Mean Residue Levels Research Articles

Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty

Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP. This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly. Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH > or = 7 IU/l, advanced bone age > 1 year, enlarged uterus (> or = 36 mm) and testosterone level > or = 0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12. GnRH-stimulated peak LH < or = 3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding. The triptorelin 3-month depot efficiently suppresses the pituitary-gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.

Analysis of insecticide residues in honeys from apiary (Apis mellifera) and wild honey bee(Apis dorsata and Apis florea) colonies in India

SUMMARY36 honey samples collected from colonies of Apis mellifera in apiaries and from combs of the wild honey bees A. dorsata and A. florea were analysed by gas liquid chromatography for insecticide residues. More apiary honeys were contaminated with organochlorines and organophosphates, usually at higher concentrations, than were honeys produced by wild Apis species. The most common contaminants were HCH (hexachlorocyclohexane or benzenehexachloride (BHC), detected in 83.3% of samples), endosulfan (69.4%), aldrin (36.1%) and quinalphos (33.3%). Overall mean residue levels (ppb) in honey from all species and samples combined were: acephate (153.9), aldrin (1.4), chlorpyriphos (6.6), DDT (0.6), dimethoate (7.1), endosulfan (2.5), HCH (84.9), heptachlor (1.3), malathion (15.3), methyl-parathion (2.2) and quinalphos (66.3). Carbaryl (a carbamate group insecticide) was detected in one honey sample each of A. mellifera (901.8 ppb) and A. florea (800.0 ppb). The studies reflect the potential contamination of honey by agricultural chemicals.

Glutaraldehyde-treated bovine pericardium: effects of lyophilization on cytotoxicity and residual aldehydes.

This work assesses the effect of lyophilization on the cytotoxicity and residual aldehyde concentration of glutaraldehyde-treated and lyophilized bovine pericardium (group A), comparing it to conventional glutaraldehyde-treated bovine pericardium (group B). Cytotoxicity was measured by incubating a pericardium sample from each group in saline and assessing the eluant's influence on cellular growth. Residual aldehydes were measured by HPLC. Although both groups' eluants exhibited some cytotoxicity, the eluant from group A was less cytotoxic, with a cytotoxicity index (IC50(%)) of 41%. Group B eluants all had marked cytotoxic effects; cell growth was 24.15% of the negative control at the most dilute eluant concentration (6.25%). The mean residual glutaraldehyde level was less in group A than in group B (2.36 +/- 0.11 and 9.90 +/- 3.70 g/l, respectively; n=3, P < 0.05), but residual formaldehyde levels did not differ. These results demonstrate that compared with conventional glutaraldehyde-treated bovine pericardium, lyophilized pericardium is less cytotoxic, with fewer glutaraldehyde residues.

Microbial Quality of Water Supply to an Urban Community in Trinidad

A microbiological study was conducted to determine the quality of the water supply to an urban community in San Fernando proper in south Trinidad using total coliforms and thermotolerant coliforms as indicators of water pollution. The membrane filter technique was used to detect total coliforms and thermotolerant coliforms on endo agar and MFc agar, respectively. The residual chlorine levels in water from the reservoir, from standpipes along the distribution line, and from households were determined with a commercial test kit. Of a total of 104 drinking water samples obtained from households, 84 (80.8%), 56 (53.8%), and 70 (67.3%) tested positive for total coliforms, thermotolerant coliforms, and Escherichia coli, respectively. The difference was statistically significant (P < 0.05, χ2). Of the 81 water samples collected from the Water and Sewerage Authority (WASA) main supply to households, 38 (46.9%), 13 (16.0%), and 27 (33.3%) were contaminated by total coliforms, thermotolerant coliforms, and E. coli, respectively, and the difference was statistically significant (P < 0.05, χ2). Eight (20.5%) of 39 water samples from standpipes along the distribution line tested positive for total coliforms, compared with 4 (10.3%) samples testing positive for thermotolerant coliforms. All five samples of treated water obtained from the reservoir tested negative for coliforms. There was a significant difference (P = 0.004) in the mean residual chlorine levels in water from the reservoir, water from standpipes, and water from households. Similarly, as the level of residual chlorine decreased, there was a statistically significant (P = 0.004) increase in the prevalence of total coliforms in water from 0.0% (treated reservoir water) to 15.2% (standpipe) to 53.5% (household mains) to 80.0% (household drinking water). There was also a statistically significant difference (P < 0.001, χ2) in the prevalence of total coliforms in drinking water and in water from the WASA main supply to households. Of the 105 E. coli strains tested, 7 (6.7%), 16 (15.2%), and 22 (21.0%) were mucoid, hemolytic, and non–sorbitol fermenters, respectively. It was concluded that the high degree of contamination of drinking water in households poses a health hazard to consumers.

Integrated pest management and residue levels of dichlorodiphenyltrichloroethane (DDT) and hexachlorocyclohexane (HCH) in water samples from rural areas in Gujarat State, India.

The authors identified 2 rural areas for study in Gujarat State, India, on the basis of pesticide use in agriculture and vector-control programs. In rural area 1, pesticides were used in both agriculture and vector-control programs, whereas in rural area 2, they were used in agriculture only. Water samples were collected from both areas, and they were analyzed for total dichlorodiphenyltrichloroethane (DDT) and hexachlorocyclohexane (HCH) residues. The mean residue levels of total DDT in rural areas 1 and 2 were 7.56 ng/l and 4.27 ng/l, respectively. The corresponding values for HCH were 6.96 ng/l and 5.53 ng/l, respectively. Residue levels of both pesticides were significantly lower in rural area 2 than in area 1.

Trichinella spiralis-infected muscle cells: abundant RNA polymerase II in nuclear speckle domains colocalizes with nuclear antigens.

Infection of mammalian skeletal muscle cells by Trichinella spiralis causes host nuclei to become polyploid (ca. 4N) and abnormally enlarged. It has been postulated that this enlargement reflects an infection-induced elevation of host transcription. Anthelmintic treatment of T. spiralis-infected rodents with mebendazole (MBZ) causes a reduction in the size of infected cell nuclei and a significant reduction in the total RNA content of individual infected muscle cells. A monoclonal antibody to the large subunit of RNA polymerase II (Pol II) was used here to assess the effects of infection on Pol II levels in isolated infected cell nuclei. Pol II was localized to speckle domains in isolated infected cell nuclei. Similar domains have been previously localized to sites of RNA synthesis or processing. When compared to the levels in nuclei from other, uninfected host cells, speckle-localized Pol II (SL-Pol II) levels were significantly elevated in infected cell nuclei by a mean of 3.9- to 6.8-fold. Nuclear antigens (NA) recognized by antibodies against T. spiralis localized to infected cell nuclei. By use of confocal microscopy, a subpopulation of NA was found colocalized with most speckle domains defined by Pol II. MBZ treatment of chronically infected mice, which depletes NA from infected cell nuclei, caused a significant depletion of SL-Pol II from infected cell nuclei. Control nuclei had a mean of 70% more SL-Pol II than MBZ-treated nuclei. The mean residual level of Pol II in these polyploid nuclei remained elevated by 120% over the level in 2N control nuclei. These observations may indicate two distinct effects of infection on Pol II levels in host cells.

Tetracycline residue levels in cattle meat from Nairobi salughter house in Kenya

Two hundred and fifty beef samples were collected from five slaughterhouses in and around the city of Nairobi. The beef animals were sourced from various parts of the country. Samples of 50-100 grams were collected randomly from the liver, kidney and muscle of different beef carcasses. The samples collected were processed using multiresidue analytical methods that included liquid-gas partitioning and set-pat C18 cartridges chromatographic clean up. Chlortetracycline and oxytetracycline detection was done using Knauer Model 128 HPLC with an electron capture detector. Out of the 250 samples that were analyses for tetracycline residues 114 (45.6%) had detectable tetracycline residues. Of the 114 samples with detectable tetracycline residues, 60 (24%) were liver samples, 35 (14%), were kidney samples and 19 (7.6%) were muscle samples. The mean (p>0.05) residue levels of tetracycline for the five slaughterhouses studied were as follows: Athi River 1,046 micro g/kg, Dandora 594 micro g/kg, Ngong 701 micro g/kg, Kiserian 524 micro g/kg and Dagoretti 640 micro g/kg. Of the 250 samples analysed 110 (44%) had oxytetracyclines while 4 (1.6%) had chlortetracyclines. The mean residue levels of the detected tetracyclines were higher than the recommended maximum levels in edible tissues. This study indicates the presence of tetracycline residues in the various edible tissues. Regulatory authorities should ensure proper withdrawal periods before slaughter. This study indicates the presence of tetracycline residues in the various edible tissues. Regulatory authorities should ensure proper withdrawal period before slaughter of the animals.

Time of initiation of antiretroviral therapy: impact on HIV-1 viraemia. The Swiss HIV Cohort Study.

The current recommendation that patients infected with HIV-1 be treated early is based on little evidence. We examined whether the early initiation of antiretroviral treatment affects residual HIV-1 viraemia. Viraemia was measured using an assay with a detection limit of 3 HIV-1 RNA copies/ml in drug-naive patients who started antiretroviral therapy at the time of primary HIV-1 infection (PHI) (n = 10), during chronic infection without immune suppression (CD4 cell counts > or = 500/mm3; median 577) (n = 10), or after immune suppression developed (CD4 cell counts < 500/mm3; median 113) (n = 21). In 249 samples collected 24 to 120 weeks after treatment initiation, the mean proportion of samples with HIV-1 RNA levels of less than 3 copies/ml was 75% for PHI patients compared with 32 and 8% for immunocompetent and immunosuppressed chronically infected patients, respectively. Fifty per cent of PHI patients, but none of the chronically infected patients, had persistently fewer than 3 HIV-1 RNA copies/mL. PHI patients had lower residual HIV-1 RNA levels than chronically infected patients, and immunocompetent patients had lower residual HIV-1 RNA levels than immunosuppressed patients (all pairwise, P< 0.001). The mean residual HIV-1 RNA level was independently associated with the initiation of therapy during PHI and baseline CD4 cell counts (P < 0.001 for both associations). Viraemia levels are associated with clinical progression and predict virological treatment failure. The initiation of antiretroviral therapy at the time of PHI and while CD4 cell counts are high results in lower residual viraemia. These results support early antiretroviral therapy in HIV-1-infected patients.

Pesticide Residues in Agricultural Produce in Hubei Province, PR China

Pesticide residues in agricultural produce were examined in two villages of Qianjiang municipality, Hubei province, PR China. Six food groups were sampled from the fields prior to harvesting from the farmers' market and from farmers' homes. Organochlorine residues were detected in almost all examined food groups, with residue levels significantly lower than the national tolerances (MRL). Total BHC residues were on average 31.7 µg/kg and DDT 102.5 (µg/kg. Organophosphorus residues were detected in vegetable samples. Mean residue levels of phoxim and methamidophos in vegetables were 89.9 µg/kg and 36.5 µg/kg, respectively, both exceeding the MRL. Estimated daily intakes (EDIs) of pesticide residues per person, based on the six food groups sampled, were 4.88 mg for total DDT, 2.04 (µg for total BHC, and 19.33 (µg for methamidophos. The overall results show that the increased use and misuse of pesticides for crop protection in Qianjiang municipality, notably in vegetable production, have led to worrisome leve...

Pesticide Residues in Agricultural Produce in Hubei Province, PR China

Pesticide residues in agricultural produce were examined in two villages of Qianjiang municipality, Hubei province, PR China. Six food groups were sampled from the fields prior to harvesting from the farmers' market and from farmers' homes. Organochlorine residues were detected in almost all examined food groups, with residue levels significantly lower than the national tolerances (MRL). Total BHC residues were on average 31.7 µg/kg and DDT 102.5 (µg/kg. Organophosphorus residues were detected in vegetable samples. Mean residue levels of phoxim and methamidophos in vegetables were 89.9 µg/kg and 36.5 µg/kg, respectively, both exceeding the MRL.Estimated daily intakes (EDIs) of pesticide residues per person, based on the six food groups sampled, were 4.88 mg for total DDT, 2.04 (µg for total BHC, and 19.33 (µg for methamidophos. The overall results show that the increased use and misuse of pesticides for crop protection in Qianjiang municipality, notably in vegetable production, have led to worrisome levels of pesticide contamination of agricultural produce that may carry certain risks for human health.

Organochlorine pesticide residues in bovine milk from León (Spain)

Residue levels of the organochlorine pesticides (α-HCH, lindane, heptachlor-epoxide, aldrin, endrin, dieldrin, o,p′-TDE, p,p′-TDE, p,p′-DDE and p,p′-DDT) were determined in raw bovine milk and compared with the maximum levels allowed by the European Union (EU) in these foods. The highest incidence percentage of the ten insecticides measured was for lindane, followed by α-HCH and aldrin. Moreover, the highest mean residue level was for α-HCH. None of the samples analyzed exceeded the maximum levels allowed by the EU.

Monitoring organochlorines in blood of sharp‐shinned hawks (Accipiter striatus) migrating through the great lakes

AbstractBlood samples from sharp‐shinned hawks (Accipiter striatus) were collected from 1985 to 1989 during the fall migration at Hawk Cliff, Ontario, and during the spring migration at Whitefish Point, Michigan, and analyzed for organochlorine contaminants. The study was designed to investigate the potential of using blood samples from birds of prey trapped by banders as a means of estimating the organochlorine exposure of migrant birds on their breeding and wintering grounds. Mean plasma levels averaged over the entire sample were highest forp,p′‐DDE (0.28 mg/kg, wet weight), followed by total polychlorinated biphenyls (PCBs) (0.08 mg/kg, wet weight). Mean levels of DDE, mirex, oxychlordane, heptachlor expoxide, dieldrin, hexachlorobenzene, and PCBs increased significantly in hatch‐year birds from their first southward migration to their return flight the following spring as second‐year birds. Thereafter, mean residue levels of the more persistent chemicals, including DDE, oxychlordane, and PCBs, did not change significantly between seasons in adult age classes. In contrast, dieldrin and heptachlor epoxide, which have a shorter half‐time in the body, increased significantly in the blood of all age classes after each winter and decreased significantly after each breeding season. The results were interpreted in terms of the clearance rates of the compounds as well as the diet of the birds on the breeding grounds. The sharp‐shinned hawk is a useful indicator species for contaminant‐monitoring programs involving birds of prey.

Effects of DDT treatments applied for tsetse fly control on White-headed Black Chat (Thamnolaea arnoti) populations in Zimbabwe. Part II: cause of decline

Food supply, breeding success and DDT residue accumulation were investigated as possible causes for the decline of White-headed Black Chat populations in woodland sprayed for tsetse fly control. Gut contents from 21 birds were examined. A variety of invertebrates had been eaten, but ants, especiallyCamponotus spp. (Formicidae: Formicinae),Pheidole spp. (Myrmicinae), and termites, especiallyOdontotermes spp. (Isoptera: Termitidae), predominated in the dry season. In the early rains, more beetles (Coleoptera (predominantly Curculionidae)) and fewer termites were eaten. Ant and termite activity at sprayed sites in the study area was as great as or greater than that at unsprayed sites. Ants (Camponotus spp.) from sprayed sites held mean residue levels of 8.71 µg g(-1) dry weight (max. 218 µg g(-1) dry weight) total DDT, of which 67% was unaltered DDT. Termites and beetles had mean residue levels of 3.32 µg g(-1) dry weight (max. 14 µg g(-1) dry weight) and 0.92 µg g(-1) dry weight (max. 8 µg g(-1) dry weight) total DDT, of which 44% and 37% was unaltered DDT, respectively. Fledging success of White-headed Black Chats in adjacent sprayed and unsprayed areas was similar. Residues of DDT, DDD and DDE were found in all 23 chat carcasses examined. Birds collected in the dry season (July) from an area sprayed one month before contained up to 2206 µg DDT, 367 µg DDD and 578 µg DDE, g(-1) extractable lipid (86, 17 and 27 µg g(-1) dry weight, respectively). On average, residue levels were 50 times higher than in birds from the unsprayed area, and 4 times higher than in birds taken from another, recently sprayed area in the early rains (November). It is concluded that DDT spraying did not reduce availability of prey or fledging success. Initial population decline in sprayed areas was due to a lethal accumulation of DDT residues from prey, especiallyCamponotus spp. ants. Possible reasons for continued decline for 2-3 years after spraying, are discussed.

Temporal Decline of 1080 Within Meat Baits Used for Control of Wild Dogs in New South Wales.

Short- and long-term trials were conducted to determine the rate of decline of 1080 (sodium fluoroacetate) in meat baits used for poisoning wild dogs. Baits were injected with 0.2 ml of standard 1080 solution (nominal dose of 6.00 mg of pure 1080 per bait) and placed in the field. In the long-term trial, 10 baits were collected at 7 intervals between 3 h and 226 days, and analysed for residual 1080 by liquid chromatography. The recoverable 1080 content declined greatly over the first 48 days, although at 226 days all 10 baits retained some 1080. By 42.4 days the mean residual level of 1080 in the baits was predicted to be less than the theoretical LD99 for wild dogs. At the time of distribution, baits contained less than the LD50 for an average-sized eastern quoll. The LD99 for domestic cattle-dogs was predicted to be still present in baits at 72.9 days. Loss of 1080 from these baits was not correlated with rainfall, temperature or humidity. In the short-term trial, 10 baits were collected at 11 intervals up to 200 h. The recoverable 1080 content decreased by 3.09 mg (61% of the injected dose) within the first hour after injection and declined to a low of 2.70 mg at hour 50. The level of recovered 1080 then rose to 73% of the injected dose at hour 150.

Coplanar polychlorinated biphenyl residues in human adipose tissue samples from Ontario municipalities

Human adipose tissue samples obtained during autopsies in 5 Canadian municipalities within the Great Lakes basin were analysed for coplanar PCB congeners #77, #126 and #169 using gas chromatography-mass spectrometry. The mean residue levels for male and female donors in each municipality for congeners #126 and #169 were comparable with previously reported Japanese data but were higher than limited results from North America. Significant differences in congener residue levels between municipalities were seldom detected, however, residue levels for congener #126 were significantly higher in females compared to males.

Polychlorinated biphenyls and organochlorine pesticides in milk of Norwegian women during lactation

Milk samples of 14 women were analyzed for PCBs (polychlorinated biphenyls), p,p'-DDE, and HCB (hexachlorobenzene) during 11 intervals of a 120 day-lactation period. A general downward trend in residue levels was evident, and a statistically significant decline was observed for residue levels of PCBs (P less than 0.01) and HCB (P = 0.02) on the milk fat basis. Primipara (n = 9) had from 1.5 to 2.1 times higher mean residue levels than mothers nursing their second or third child (n = 9). Significant declines in residue levels during lactation of the first child were found, while no pronounced changes in residue levels were observed during lactation of the second or third child. Overall, residue levels in this study were lower than corresponding levels found earlier in Norway, and within the range of the corresponding levels found in another Norwegian human milk survey done at the same time.

DDT residues in human milk samples from Delhi, India.

Possible contamination of human milk through the excretion of DDT and its metabolites is a concern in India where DDT is widely used as an insecticide. To assess this risk milk samples collected from 60 lactating women admitted to hospitals in Delhi were quantitatively analyzed. 55 of the 60 milk samples showed evidence of residues of ppDDE (mean 0.176 + or - 0.382 ppm) opDDT (mean 0.046 + or - 0.011 ppm) and ppDDT (mean 0.122 + or - 0.434 ppm). The mean residue level in milk fat (mg/kg fat) was 7.280 + or - 23.240 1.428 + or - 2.697 and 1.597 + or - 5.936 respectively. A large variation in individual values was observed. The finding that ppDDE is the DDT metabolite excreted into human milk at the highest level is consistent with previous research. Daily intake of total DDT averaged 0.062 mg/kg of body weight--a value that is 12 times higher than the acceptable level of DDT (0.005 mg/kg/day) set by the World Health Organization. Although no harmful effects of DDT have been recorded to date in breastfed infants in India preventive measures aimed at reducing the body burden of DDT in lactating women are urged.

Organochlorine pesticide residues in chicken eggs: a survey.

One hundred and five chicken egg samples were taken from seven geographical locations in Kenya and analyzed for organochlorine pesticide residues using gas-liquid chromatography. Nine organochlorine compounds were detected: alpha- and gamma-HCH/BHC (hexachlorocyclohexane/benzene hexachloride), aldrin, dieldrin, p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], p,p'-DDD (TDE) [2,2-bis(p-chlorophenyl)-1,1-dichloroethane] (tetrachlorodiphenylethane), o,p'-DDD [2-(o-chlorophenyl)-2-(p-chlorophenyl)-1,1-dichloroethane], o,p'-DDT [2-(o-chlorophenyl)-2-(p-chlorophenyl)-1,1,1-trichloroethane], and p,p'-DDT. Eighteen of the samples contained DDT levels exceeding the practical residue limit (0.5 ppm). The mean DDT residue content was 0.68 ppm, a result influenced greatly by the high contamination in the 18 samples. Both individual and mean residue levels for other organochlorine pesticides detected were well within the respective practical residue limits.

RESIDUES OF LINDANE AND CHLORPYRIFOS IN FIREWOOD AND WOODSMOKE

Pine bark beetle insecticide treatment plots were established on the Ocala National Forest, in central Florida. Each plot consisted of five sand pine, Pinus clausa (Chapm. Ex. Engelm) Vassey ex. Sarg., trees treated with either 0.5% lindane (benzene hexachloride) or 2% chlorpyrifos (0,0-diethyl 0-(3,5,6-trichloro-2-pgridyl) phosphorothioate). After 4 months, mean residue levels ranged from 0.32 to 35.8 mg/kg for lindane and &amp;lt; 0.1 to 76.1 mg/kg for chlorpyrifos. Chlorpyrifos was more persistent in wood than lindane. In a separate laboratory study, lindane or chlorpyrifos were applied to powdered wood and then burned under controlled conditions to determine carryover in combustion products. With slow heating to 500°C (20°C/min.), 42.7% of the lindane and 28.3% of the chlorpyrifos were recovered in the smoke stream. With rapid combustion at 600°C, all lindane and chlorpyrifos residues were thermally degraded. These findings were related to the risk of burning insecticide treated wood as firewood inside houses. Even under the worst case slow burning conditions, human exposure to airborne residues would be well under “safe-sided” threshold limit values and less than 0.2% of the acceptable daily intake established by the World Health Organization.

Phenylbutazone in the horse: a review.

Phenylbutazone is an acidic, lipophilic, non-steroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, gamma-hydroxyoxyphenbutazone, account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE2. It appears to act on prostaglandin-H synthase and prostacyclin synthase, after conversion by prostaglandin-H synthase to reactive intermediates. It markedly reduces prostanoid-dependent swelling, edema, erythema, and hypersensitivity to pain in inflamed tissues. Its principal use in the horse is for treatment of soft tissue inflammation. Phenylbutazone is highly bound (greater than 98%) to plasma protein. After i.v. injection, blood levels decline with an elimination half-life of 3-10 h. The plasma kinetics of phenylbutazone may be dose dependent, with the plasma half-life increasing as the drug dosage level increases. Plasma residues of the drug at 24 h after a single i.v. dose of 2 g/450 kg average about 0.9 microgram/ml, but considerable variation occurs. If dosing is repeated, the plasma residue accumulates to give mean residual blood levels of approximately 4.5 microgram/ml on Day 5 after 4 days of dosing. Approximately similar blood levels are found after a combination of oral and i.v. dosing. Experiments on large numbers of horses in training have been undertaken to ascertain the population distributions of residual blood levels after such dosing schedules. Absorption of phenylbutazone from the gastrointestinal tract is influenced by the dose administered and the relationship of dosing to feeding. Access to hay can delay the time of peak plasma concentration to 18 h or longer. Under optimal conditions, the bioavailability of oral phenylbutazone is probably in the region of 70%. Paste preparations may be more slowly absorbed than other preparations and yield higher residual plasma levels at 24 h after dosing, but further controlled studies are required. Phenylbutazone is easily detected in the plasma and urine of horses but concentrations in saliva are low. It is quantitated for forensic purposes by HPLC. The variability of this method between laboratories is about +/- 25%. Increasing urinary pH increases the urinary concentration of phenylbutazone and its metabolites up to 200-fold.(ABSTRACT TRUNCATED AT 400 WORDS)