced sternebral ossifications was correlated to THF concentration,although differences between groups were not statistically significant.There were no increases in the incidences of other malformationsor variations. These results suggest that THF may be embryotoxicin mice, but if the conceptus survives, development as assessedby this experimental design continues in a normal fashion. Theno-observable-adverse-effect level (NOAEL) for maternal toxicitywas 1800 ppm in both rats and mice. The NOAEL for developmentaltoxicity was 1800 ppm in rats and 600 ppm in mice.     

Effects of Lead Exposure on Bromocriptine-Induced Penile Erection in Rats

Abstract: In the present work we have studied the effects of lead exposure on penile erection induced by bromocriptine. Intraperitoneal injection of bromocriptine (2, 3, 4 and 8 mg/kg) induced dose-related penile erection in rats. Maximum response was observed with 4 mg/kg of the drug. Lead exposure (as Pb-acetate in drinking water) for periods of 7, 14, 21 and 28 days decreased the bromocriptine-induced penile erection response. Higher concentrations of lead (0.05%) were shown to cause a more prominent decrease of penile erection. The same procedure for lead administration did not significantly alter penile erection induced by physostigmine (0.1 and 0.3 mg/kg, intraperitoneally). In a series of experiments, blood lead concentrations were measured 7 and 21 days after lead exposure. Significant increases of lead concentrations were found after lead exposure. It is concluded that lead can influence bromocriptine-induced penile erection.     

Effects of Subchronic Parathion Exposure on Cyclosporine Pharmacokinetics in Rats

Parathion undergoes enzymatic oxidation by hepatic cytochrome P-450 (CYP450) enzymes to the active metabolite paraoxon. Consequently, alterations in CYP450- dependent oxidation may affect the pharmacokinetics and pharmacodynamics of drugs that are metabolized in the liver. The CYP3A family is known to be responsible for the majority of cyclosporine metabolism. The aim of the present study was to assess the disposition kinetics of cyclosporine during subchronic parathion exposure. Male Wistar rats were administered either water or two different doses of parathion (1/100 LD50, 1/25 LD50; LD50 = 14 mg/kg) by gavage for 6 wk. Subsequently, rats in each experimental group received a single oral dose of cyclosporine (10 mg/kg), and serial blood samples were drawn from the carotid artery over a period of 48 h. Pharmacokinetic analysis showed that parathion increased the blood cyclosporine concentration twofold as evidenced by AUC (area under the curve), half life (t _½) and peak plasma concentration (C _max). This may be due to inhibition of cyclosporine metabolism, an interaction that may be of clinical relevance in immunosuppression therapy.     

Effects of Whole-Body VX Vapor Exposure on Lethality in Rats

Male and female rats were whole-body exposed to VX vapor in a 1000-L single-pass exposure chamber. Estimated exposure dosages producing lethal (LCT₅₀) effects in 50% of exposed male and female rats were established for 10, 60, and 240 min exposure durations. A potency comparison with GB and GF shows that VX becomes increasingly more potent than these G agents with increasing exposure duration. VX is approximately 4–30 times more potent than GB and 5–15 times more potent than GF. Gender differences in the estimated median dosages were not significant at the 10, 60, and 240 min exposure durations. An empirical toxic load model was developed and the toxic load exponent for lethality (n) in the equation Cⁿ× T = k was determined to be n = 0.92. The VX–G regeneration assay was successfully used as a biomarker for the presence of VX in the blood plasma and RBC fractions of the blood 24 h postexposure.     

A Developmental Neurotoxicity Evaluation of the Effects of Prenatal Exposure to Fluoxetine in Rats

Fluoxetine is a widely used serotonin reuptake inhibitor effectivein the treatment of depression. This experiment assessed thepotential developmental neurotoxicity of fluoxetine. Sprague-DawleyCD rats were treated once per day on Days 7–20 of gestationwith 0, 1, 5, or 12 mg/kg of fluoxetine (free base) dissolvedin distilled water. One control group received water by gavage;animals in this group were provided food and water ad libitum.The second control group (PF) also received water by gavage;animals in this group had their food and water restricted bypair-feeding and watering them to the 12 mg/kg fluoxetine group.Litters were culled to 12 after birth and offspring (male/femalepairs) were tested neurobehaviorally at three developmentalstages (preweaning, juvenile, and adult). At each stage, twopairs per litter received tests of locomotor activity, acousticstartle, and startle after administration of one of two pharmacologicalchallenges (one pair each receiving fluoxetine or apomorphine).Two pairs were also tested for spontaneous alternation, passiveavoidance, and complex learning in a water maze. At the highestdose, fluoxetine caused maternal weight loss during pregnancy,reduced litter sizes at birth, and increased neonatal mortality.No effects on long-term growth or survival were seen. Prenatalfluoxetine exposure produced no significant effects on locomotoractivity, spontaneous alternation, passive avoidance, or watermaze performance. A few scattered interactions involving treatmentgroup were obtained on startle, but no pattern of treatment-relatedchanges was evident. Regional wet and dry brain weights takenat each stage were not affected by prenatal fluoxetine exposure.The data suggest that fluoxetine is not developmentally neurotoxicin the rat.     

Cardiovascular Effects of Lovastatin in Normotensive and Spontaneously Hypertensive Rats

• 1.Lovastatin (1, 1.5, and 2 mg/kg) decreased systolic (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive rats (SHRs) and did not modify the basal values of blood pressure in normotensive rats.
• 2.Lovastatin decreased heart rate in a dose-dependent manner, and significant effects were observed in SHRs 180 min after lovastatin administration.
• 3.Lovastatin did not act as a diuretic drug at any of the doses used.
• 4.Lovastatin (10⁻⁶ M–3×10⁻⁴ M) depresses contractions evoked by KCl (80 mM) in isolated thoracic aorta from SHRs and WRs and had almost no relaxant effects on NA-induced (10⁻⁵ M) contractions.
• 5.It is concluded that the main antihypertensive mechanism of lovastatin is due to the relaxation of rat aorta by inhibiting Ca²⁺ influx through voltage-sensitive calcium channels.

     

Exposure to cyanide following a meal of cassava food

Exposure to cyanide from gari, a popular cassava food in West Africa, is implicated in the causation of ataxic polyneuropathy and amblyopia, but this has been questioned because cyanide was not detected in gari in a study. This study was carried out to determine if gari is a source of exposure to cyanide. Gari (150 g) containing cyanohydrin, from which 128 micromol of cyanide ions could be released, was dissolved in 500 ml of cold water for each of the 12 healthy subjects to drink. Concentrations of cyanide in plasma and erythrocytes were determined at baseline and following the meal at 30 min, 1 h, hourly for 4 h and two hourly for 12 h. The mean concentrations of cyanide in the plasma were 6 micromol/l (95% CI 2-10) at baseline, 12 micromol/l (95% CI 6-17) at peak and 6 micromol/l (95% CI 2-10) on return to baseline. The mean amount of cyanide absorbed into the plasma was 13 micromol (S.D. 12), while the transit time of absorbed cyanide was 7.3 h (S.D. 2.1). This study shows that exposure to cyanide follows consumption of gari, but the amount of cyanide absorbed into the plasma from a single meal is small and unlikely to cause acute intoxication. The long transit time of absorbed cyanide in the plasma suggests that frequent intake of gari could cause cyanide to accumulate in the plasma.     

Toxicity of Cyclohexanone Oxime: I. Hematotoxicity following Subacute Exposure in Rats

Toxicity of Cyclohexanone Oxime. I. Hematotoxicity followingSubacute Exposure in Rats. DERELANKO, M. J., GAD, S. C, POWERS,W. J., MULDER, S., GAVIGAN, F., AND BABICH, P. C. (1985). Fundam.Appl. Toxicol. 5, 117–127. Cyclohexanone oxime (CHO) wasgiven po to. male and female Fischer 344 rats at dose levelsof 10, 25, 75, 150, and 300 mg/kg, five times a week for a periodof 2 weeks. Control animals received distilled water. All animalsgiven intermediate dose levels (10, 25, 75, and 150 mg/kg) andone half of the animals which were dosed at the high dose (300mg/kg) as well as one half of the controls were terminated 14days after administration of the first dose. The remaining ratsreceived no treatment for an additional 14 days and were sacrificedon Day 28 of the study (recovery phase). Dose-related decreasesin erythrocyte number, hemoglobin, and hematocrit, with an accompanyingincrease in reticulocytes and circulating nucleated erythrocytes,were observed in both sexes at Day 14. Methemoglobin levels,determined only at the high dose, were elevated in both sexesat this time. Splenomegaly and hepatomegaly were observed inboth sexes at 14 and 28 days. Histopathological examinationof the spleen and bone marrow revealed dose-related erythroidhyperplasia at 14 days which subsided by Day 28. The above effectswere more pronounced in males. Erythrocyte numbers were onlyslightly depressed and reticulocytes mildly elevated in malesat Day 28. Hematological values were not statistically differentfrom controls in females at this time. These results suggestthat CHO induces oxidative damage to the erythrocyte, resultingin a hemolytic anemia accompanied by increased erythropoiesis.The toxic effects appear reversible upon cessation of exposure.