Paliperidone-Associated Sialorrhea: A Case Report With Review of Current Literature.

PURPOSE/BACKGROUND: Antipsychotic-associated sialorrhea is a problematic adverse effect with potentially negative consequences on quality of life and medication adherence. While clozapine is the antipsychotic that is most associated with sialorrhea, there have been published reports of other second-generation antipsychotics associated with sialorrhea, including aripiprazole, olanzapine, quetiapine, and risperidone. Although drooling is mentioned within the package insert for paliperidone, to date there have been minimal published reports in which paliperidone is implicated as the offending agent. METHODS/PROCEDURES: Here, we present a case of sialorrhea in a 56-year-old man with schizoaffective disorder who had a supratherapeutic paliperidone level after both oral and intramuscular paliperidone use. FINDINGS/RESULTS: Paliperidone was ultimately cross tapered to aripiprazole, and the patient was given atropine drops and benztropine with resolution of the sialorrhea. We provide a review of the literature regarding the other available reports of paliperidone-associated sialorrhea, possible mechanisms behind pathophysiology, as well as reports from the World Health Organization and Food and Drug Administration adverse event reporting systems. IMPLICATIONS/CONCLUSIONS: Clinicians should be aware of the potential for paliperidone and other nonclozapine second-generation antipsychotics to be associated with sialorrhea, especially given the increased frequency of their use for a variety of psychiatric disorders.

Cancer-Causing Effects of Orthopaedic Metal Implants in Total Hip Arthroplasty.

BACKGROUND: Metal implants have been preferentially used in THA due to its biocompatibility, mechanical stability and durability. Yet concerns have emerged regarding their potential to release metallic ions, leading to long-term adverse effects, including carcinogenicity. This study aimed to investigate the risk of cancer development in patients with orthopaedic metal implants in total hip arthroplasty (THA). METHODS: Patients with THA conducted at a local tertiary implant centre from 2001-2008 were linked to the local cancer registry and followed up to the end of 2023. Standardized incidence ratios (SIRs) for cancer incidence and its confidence interval by Poisson distribution were calculated. Survival analysis was depicted using the Kaplan-Meier method, and the log-rank test was used to assess the differences across groups. RESULTS: The study cohort included 388 patients and 53 cancers diagnosed during follow-up, at least 5 years post THA. All-site cancer risks were increased in patients with THA (SIR: 1.97; 95% CI: 1.48-2.46), validated with chi-square analysis (chi-square = 15.2551, N = 100,388, p < 0.01). A statistically significant increase in multiple site-specific cancers including haematological cancers were identified. CONCLUSIONS: Patients with THA were found to have an increased risk for cancer compared to the general population during a mean follow-up of 16 years.

A multiplex qPCR assay for transgenes detection: A novel approach for gene doping control in horseracing using conventional laboratory setup.

Illicit administration of transgene into horses is a form of gene doping that has been a key concern in equine sports. The large number of potential performance-enhancing transgenes has demanded a cost-effective and reliable detection method. Multiplex qPCR is a relevant technique, but the cross-talking between fluorophores and high background noise limits the method sensitivity and specificity. This study reports a simpler multiplexing approach by using the same fluorophore for four hydrolysis probes each targeting one of the four transgenes: human growth hormone, insulin-like growth factor 1, equine erythropoietin and interleukin-10. Any positive findings from this multiplex qPCR assay can then be confirmed by individual qPCR assays to identify potential transgene(s). This has effectively eliminated the cross-talking issue and allowed an improved signal-to-noise than conventional multiplex qPCR assay. It has also removed the limitation imposed by the available choice of fluorophores and optical channels of qPCR instruments on the number of transgenes that can be analysed in a multiplex qPCR assay. This novel multiplex qPCR has been successfully validated. The estimated limits of detection were ~1500-2500 copies/mL of blood, thus demonstrating comparable sensitivity with the corresponding duplex qPCR assays. Concurring results were obtained by analysing hundreds of official blood samples provided by racehorses with this multiplex qPCR assay and the accredited individual duplex qPCR assays. This novel multiplex qPCR assay for detecting multiple transgenes is a cost-effective screening method using a conventional laboratory setup and has opened up the potential to include the testing of additional transgenes in a single assay.

Brominated diphenyl ether (BDE) levels in liver, adipose, and milk from adult and juvenile rats exposed by gavage to the DE-71 technical mixture.

Brominated diphenyl ethers (BDEs) are used as flame retardants in consumer products. Rodent studies indicate that the liver, thyroid, and nervous system of developing animals are targets of BDEs. To explore the relationship between exposure and health in developing animals, BDE accumulation in adult and juvenile rats was examined in conjunction with changes in liver weight and serum thyroxine (T4). Adult (F0) rats received the commercial BDE mixture DE-71 by gavage at doses of 0.5, 5, and 25 mg kg(-1) body weight (bw)/day for 21 weeks. F0 rats were mated and exposure continued throughout breeding, pregnancy, lactation, and postweaning until the pups (F1 generation) reached postnatal day (PND) 42. Milk was collected from lactating dams. Adipose and liver samples were collected from F0 and F1 males and females for BDE congener analysis. Congener prevalence in rat tissues mimicked congener prevalence in wildlife and humans. Tissue concentrations of all congeners except BDE-153 were lower than would be expected based on dose proportionality, confirming that BDE-153 has a high capacity for bioaccumulation. BDEs were transferred from maternal tissues to milk during lactation. Milk congener profiles differed from maternal tissue profiles indicating that degree of bromination and maternal sequestration influenced BDE transfer to milk. Female F1 rats accumulated more BDEs than F1 males, indicating that female rats were less able to metabolize and/or excrete BDEs. Significant effects on liver weight and serum T4 levels were observed in adults and juveniles in the middle and high dose groups, corresponding to BDE levels in the µg g(-1) range. Although it remains to be determined how human liver and thyroid are affected by exposure to much lower BDE levels, the present study confirmed that gender and reproductive status influence BDE accumulation in tissues and BDE transfer to the neonate via milk.

A novel IL-1 family cytokine, IL-33, potently activates human eosinophils.

BACKGROUND: Eosinophils are likely key cells involved in the pathogenesis of asthma and allergic diseases; however, the mechanisms that regulate eosinophil dynamics and functions in mucosal tissues are incompletely understood. IL-33, which is produced by mucosal cells, is a new member of the IL-1 cytokine family. Mice injected with IL-33 display profound mucosal eosinophilia with associated pathologic changes. Although mast cells and T(H)2 cells express the IL-33 receptor, ST2, the roles of IL-33 and ST2 in eosinophil biology are unknown. OBJECTIVES: We investigated the effects of IL-33 on human eosinophils in vitro. METHODS: Eosinophils and neutrophils were isolated from blood of normal individuals and mildly atopic patients. Real-time RT-PCR and flow cytometry were used to detect ST2. Granulocyte responses to IL-33 were monitored by superoxide anion production and by degranulation; IL-5, IL-1beta, and TNF-alpha served as controls. Eosinophil survival and cytokine production were assessed by flow cytometry and ELISA, respectively. RESULTS: ST2 mRNA and protein were detected on eosinophils. IL-33 induced eosinophil superoxide anion production and degranulation as potently as IL-5. IL-33 also increased eosinophil survival and induced production of IL-8. Anti-ST2 inhibited eosinophil responses to IL-33. Neutrophils did not express ST2, nor did they respond to IL-33. CONCLUSION: IL-33 and its receptor, ST2, may play important roles in eosinophil-mediated inflammation; they may provide new therapeutic targets for controlling mucosal eosinophilic inflammation.

Metabolic consequences of using low-dose quetiapine for insomnia in psychiatric patients.

Quetiapine is frequently prescribed for insomnia that is comorbid with psychiatric disorders, but there has been no documentation of metabolic adverse effects associated with this practice. The objective of this study was to document changes in weight, body mass index, and waist circumference that occurred when low-dose quetiapine was used at bedtime for insomnia. The study was a retrospective chart review conducted at a community mental health center. Patients were non-elderly (19-65 years old) psychiatric patients who received quetiapine at < or =200 mg at bedtime for the explicit indication of insomnia. Forty-three patients were included in the study. Weight and BMI increased by an average of 4.9 lb. (P = 0.037) and 0.8 points (P = 0.048), respectively. Males experienced statistically significant increases in weight and BMI, and Caucasians experienced a statistically significant increase in BMI. There were no significant differences between baseline and endpoint metabolic parameters when examined by baseline BMI, age category, psychiatric diagnosis, or concomitant psychotropic medication. Despite the low doses typically used when quetiapine is prescribed for insomnia, metabolic adverse effects can occur and should be considered in the overall benefit to risk analysis.

A 90-day subchronic gavage toxicity study in Fischer 344 rats with 3-methylfuran.

A 90-day gavage study was conducted with 0.0, 0.02, 0.075, 0.25, 1.0 and 4.0 mg/kg bw/day dose groups of 3-methylfuran to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects including changes in gross anatomy, histopathology, clinical biochemistry and hematology. There were significant changes in the serum clinical biochemistry markers related to liver injury where males were more affected than the females for most parameters analysed. The serum liver injury marker γ-glutamyltransferase, alanine and aspartate aminotransferases were significantly increased in males in the 4.0 mg/kg dose group. Alkaline phosphatase was increased in females and males. There were increases in both gross and histological lesions in the liver of both sexes in addition to statistical differences in female liver weights at the 4.0 mg/kg bw/day dose. Significant increases in spleen weights were found in both genders. This was accompanied by a dose-dependent atrophy of both B- and T-cell regions in which the males were more affected. There were no significant changes in male kidney weights but there was microscopically decreased protein in the proximal tubules and crowding of their nuclei in the 4.0 mg/kg bw/day dose group. There were also significant changes in the kidney serum biomarkers including various electrolytes, blood urea nitrogen, creatinine and uric acid. A small, but significant increase in female kidney weights was observed and which increase was accompanied by changes in electrolytes, kidney specific markers and a dose-dependent increase in mineralization. In both genders, amylase decreased whereas lipase increased but these were not accompanied by any histological changes in the pancreas. Histopathological changes in the liver were observed consistently in male and female rats in the 0.25 mg/kg dose group and higher. Hence, a lowest observed adverse effect level (LOAEL) of 0.25 mg/kg bw/d and a no observed adverse effect level (NOAEL) of 0.075 mg/kg bw/day are proposed for 3-methylfuran-induced hepatic lesions in this study. Benchmark dose modelling based on a BMR of 10% change in lesion incidence, generated BMDLs10 of 0.08 mg/kg bw/day in male rats and 0.05-0.17 mg/kg bw/day in female rats for increased incidence of liver lesions.

Ambulatory care preceptors' perceptions on SOAP note writing in advanced pharmacy practice experiences (APPEs).

INTRODUCTION: Descriptions of SOAP note requirements and assessment methods used during advanced pharmacy practice experiences (APPEs) are limited in the literature. This study aimed to gather information from preceptors regarding SOAP note writing and assessment methods utilized during ambulatory care APPEs. METHODS: A survey was developed and distributed to ambulatory care preceptors with data collected via Qualtrics and analyzed using descriptive statistics, Fisher's exact test to assess the significance for associations between dependent and independent variables, and the Gamma test to assess dependent variables in grading habits and feedback types. RESULTS: The survey response rate was 62% with 75% of preceptors having students write SOAP notes during APPEs. A majority of preceptors (84%) do not formally grade SOAP notes with full-time faculty being more likely to grade and provide written feedback. Half of the preceptors perceived students as either prepared or very prepared to write SOAP notes but the majority felt that students struggle with the assessment portion of the note. There were significant differences between schools in the percentage of preceptors that formally grade SOAP notes, ranging from 2 to 45%. CONCLUSIONS: Preceptors' perception of student preparedness to write SOAP notes on ambulatory APPEs was similar, despite assessment methods varying widely.

Development and Validation of a Rubric to Evaluate Diabetes SOAP Note Writing in APPE.

Objective. To develop and establish validity for a grading rubric to evaluate diabetes subjective, objective, assessment, plan (SOAP) note writing on primary care (PC) advanced pharmacy practice experiences (APPEs), and to assess reliability and student perceptions of the rubric. Methods. Ten PC APPE faculty members collaborated to develop a rubric to provide formative and summative feedback on three written SOAP notes per APPE student over a 10-month period. Correlation analyses were conducted between rubric scores and three criterion variables to assess criterion-related validity: APPE grades, Pharmaceutical Care Ability Profile Scores, and Global Impression Scores. Inter-rater and intra-rater reliability testing were completed using Cohen's kappa and Intraclass Correlation Coefficients (ICC). Student perceptions were assessed through an anonymous student survey. Results. Fifty-one students and 167 SOAP notes were evaluated using the final rubric. The mean score significantly increased from the first to second SOAP note and from the first to third SOAP note. Statistically significant positive correlations were found between final rubric scores and criterion variables. The ICC for inter-rater reliability was fair (.59) for final rubric scores and excellent for intra-rater reliability (.98 to1.00). Students responded that the rubric improved their ability (84.9%) and confidence (92.4%) to write SOAP notes. Conclusion. The rubric may be used to make valid decisions about students' SOAP note writing ability and may increase their confidence in this area. The use of the rubric allows for greater reliability among multiple graders, supporting grading consistency.

Evidence-based review of the black-box warning for droperidol.

PURPOSE: Data collected from the Food and Drug Administration (FDA) under the Freedom of Information Act are presented to help clinicians understand the data prompting the black-box warning for droperidol and to make educated decisions regarding the use of droperidol and alternative agents. SUMMARY: A written request was submitted to FDA to provide a report of any and all reports of cardiovascular adverse events related to droperidol that were part of the decision to add a black-box warning to the label of droperidol. The report listed 277 cases of adverse effects associated with droperidol since its introduction to the market in 1970. Many of the reports were duplicates, leaving a total of 65 individual cases. Of these cases, only 2 described adverse effects possibly caused by droperidol in dosages commonly used in the United States. In addition to these reports, the results of two European studies prompted FDA to make the decision for the black-box warning. Both studies used droperidol doses 50-100 times higher than those used in the United States. CONCLUSION: Studies show that there is a dose-dependent increase in the rate of adverse cardiovascular events when droperidol is used either alone or in combination with other medications that cause Q-T interval prolongation. At this time, there does not appear to be significant evidence to suggest that serotonin type 3-receptor (5-HT(3)) antagonists are safer than droperidol with regard to Q-T interval prolongation. More studies are needed to determine the safety and efficacy of droperidol when used in doses of 0.625-1.25 mg compared with the 5-HT(3) antagonists.

Rectus sheath hematoma: review of 126 cases at a single institution.

Rectus sheath hematoma (RSH) is an uncommon condition characterized by abdominal pain and an abdominal wall mass. We reviewed the clinical features, treatment, and outcomes of 126 patients treated for RSH at Mayo Clinic from January 1, 1992, to December 31, 2002. Most patients (64%) were women and the mean +/- SD age was 67.9 +/- 16.5 years. Most patients (69%) were on some form of anticoagulation therapy. The mean international normalized ratio was 2.6 +/- 2.4, and mean activated partial thromboplastin time was 64.2 +/- 42.7 seconds. No patients were pregnant or had a peritoneal dialysis catheter at the time of diagnosis. Approximately half of the patients (48%) had nonsurgical abdominal trauma around the time of diagnosis, with 37 patients (29%) having a cough. The most common presenting signs and symptoms were abdominal pain (84%) and an abdominal wall mass (63%). CT of the abdomen and pelvis was the most commonly used method to establish the diagnosis (83%). Most patients (86%) were successfully treated with symptom management and blood transfusion. Ten patients (7.9%) underwent surgery or endovascular embolization of bleeding vessels, and 2 patients (1.6%) died as a result of RSH bleeding. Although RSH is rarely fatal, the clinician should be aware of important risk factors that lead to RSH including female sex, older age, anticoagulation therapy, and cough or other abdominal trauma. Rapid diagnosis with directed history, physical examination, and CT of the abdomen and pelvis may help decrease unnecessary laparotomy and lead to better triage of patients who present with RSH.

Further examination of the effects of nitrosylation on Alternaria alternata mycotoxin mutagenicity in vitro.

Previously, Alternaria extract and metabolite mutagenicities+/-nitrosylation were characterized using Ames Salmonella strains TA98 and TA100, which are both reverted at GC sites. To examine other targets for mutation, the metabolites Altertoxin I (ATX I), Altenuene (ALT), Alternariol (AOH), Alternariol monomethyl ether (AME), Tentoxin (TENT), Tenuazonic acid (TA) and Radicinin (RAD) were reexamined+/-nitrosylation, using Ames Salmonella strain TA97, sensitive to frameshift mutations at a run of C's, as well as strains TA102 and TA104, reverted by base pair mutations at AT sites and more sensitive to oxidative damage. ATX I was also assessed for mammalian mutagenicity at the Hprt gene locus in Chinese hamster V79 lung fibroblasts and rat hepatoma H4IIE cells. When tested from 1 to 100 microg/plate without nitrosylation, ATX I was mutagenic in TA102+/-rat liver S9 for activation and weakly mutagenic in TA104+/-S9, demonstrating direct-acting AT base pair mutagenicity. AOH was also directly mutagenic at AT sites in TA102+/-S9 while AME was weakly mutagenic in TA102+/-S9 and TA104+S9. Nitrosylation of ATX I enhanced mutagenicity at AT sites in TA104+/-S9 but produced little change in TA102+/-S9 compared to native ATX I. However, nitrosylated ATX I generated a potent direct-acting frameshift mutagen at C sites in TA97+/-S9. While ATX I was not mutagenic in either V79 cells or H4IIE cells, 5 and 10 microg/ml nitrosylated ATX I produced a doubling of 6-thioguanine resistant V79 colonies and 0.5 and 1 microg/ml were mutagenic to H4IIE cells, becoming toxic at higher concentrations. These results suggest ATX I, AME and AOH induce mutations at AT sites, possibly through oxidative damage, with nitrosylation enhancing ATX I frameshift mutagenicity at runs of C's. Nitrosylated ATX I was also directly mutagenic in mammalian test systems.

Autopsy data and their total evaluation.

The role of the autopsy is discussed in the study of the etiology of the current major causes of death (cardiovascular and neoplastic diseases) in developed countries. Evidence is accumulating for the importance of environmental factors in the etiology of these diseases. The study of regional differences in occurrence is described as a method of identifying specific factors. Maps are shown of mortality rates for all causes of death in Ontario counties for males aged 65-74 and 95+ during 1964-68. Some of the difficulties in obtaining data in this form, and in their analysis, are indicated. Regional mortality patterns can be interpreted by the use of associations with available regional socioeconomic measures, or by the use of regional data on trace-metal levels in autopsy samples of human lung, rib, vertebra, kidney and liver. The methodology and the difficulties involved in the determination of trace-metal levels in these tissues are discussed, as is the possible relevance of these levels to the study of degenerative diseases. All these considerations emphasize the valuable contributions of autopsy studies.

Physicochemical characterization of direct fluorescent antibody reagents.

When the data from performance and physicochemical studies of conjugates are combined for analysis, the performance data and specific titers show a direct relationship to the physicochemical data (Table 2). These reagents were prepared from the same lot of antiserum. The specific titers are very misleading without the accompanying data (Table 2). The protein concentrations range from 4 to 10 mg/ml, the F/P ratios from 10 to 30, and CASE shows gamma-globulin to constitute 30 to 100% of the protein. CASE also shows the gamma-globulin F/P ratio to be only 10 to 20. Using these data, we calculated the concentrations of the gamma-globulins and normalized their titers to 10 mg/ml. The value of good fractionation procedures for recovering gamma-globulin and the desirability of obtaining optimal F/P ratios are reflected in the adjusted titers. Physicochemical characterization of conjugates identifies superior and deficient reagents and frequently reveals the cause of inadequate performance. In this way it serves as a quide for improving reagent quality.

Optimum immunization of rabbits for Streptococcus mutans antiserum and conjugate production and studies of batch immunoabsorption methods.

By far, the most significant rises in titers were seen with the immunization protocol used in series 6. Conjugates prepared from bleedings on the 33rd day produced exceptionally high titers for type b S mutans, and reasonably high titers for type a were obtained in a short time. A concentrated antigen with Formalin (13.4 ml) was given during a ten-day period followed by a two-week rest period, after which booster doses of either antigen with Formalin or live antigen were given (Fig 1). Based on evaluation of the immunization protocol just described, series 6 resulted in the highest titered reagents, but the data are insufficient to permit recommending that particular schedule without limitations. Our experience in the use of live antigens of S mutans for immunization is limited in that only types b, c, and e have been used in this way. The rabbits survived these injections, but the pathogenicity of other strains and other serotypes has not been determined. In addition, protocols including combined injections of killed and living organisms should be tested further for possible improvement in antibody production. In view of these considerations, our recommendations for production of high titered antiserums for S mutans in rabbits are as follows: -Take a preimmunization bleeding from each rabbit and screen by indirect FA tests with the antigens to be used. -Inject heavy concentrations (40 IU/ml) of Formalin-killed cells, intravenously. -Inject for eight to ten consecutive days, giving increasing doses of antigen ranging from 0.2 to 5.0 ml for a total of 12 to 15 ml. -Rest the rabbits for one week. If you are monitoring the progress of immunization, bleed the rabbits before giving booster injections. -Give booster injections on four consecutive days, giving 0.25, 0.5, 1.0, and 1.5 ml of live antigen that has been washed one time to remove traces of media and adjusted to a concentration of 40 IU/ml. If live antigen is not used, continue to give booster injections with killed antigen, injecting 2.0 ml on each of three consecutive days. -Rest the rabbits for one week and take sufficient blood to produce the trial reagents needed, or exsaguinate the rabbits. Absorption of type a conjugates resulted in the total loss of titer for type a cells. The cross-reactions with type b conjugate were easily eliminated by dilution, with the exception of the cross-reaction with S sanguis JC-43. Bratthall's absorption method eliminated all cross-reactions of the type b conjugate. Absorption of type c conjugate successfully removed the cross-reaction with type e cells; however, the loss of homologous type c titer was so great that this absorption is of limited value. High-titered conjugates for types d and e have been obtained by using batch absorption procedures.

Dosing via gavage or diet for reproduction studies: a pilot study using two fat-soluble compounds-hexachlorobenzene and aroclor 1254.

The choice of a dosing route for in vivo toxicological tests is often dictated by practical constraints. Reproduction studies are particularly challenging in this regard since the determination of no-effect levels and allowable daily intakes from reproduction data encompasses exposure of the dam to the test xenobiotic prior to pregnancy, during gestation and during lactation. The fetus/infant can be exposed to the xenobiotic as well as the dam's metabolic products of the test xenobiotic during gestation and lactation. We initiated a series of two-litter, pilot reproduction studies with Sprague-Dawley and Fischer 344 rats to specifically ascertain the amount of xenobiotic and its metabolites ingested by the nursing neonate on lactation days 4, 7, 12, 17 and 21, when its dam received the xenobiotic via its diet or by gavage. The xenobiotics studied in this initial series of experiments were hexachlorobenzene (HCB) and Aroclor(R) 1254 (polychlorinated biphenyls; PCBs). The dams were dosed for 28 days, mated to untreated males and then remated approximately 2 weeks after weaning their first litter to a second untreated male. Dietary levels of 10 ppm HCB or 10 ppm PCBs, and gavage doses of 0.9 mg HCB or 0.8 mg PCBs/kg body weight/day were chosen and resulted in similar doses of HCB and PCBs per unit of the body weight of the dam during the premating period. There were no apparent toxicological effects regarding the dam nor were any of the reproduction parameters (feed consumption, dam weight, litter size, pup weight, external anomalies and day 4 viability index) significantly different from control values. Following impregnation, the body weight of the dam increased appreciably during gestation, but its feed consumption increased only slightly. During lactation, the dam's feed consumption increased markedly while its body weight increased slightly. Consequently, when dams received the xenobiotic in their diet they consumed slightly less xenobiotic per unit of body weight during gestation when compared to the gavaged dams, whereas the situation was dramatically reversed during lactation. While the greater consumption of xenobiotic by the dietary-dosed dams during lactation did result in more HCB (P

Effects elicited by toxaphene in the cynomolgus monkey (Macaca fascicularis): a pilot study.

Toxaphene, which was added to glycerol/corn oil, was administered at a level of 1 mg/kg body weight/day in gelatin capsules to four healthy young adult cynomolgus (Macaca fascicularis) monkeys for 52 weeks. Four control monkeys ingested capsules containing only glycerol/corn oil. Each group had two males and two females. On a daily basis, each monkey's feed and water consumption was determined, its health was monitored and the females were swabbed to evaluate menstrual status. On a weekly basis, each monkey's body weight was determined and a detailed clinical evaluation was performed. At 4-week intervals, blood samples were taken for serum biochemistry, haematology and toxaphene analysis. Also, a local anaesthetic was administered to the nuchal fat pad area of each monkey, and adipose samples were obtained for toxaphene analysis. 1 day prior to the biopsies, a 24-h urine and faecal collection was obtained for toxaphene analysis. After 34 weeks of treatment, the immune system of the monkeys was evaluated. After 52 weeks of dosing, all treated and two control animals were necropsied. Liver samples were obtained and microsomal fractions were prepared immediately. A portion of liver and kidney was taken for toxaphene analysis. All of the major internal organs were weighed and bone marrow evaluations were conducted. Organ and tissue samples were fixed in 10% formalin and processed for light microscopy. There was no effect of treatment on body weight gain, feed consumption, water consumption or haematological parameters. Two major clinical findings were inflammation and/or enlargement of the tarsal gland and impacted diverticulae in the upper and lower eye lids. At necropsy, the relative spleen and thymus weights were greater for the treated monkeys than the controls. Toxaphene administration produced an increase in metabolism of aminopyrene, methoxyresorufin and ethoxyresorufin, three substrates that are altered specifically by cytochrome P450-based hepatic monooxygenase enzymes. Histopathological examination of tissues was unremarkable by light microscopy. Tissue analysis for toxaphene and immunology findings have been published elsewhere.