Serum Chemistry Measurements Research Articles

N-methylformamide induces multiple organ toxicity in Fischer 344 rats.

N-Methylformamide (NMF) is a widely used chemical (CAS No.: 123-39-7) in several industries and its usage is continuously increasing. However, studies for NMF have been focused on hepatotoxicity from now. Its toxicity profile has not yet been established owing to limited toxicity data. Therefore, we evaluated systemic toxicity via NMF inhalation. We exposed 0, 30, 100, and 300ppm NMF to Fischer 344 rats for 6h/day, 5days a week for 2weeks. Clinical signs, body weights, food consumption, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathology were performed. Two females exposed to 300ppm NMF died during exposure period. Decrease of food consumption and body weight in both sexes exposed to 300ppm in females exposed to 100ppm were noted during exposure period. Increased RBC and HGB were noted in females exposed to 300ppm. A decrease in the levels of ALP and K and increase in the levels of TCHO and Na were observed in both sexes exposed to 300 and 100ppm. Increased levels of ALT, AST, BUN and decreased levels of TP, ALB, Ca were observed in females exposed to 300 and 100ppm. The relative liver weight was elevated in both sexes exposed to 300 and 100ppm NMF. Hypertrophy in the liver and submandibular glands and nasal cavity injuries were noted in both sexes exposed to 300 and 100ppm NMF. Tubular basophilia of the kidneys were noted in females exposed to 300ppm NMF. We revealed that NMF affect several organs including the kidneys not only the liver and NMF-related toxicity is predominant in female rats. These results could contribute to the development of NMF toxicity profile and may help in developing strategies for the control of occupational environmental hazards related to NMF.

Effects of relocation on immunological and physiological measures in female squirrel monkeys (Saimiri boliviensis boliviensis).

In the present study, we have quantified the effects of transport, relocation and acclimate/adapt to their new surroundings on female squirrel monkey. These responses are measured in blood samples obtained from squirrel monkeys, at different time points relative to their relocation from their old home to their new home. A group of squirrel monkeys we transported, by truck, for approximately 10 hours. Peripheral blood mononuclear cells (PBMCs) were assayed in order to evaluate the phenotype of lymphocyte subsets by flow, mitogen-specific immune responses of PBMCs in vitro, and levels of cytokines at various time points including immediately before transport, immediately upon arrival, and after approximately 150 days of acclimation. We observed significant changes in T cells and subsets, NK and B cells (CD4+, CD8+, CD4+/CD8+, CD16+, and CD20+). Mitogen specific (e.g. PHA, PWM and LPS) proliferation responses, IFN-γ by ELISPOT assay, and cytokines (IL-2, IL-4 and VEGF) significant changes were observed. Changes seen in the serum chemistry measurements mostly complement those seen in the hematology data. The specific goal was to empirically assess the effects of relocation stress in squirrel monkeys in terms of changes in the numbers and functions of various leukocyte subsets in the blood and the amount of time required for acclimating to their new environment. Such data will help to determine when newly arrived animals become available for use in research studies.

Bone regeneration by bone morphogenetic protein-2 from porous beads with leaf-stacked structure for critical-sized femur defect model in dogs.

The objective of this study was to investigate whether porous beads with a leaf-stacked scaffold loaded with bone morphogenetic protein-2, with sustained release for up to four weeks, were beneficial to a dog model of critical long bone defects and capable of promoting bone regeneration without side effects. Critical long bone defects were created in the femoral diaphyses of 21 dogs. Each critical defect was fixed with an intramedullary pin and an universal locking plate. Leaf-stacked scaffold beads were implanted into the defect, which was covered with a membrane. Nineteen samples were evaluated 4, 8, and 12 weeks after surgery using simple radiographs, serum chemistry measurements, histological staining, and gene expression analysis. Sustained bone morphogenetic protein-2 release from the leaf-stacked scaffold continued for four weeks and consistently affected the expression of early and late osteogenesis factors. The results suggest that sustained bone morphogenetic protein-2 release is effective for bone regeneration, with minimal side effects.

A 90-Day Inhalation Toxicity Study of Ethyl Formate in Rats

Ethyl formate, a volatile solvent, has insecticidal and fungicidal properties and is suggested as a potential fumigant for stored crop and fruit. Its primary contact route is through the respiratory tract; however, reliable repeated toxicological studies focusing on the inhalation route have not been published to date. Therefore, the present study was conducted to investigate the safety of a 90-day repeated inhalation exposure in rats. Forty male and 40 female rats were exposed to ethyl formate vapor via inhalation at concentrations of 0, 66, 330, and 1,320 ppm for 6 hr/day, 5 days a week for 13 weeks. Clinical signs, body weights, food consumption, urinalysis, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathological findings were compared between the control and ethyl formate-exposed groups. Locomotor activity decreased during exposure and recovered afterward in male and female rats exposed to 1,320 ppm ethyl formate. Body weight and food consumption continuously decreased in both sexes exposed to 1,320 ppm ethyl formate from week 1 or 3 compared with the control values. The increases in adrenal weight and decreases in thymus weight were noted in both sexes exposed to ethyl formate at 1,320 ppm. Degeneration, squamous metaplasia of olfactory epithelium in the nasopharyngeal tissue, or both were noted in the male and female rats at 1,320 ppm and female rats at 330 ppm ethyl formate. Taken together, our results indicate that ethyl formate-induced changes were not observed in male and female rats at 330 and 66 ppm, respectively. This indicates that exposure to ethyl formate at concentrations below 66 ppm for 90 days is relatively safe in rats. This is the first report of a full-scale repeated inhalation toxicity assessment in rats and could contribute to controlling occupational environmental hazards related to ethyl formate.

Safety and Dosing of Bevacizumab (Avastin) for the Treatment of Recurrent Respiratory Papillomatosis

Increasing evidence supports the use of laryngeal injections of the antiangiogenic agent bevacizumab (Avastin) for the adjuvant treatment of recurrent respiratory papillomatosis (RRP). A recent prospective open-label investigation, approved by the US Food and Drug Administration, employing 12.5 mg of sublesional bevacizumab demonstrated single-site efficacy without complications; however, the safety of multiple-site injections and higher dosing has not yet been reported. The primary objective of this study was to report on the safety of increased doses of bevacizumab for the treatment of RRP. Two cohorts of adult patients were evaluated. In the first group, a prospective analysis was performed on patients with a diagnosis of laryngeal RRP after t heir participation in th e initial clinical trial with a single-site lowerdose (7.5 to 12.5 mg). They received higher doses of sublesional laryngeal bevacizumab (15 to 50 mg total) with detailed physiologic, hematologic, and serum chemistry measurements performed before and after each bevacizumab injection. A second cohort of patients received sublesional laryngeal injections of bevacizumab (15 to 88 mg total) without physiologic measurements and underwent a retrospective analysis of reported complications. One hundred consecutive laryngeal injection sessions (office, 87; operating room, 13) with bevacizumab were performed in 43 patients, with a mean dose of 30 mg total per treatment (range, 15 to 88 mg). Sixty-three of the 100 sessions were accompanied by KTP laser photoangiolysis of the papilloma prior to bevacizumab injections. Eighteen patients (cohort 1) underwent detailed physiologic assessment, and no dysfunction was observed. There were no local or systemic complications of bevacizumab administration. The second group of 25 patients (cohort 2) also reported no significant local or systemic complications. Neither patient group was observed to have a local wound problem in the larynx. This investigation provides evidence that higher doses of bevacizumab are relatively safe in adult patients with laryngeal RRP. Further refinements in pharmacologic concentration and drug delivery will determine the optimal treatment regimens in the future.

Toxicity study of realgar

To investigate the toxicity of realgar and provide the scientific basis for safety use of realgar in clinic. Acute toxicity was tested by single oral administration. Chronic toxicity of realgar was tested at different dose levels (5, 10, 20, 80, 160 mg x kg(-1) x d(-1)) which correspond to 1/2, 1, 2, 8, 16 times of human dose levels. The rats were treated with the test substances through oral administration once daily for successively 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement, and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of realgar and no-observed adverse effect level (NOAEL) was evaluated. With the content of 90% total arsenic and 1.696 mg x g(-1) soluble asenic, LD50 of Realgar with oral administration was 20.5 g x kg(-1) (corresponding to 34.8 mg x kg(-1) soluble arsenic), equivalent to 12 812 times of clinical daily dose for an adult. Realgar can cause kidney toxicity or/and liver toxicity after administration for over 30, 60 or 90 days respectively. The kidney was more sensitive to realgar than liver. Based on repeated dose toxicity study, NOAELs were 160 mg x kg(-1) x d(-1) for 30 day's administration, 20 mg x kg(-1) x d(-1) for 60 day's administration, 10 mg x kg(-1) x d(-1) mg x kg(-1) x d(-1) for 90 day's administration respectively. Thus, for safety use of realgar, it is recommended that the daily doses of realgar (with soluble arsenic < or = 1.7 mg x g(-1)) for an adult of the body weight about 60 kg could be 10-160 mg depending on the variation of the treatment duration. Long term use of realgar can cause kidney and liver pathological change, so the doses and administration duration should be limited. The suggestion is as follows: realgar which contains soluble arsenic < or = 1.7 mg x g(-1) should be used less than 2 weeks at daily dose 160 mg, less than 4 weeks at the dose of 20 mg and less than 6 weeks at the dose of 10 mg.

Chronic Dosing of Mice with a Transferrin Receptor Monoclonal Antibody-Glial-Derived Neurotrophic Factor Fusion Protein

Glial-derived neurotrophic factor (GDNF) is a potential neurotrophic factor treatment of brain disorders, including Parkinson's disease. However, GDNF does not cross the blood-brain barrier (BBB). A brain-penetrating form of GDNF, which is a fusion protein of human GDNF and a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), has been engineered for the mouse and is designated the cTfRMAb-GDNF fusion protein. The present study examined the potential toxic side effects and immune response after treatment of mice with twice-weekly cTfRMAb-GDNF fusion protein at a dose of 2 mg/kg i.v. for 12 consecutive weeks. Chronic treatment with the fusion protein caused no change in body weight, no change in 23 serum chemistry measurements, and no histologic changes in brain and cerebellum, kidney, liver, spleen, heart, or pancreas. Chronic treatment caused a low-titer immune response against the fusion protein, which was directed against the variable region of the antibody part of the fusion protein, with no immune response directed against either the constant region of the antibody or against GDNF. A pharmacokinetics and brain uptake study was performed at the end of the 12 weeks of treatment. There was no change in clearance of the fusion protein mediated by the TfR in peripheral organs, and there was no change in BBB permeability to the fusion protein mediated by the TfR at the BBB. The study shows no toxic side effects from chronic cTfRMAb-GDNF systemic treatment and the absence of neutralizing antibodies in vivo.

Recovery of Genomic DNA from Residual Frozen Archival Blood Clots Suitable for Amplification and Use in Genotyping Assays

A greatly neglected source of DNA potentially useful for genetic or forensic studies is the clot remaining from blood samples collected for serum chemistry measurements. We have investigated the utility of residual clots remaining from venipunctures collected for California's Expanded Maternal Serum Alpha-Fetoprotein Screening Program. We report a protocol based on the salting out method for the extraction of DNA from samples which have been archived and frozen for up to 2.5 years. As much as 57 microg of high-quality DNA can be obtained from a 2-ml clot as determined by PicoGreen (Molecular Probes, Inc., Eugene, OR) fluorescence measurements. Quality of the purified DNA was evaluated by its ability to serve as template in polymerase chain reaction (PCR) amplifications, using primers that flank the polymorphic regions of six genes of pharmacogenetic interest distributed throughout the human genome. Sizes of the gene regions successfully amplified range from 215 bp to 2064 bp, using as little as 10 ng of template DNA. Because many genotyping protocols routinely recommend the design of amplicons in the 100-200 bp range, and 10-50 ng of template, we conclude that the clot remaining after serum has been removed from blood collected for serum chemistry measurements can serve as a reliable source of DNA for genotyping studies.

Effects of feeding a blend of grains naturally contaminated with Fusarium mycotoxins on feed intake, serum chemistry, and hematology of horses, and the efficacy of a polymeric glucomannan mycotoxin adsorbent.

The feeding of Fusarium mycotoxin-contaminated grains adversely affects the performance of swine and poultry. Very little information is available, however, on adverse effects associated with feeding these mycotoxin-contaminated grains on the performance of horses. An experiment was conducted to investigate the effects of feeding a blend of grains naturally contaminated with Fusarium mycotoxins on feed intake, serum immunoglobulin (Ig) concentrations, serum chemistry, and hematology of horses. A polymeric glucomannan mycotoxin adsorbent (GM polymer) was also tested for efficacy in preventing Fusarium mycotoxicoses. Nine mature, nonexercising, light, mixed-breed mares were assigned randomly to one of three dietary treatments for 21 d. The horses were randomly reassigned and the experiment was subsequently replicated in time following a 14-d washout interval. Feed consumed each day was a combination of up to 2.8 kg of concentrates and 5 kg of mixed timothy/alfalfa hay. The concentrates fed included the following: 1) control, 2) blend of contaminated grains (36% contaminated wheat and 53% contaminated corn), and 3) blend of contaminated grains + 0.2% GM polymer. Diets containing contaminated grains averaged 15.0 ppm of deoxynivalenol, 0.8 ppm of 15-acetyldeoxynivalenol, 9.7 ppm of fusaric acid, and 2.0 ppm of zearalenone. Feed intake by all horses fed contaminated grains was reduced (P < 0.001) compared with controls throughout the experiment. Supplementation of 0.2% GM polymer to the contaminated diet increased (P = 0.004) feed intake of horses compared with those fed the unsupplemented contaminated diet. Serum activities of gamma-glutamyltransferase were higher (P = 0.047 and 0.027) in horses fed the diet containing contaminated grain compared with those fed the control diet on d 7 and 14, but not on d 21 (P = 0.273). Supplementation of GM polymer to the contaminated diet decreased (P < 0.05) serum gamma-glutamyltransferase activities of horses compared with those fed unsupplemented contaminated diet on d 7 and 14. Other hematology and serum chemistry measurements including serum IgM, IgG, and IgA, were not affected by diet. It was concluded that the feeding of grains naturally contaminated with Fusarium mycotoxins caused a decrease in feed intake and altered serum gamma glutamyltransferase activities. The supplementation of GM polymer prevented these mycotoxin-induced adverse effects.

The effects of haemolysis on serum chemistry measurements in poultry

The effects of haemolysis on serum chemistry values in broiler and layer chickens, and in turkeys were determined using two types of serum chemistry analysers, a wet reagent analyser and a dry slide reagent analyser. The interfering effects of haemolysis were evaluated using eight levels of haemoglobin in serum analysed by the wet reagent instrument and six levels of haemoglobin in serum analysed by the dry slide reagent instrument. Nine serum chemistry analytical tests were performed on each analyser, including determination of glucose, total protein, albumin, creatine kinase, gamma-glutamyl transferase, aspartate aminotransferase, calcium, phosphorus and uric acid. The interfering effects of haemolysis varied depending on type of analyser, type of bird and the specific test. With the wet reagent chemistry analyser, the gamma-glutamyl transferase, phosphorus and uric acid analytes were most sensitive to haemoglobin interference, and the albumin, total protein and creatine kinase analytes were most resistant. With the dry slide reagent analyser, the gamma-glutamyl transferase, phosphorus, and albumin analytes were most sensitive to haemoglobin interference, and the glucose and aspartate aminotransferase analytes were most resistant. The effects of haemoglobin interference were not consistent from one type of chemistry analyser to another. The dry slide reagent analyser did not appear to resist the effects of haemoglobin interference better than the wet reagent analyser in this study. Our results suggest the need to construct interferographs for each chemistry analyser, species, and type of bird.

Hematology and clinical chemistry values of normal and euthymic hairless adult male Dunkin-Hartley guinea pigs (Cavia porcellus).

Hematology and serum chemistry measurements were performed on blood specimens from 12 male Dunkin-Hartley hairless guinea pigs Crl:IAF(HA)BR and 10 haired Dunkin-Hartley male guinea pigs Crl:(HA)BR. Significantly higher activities of alanine aminotransferase, aspartate aminotransferase, amylase, and creatine kinase were observed in the hairless guinea pigs as compared to the haired strain. Alkaline phosphatase activity was found to be lower in the hairless guinea pig. The hairless guinea pigs were found to have serum urea concentrations approximately 46% higher than the normal guinea pig strain. The erythrocytic mean cell volume of the hairless strain was found to be smaller, with a greater hemoglobin content. Hairless guinea pigs were found to have approximately 40% fewer leukocytes with a reversed lymphocyte:neutrophil ratio compared to the haired guinea pigs which had much higher lymphocyte counts.

Serum chemistry and histopathological evaluations of brown bullheads (Ameiurus nebulosus) from the Buffalo and Niagara Rivers, New York

Cholangiomas and cholangiocarcinomas were observed in brown bullheads (Ameiurus nebulosus) collected from the Buffalo and Niagara Rivers (NY) and Old Woman Creek (OH), USA. Significant increases in serum blood urea nitrogen, uric acid, triglycerides, inorganic phosphate, ALT, LDL, calcium, and iron and a significant decrease in cholesterol were found in the fish from the Buffalo and Niagara Rivers compared to the Old Woman Creek reference area. When relationships between the pathology and serum chemistry measurements were tested by correlation and discriminant function analysis, no predictive relationships were apparent.

Severe Reactions Associated With Diphtheria-Tetanus-Pertussis Vaccine: Detailed Study of Children With Seizures, Hypotonic-Hyporesponsive Episodes, High Fevers, and Persistent Crying

The pathophysiology of severe reactions to diphtheria-tetanus-pertussis (DTP)vaccine is not well understood. Active pertussis toxin in DTP vaccine has been proposed to cause severe DTP vaccine reactions. Large doses of pertussis toxin cause hyperinsulinemia and hypoglycemia as well as leukocytosis with a predominant lymphocytosis in animal models. To learn more about the causes of and risk factors for severe DTP vaccine reactions, children experiencing severe DTP vaccine reactions were studied. Prospective, referral-based surveillance. Los Angeles, CA. Children experiencing severe reactions within 48 hours of DTP immunization and evaluated within 24 hours of the reaction. Severe reactions included encephalopathy, persistent crying > or = 3 hours, hypotonic-hyporesponsive episodes (collapse episodes), fever > or = 40.5 degrees C, or seizures. Some comparisons were made between children with DTP vaccine-associated seizures and a comparison group of children experiencing febrile seizures unrelated to immunization. A history and physical examination were performed. Follow-up examinations were performed 1 month later. Blood was collected for complete blood cell count with leukocyte differential count, serum chemistry measurements, and insulin and glucose values. Serum was assayed for active pertussis toxin, both in free and immune-complex masked states. Sixty children experienced severe reactions within 48 hours of DTP immunization: 32 children had seizures only, 14 subjects had hypotonic-hyporesponsive episodes, 2 subjects had fever > or = 40.5 degrees C only, 4 subjects had persistent crying > or = 3 hours, 6 children had seizures and fever > or = 40.5 degrees C, and 2 children had persistent crying and seizures. The children with seizures had a high rate of personal and family histories of seizures, and 90% had documented fevers (> or = 38 degrees C). Persistent crying was associated with painful local reactions. Effects that may have been due to vaccine pertussis toxin were not found. Lymphocytosis did not occur, nor did hypoglycemia. Some relatively elevated insulin values were noted; however, this finding was also noted in the comparison group of children experiencing febrile seizures unrelated to immunization. No biologically active pertussis toxin was found in the acute sera of children experiencing severe DTP vaccine reactions. Seizures associated with DTP vaccine have similar clinical characteristics as febrile seizures, and persistent crying is initiated by painful local reactions. Vaccine endotoxin is a cause of febrile DTP vaccine reactions. We found no evidence that DTP vaccine pertussis toxin plays a role in severe DTP vaccine reactions.

Blood serum chemistry measurements of normal and acutely stressed channel catfish

1. 1. An automated blood serum chemistry analytical system designed for human usage was employed to establish the levels of 26 different components present in sera obtained from various experimental groups of channel catfish. 2. 2. Comparisons of samples from feral and commercial production pond fish during warm months indicated statistically significant differences in the serum levels of sodium, CO 2 urea nitrogen, direct bilirubin, cholesterol, creatinine and protein. 3. 3. Laboratory acclimated and production pond fish exhibited differences in serum electrolytes (sodium, potassium, chloride, phosphorus), serum metabolites (urea nitrogen, creatinine, triglycerides), serum enzymes [γ-glutamyl transferase, glutamate-oxaloacetate transaminase (GOT), lactate dehydrogenase (LDH), alkaline phosphatase, and amylase], and serum iron. 4. 4. Seasonal (temperature?) differences in production pond fish were noted for 12 serum components including potassium, magnesium, CO 2, glucose, creatinine, albumin, iron, alkaline phosphatase, and glutamate-pyruvate transaminase (GPT). 5. 5. Comparisons of samples obtained from laboratory-acclimated fish before and 18 hours after acute handling and transport stress revealed significant differences in only three serum parameters: glucose, LDH, and creatine phosphokinase (CPK). 6. 6. These studies suggest that “normal” values established by any method of sera analysis may be different in the same species depending on the diet, season, and presence of environmental stressors.

Enhancement of the Hepatotoxicity of Chloroform in B6C3F1 Mice by Corn Oil: Implications for Chloroform Carcinogenesis

A recent study of the ability of chloroform in drinking water to produce cancer reported that male Osborne-Mendel rats developed renal tumors, but that female B6C3F1 mice failed to develop hepatocellular carcinomas. The results obtained in the male Osborne-Mendel rats were comparable to those observed in an earlier study sponsored by the National Cancer Institute (NCI). On the other hand, the lack of an increased incidence of hepatocellular carcinomas in female B6C3F1 mice was in sharp contrast to previously reported results. The doses of chloroform used were comparable to that which produced an 85% incidence in the NCI study. We have investigated the extent to which the vehicle might be responsible for the different results in these two studies by examining the differential effects of chloroform when it was administered by gavage using corn oil versus a 2% Emulphor suspension as the vehicle. Male and female B6C3F1 mice were administered chloroform at 60, 130, and 270 mg/kg per day for 90 days. At sacrifice, body and organ weights were measured, and blood was recovered to perform the following serum chemistry measurements (in order of priority): glutamate oxalacetate transaminase (SGOT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and triglyceride (TG) levels. The liver was sectioned for histopathological examination. Chloroform increased SGOT levels significantly only when administered in corn oil at a dose of 270 mg/kg in both male and female mice. It had no effect on LDH activity. There was a small increase in BUN when chloroform was administered in corn oil, but not when administered in 2% Emulphor. When administered in corn oil, chloroform significantly decreased serum TG levels but was without effect on this parameter when administered in 2% Emulphor. Chloroform decreased body weight and increased liver weight with both vehicles, but the effects were significantly greater when it was administered in corn oil. Mice administered chloroform in corn oil displayed a significant degree of diffuse parenchymal degeneration (5 of 10 males and 1 of 10 females) and mild to moderate early cirrhosis (5 of 10 males and 9 of 10 females); significant pathological lesions were not observed in the animals administered corn oil without chloroform nor in mice receiving chloroform in 2% Emulphor. These data indicate that administration of chloroform by corn oil gavage results in more marked hepatotoxic effects than observed when it is provided in an aqueous suspension.(ABSTRACT TRUNCATED AT 400 WORDS)

Enhancement of the hepatotoxicity of chloroform in B6C3F1 mice by corn oil: implications for chloroform carcinogenesis.

A recent study of the ability of chloroform in drinking water to produce cancer reported that male Osborne-Mendel rats developed renal tumors, but that female B6C3F1 mice failed to develop hepatocellular carcinomas. The results obtained in the male Osborne-Mendel rats were comparable to those observed in an earlier study sponsored by the National Cancer Institute (NCI). On the other hand, the lack of an increased incidence of hepatocellular carcinomas in female B6C3F1 mice was in sharp contrast to previously reported results. The doses of chloroform used were comparable to that which produced an 85% incidence in the NCI study. We have investigated the extent to which the vehicle might be responsible for the different results in these two studies by examining the differential effects of chloroform when it was administered by gavage using corn oil versus a 2% Emulphor suspension as the vehicle. Male and female B6C3F1 mice were administered chloroform at 60, 130, and 270 mg/kg per day for 90 days. At sacrifice, body and organ weights were measured, and blood was recovered to perform the following serum chemistry measurements (in order of priority): glutamate oxalacetate transaminase (SGOT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and triglyceride (TG) levels. The liver was sectioned for histopathological examination. Chloroform increased SGOT levels significantly only when administered in corn oil at a dose of 270 mg/kg in both male and female mice. It had no effect on LDH activity. There was a small increase in BUN when chloroform was administered in corn oil, but not when administered in 2% Emulphor. When administered in corn oil, chloroform significantly decreased serum TG levels but was without effect on this parameter when administered in 2% Emulphor. Chloroform decreased body weight and increased liver weight with both vehicles, but the effects were significantly greater when it was administered in corn oil. Mice administered chloroform in corn oil displayed a significant degree of diffuse parenchymal degeneration (5 of 10 males and 1 of 10 females) and mild to moderate early cirrhosis (5 of 10 males and 9 of 10 females); significant pathological lesions were not observed in the animals administered corn oil without chloroform nor in mice receiving chloroform in 2% Emulphor. These data indicate that administration of chloroform by corn oil gavage results in more marked hepatotoxic effects than observed when it is provided in an aqueous suspension.(ABSTRACT TRUNCATED AT 400 WORDS)

Hematology and clinical chemistry values in the killer whale, Orcinus orca L.

Clinical hematology and blood chemistry values are reported for the killer whale. These represent a panel of 13 hematological and 21 serum chemistry measurements determined on killer whales maintained for display at Sea World facilities. The values have been collected over a 10-yr period from 14 active, clinically normal individuals, six males and eight females. The cumulative normal values for each of these animals fall into well-defined clusters from which central tendencies and the range of values can be established. No significant male-female differences were observed for any measurement. There were consistent differences among the killer whales in hemoglobin, hematocrit and red blood cell count. A decrease in total white blood cell counts was associated with age and/or changes in parasite loads. Younger animals exhibited higher glucose levels and lower total protein levels. Serum urea nitrogen (BUN) and creatinine were elevated in older and larger males. Lactic dehydrogenase activity was lower in all animals of Pacific origin, as compared to animals from the Atlantic, regardless of age or sex. These "normal" differences emphasize the importance of establishing an animal's individual hematologic and blood chemistry profile by routine sampling.