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Biomedical subjects

J G Babish

Publications and source records attributed to J G Babish.

At least 37 records · Page 2Linked to original sources

Mutagens in urine sampled repetitively from municipal refuse incinerator workers and water treatment workers.

Municipal refuse incinerator workers may be exposed to mutagenic compounds from combustion gases and particulates during plant operation, maintenance, and ash removal procedures. The frequency of mutagens was measured by the Ames assay in 3 urine samples collected from each of 37 workers in 4 refuse incinerators and 35 (control) workers from 8 water treatment plants during June-August 1990. When comparing the first urine samples contributed by workers in each cohort, incinerator workers had a significantly (p < .05) increased risk of both direct-acting mutagens and promutagens (8/37 or 22% for each mutagen type) compared with water treatment workers (2/35 or 6% for each mutagen type). Smoking within 24 h before urine sampling was not a confounder of these results. Interestingly, there was no significant (p > .05) difference for risk of urinary mutagens or promutagens between the two cohorts when comparing, respectively, the second and third urine samples from each cohort. The repeatability of demonstrating urinary mutagens in individual incinerator workers was poor, suggesting that their exposure was highly variable and/or that these workers modified their exposure (e.g., wore masks) as a consequence of being studied. Factors that influence production of mutagenic compounds during refuse incineration and subsequent worker exposure are discussed.

Adult↗

Pharmacokinetics of enrofloxacin in fingerling rainbow trout (Oncorhynchus mykiss).

The pharmacokinetics of intravenously and orally administered enrofloxacin was determined in fingerling rainbow trout (Oncorhynchus mykiss). Doses of 5 or 10 mg enrofloxacin/kg body weight were administered intravenously to 26 fish for each dose and blood was sampled over a 60-h period at 15 degrees C. Two groups of fish were treated orally with 5, 10, or 50 mg/kg (80 fish/dose at each temperature) and held at 15 degrees C or 10 degrees C during the 60-h sampling period. Following intravenous administration, the serum concentration-time data of enrofloxacin in rainbow trout were best described by a two-compartment open model for both doses of 5 and 10 mg enrofloxacin/kg. The hybrid rate constants alpha and beta did not differ between doses. The distributional phase was rapid with a half-life of 6-7 min for both doses. Overall half-lives of elimination were 24.4 h (95% CI = 20.2-30.8) and 30.4 h (24.2-41.0), respectively, for the 5- and 10-mg/kg doses. A large Vd(area) was observed following dosing of either 5 or 10 mg enrofloxacin/kg,: 3.22 and 2.56 l/kg, respectively. Whole body clearance for 5 mg/kg was 92 ml/h.kg and 58 ml/h.kg at the 10-mg/kg dose. Following oral administration, the serum concentration-time data for enrofloxacin were best described as a one-compartment open model with first-order absorption and elimination. Apparent Ka over all doses at 10 degrees C averaged 62% less than apparent Ka at 15 degrees C. Estimates of the apparent t(1/2)e over both temperatures ranged from 29.5 h (18.4-73.4) to 56.3 h (38.3-106.6). Bioavailability averaged 42% over all doses at 15 degrees C and was decreased to an average of 25% at 10 degrees C. Peak serum concentrations appeared between 6 and 8 h following dosing. A dose of 5 mg/kg/day was estimated to provide average steady-state serum concentrations at 10 degrees C that are approximately 4.5 times the highest reported MIC values for Streptococcus spp., the fish pathogen least sensitive to enrofloxacin. Owing to the long apparent half-life of elimination of enrofloxacin in fingerling trout, it would take approximately 5 to 9 days to achieve these predicted steady-state serum concentrations; this estimate is important when considering the duration of therapy in clinical trials.

Absorption↗

Salmonella typhimurium (TA100) mutagenicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone and its open- and closed-ring analogs.

The mutagenicities of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX, compound 1), 3-chloro-4-(dichloromethyl)-2(5H)-furanone (RMX, compound 6), and 2-(dichloromethyl)-3,3-dichloropropenal (TCB, compound 7) were determined in the same assay and in repetitive determinations using Salmonella typhimurium (TA 100) without microsomal fraction activation. In addition, the mutagenicity of 2-methyl-3,3-dichloropropenal (compound 8) was assayed in the same manner although not simultaneously with MX, RMX, and TCB. This study was undertaken to ascertain the role of open- and closed-ring forms of MX in the mutagenicity of MX. MX proved to be roughly 100 times more mutagenic than the open-ring analogue TCB and 10 times more mutagenic than the closed-ring analogue RMX. Compound 8 was inactive. Assay stability of the three active compounds in Vogel-Bonner medium at 38 degrees C was estimated as the chemical half-life values by following the change in UV absorbance at selected wave lengths. Half-life values were 10.7, 2.6, and 2.8 hr, respectively, for MX, RMX, and TCB. The enhanced mutagenicity of MX relative to RMX and TCB is attributed to the intrinsic mutagenicity of MX and its greater stability is judged to play only a minor role. Moreover, the greater mutagenicity of the closed-ring analogue RMX relative to the open-ring analogue TCB points to the ring form of MX as the active species even though the open form of MX is predominant under assay conditions.

Drug Stability↗

Benzo[e]pyrene pretreatment of immature, female C57BL/6J mice results in increased bioactivation of aflatoxin B1 in vitro.

Hepatic microsomes were prepared from immature C57BL/6J mice 24 h after receiving intraperitoneal injections of either corn oil, benzo[e]pyrene (BeP, 50 mg/kg) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 4 x 10(-3) mg/kg). The capacity of these hepatic microsomes to bioactivate aflatoxin B1 (AFB1), 2-aminoanthracene (AA), benzo[a]pyrene (BaP), 3-methylcholanthrene (MC), 7,12-dimethylbenzanthracene (DMBA), BeP and pyrene (PY) was measured using strain TA100 in the Salmonella typhimurium/microsome reversion assay. BeP pretreatment of mice resulted in a 33% increase in mutagenic potency (MP) of AFB1 over the corn oil controls and a 70% increase in MP relative to TCDD-pretreated microsomes. With AA, BaP and DMBA as promutagens, BeP pretreatment reduced MP an average of 24%, while TCDD pretreatment increased MP of these 3 promutagens 263% compared to controls. Since the general effects of BeP and TCDD on murine hepatic cytochrome P-450 (P450)-mediated activities in this study were discordant, it appears that changes in P450 activity by BeP pretreatment are not mediated through the Ah receptor.

Aflatoxin B1↗

Urinary mutagens in cosmetologists and dental personnel.

Cosmetologists are occupationally exposed to a wide range of toxic chemicals both dermally and by inhalation. Since many of these chemicals are mutagens and may be excreted in urine, the Ames Salmonella typhimurium assay was used to determine the presence of direct-acting and promutagens in the urine of practicing cosmetologists in central New York State. A comparable group (age, gender, smokers) of dental hygienists and assistants in the same geographic area was used as the control cohort. The cosmetologists had a significantly higher (39 vs. 24%, p less than .03) frequency of direct-acting urinary mutagens but there was no difference between the groups in the frequency of promutagens. In the multivariate model, cosmetologists were at two times the risk of direct-acting mutagens compared to dental workers. Smoking regularly, within 24 h of taking the urine sample, and the number of cigarettes smoked daily were not associated significantly with direct-acting mutagens in urine. Similarly, having had a hair permanent or hair dyed within 7 d of urine sampling, years of employment, age, gender and use of protective gear were not predictive of direct-acting urinary mutagens. In contrast, employment was not associated with urinary promutagens but the risk was significantly increased with increasing age and cigarette smoking. Among possible adverse health symptoms queried, only the prevalence of skin rashes differed between the cosmetologists (29%) and dental personnel (15%) (p less than .05).

Adult↗

Pharmacokinetic properties of enrofloxacin in rabbits.

The pharmacokinetic properties of the fluoroquinolone antimicrobial enrofloxacin were studied in New Zealand White rabbits. Four rabbits were each given enrofloxacin as a single 5 mg/kg of body weight dosage by IV, SC, and oral routes over 4 weeks. Serum antimicrobial concentrations were determined for 24 hours after dosing. Compartmental modeling of the IV administration indicated that a 2-compartment open model best described the disposition of enrofloxacin in rabbits. Serum enrofloxacin concentrations after SC and oral dosing were best described by a 1- and 2-compartment model, respectively. Overall elimination half-lives for IV, SC, and oral routes of administration were 2.5, 1.71, and 2.41 hours, respectively. The half-life of absorption for oral dosing was 26 times the half-life of absorption after SC dosing (7.73 hours vs 0.3 hour). The observed time to maximal serum concentration was 0.9 hour after SC dosing and 2.3 hours after oral administration. The observed serum concentrations at these times were 2.07 and 0.452 micrograms/ml, respectively. Mean residence times were 1.55 hours for IV injections, 1.46 hours for SC dosing, and 8.46 hours for oral administration. Enrofloxacin was widely distributed in the rabbit as suggested by the volume of distribution value of 2.12 L/kg calculated from the IV study. The volume of distribution at steady-state was estimated at 0.93 L/kg. Compared with IV administration, bioavailability was 77% after SC dosing and 61% for gastrointestinal absorption. Estimates of predicted average steady-state serum concentrations were 0.359, 0.254, and 0.226 micrograms/ml for IV, SC, and oral administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Urinary mutagens in municipal refuse incinerator workers and water treatment workers.

Municipal refuse incineration workers may be exposed to mutagenic compounds from gaseous and particulate emissions and during ash removal operations. The frequency of urinary mutagens was measured by the Ames test among a sample of 104 refuse incinerator workers in seven incinerator plants during March-May 1988. The frequency was compared to that observed in 61 water treatment employees in 11 municipal water treatment facilities during the same period. Incinerator workers had a significantly higher risk for urinary mutagens and promutagens as compared to water plant workers after controlling for age. Among incinerator workers, increased risk of having urinary mutagens was associated with workers who wore protective clothing (defined as clothing other than masks or gloves) or whose job classification was equipment repair. It also showed a weak positive association with increasing age. There was an increased risk of urinary promutagens associated with not wearing gloves. The presence or absence of mutagenicity in workers' urine varied with plant location. Incinerator operating conditions affecting the production of toxicants and mutagens are discussed and the results of other studies involving toxicant exposure of humans near incinerators are cited.

Adult↗

The fluoroquinolone antimicrobials: structure, antimicrobial activity, pharmacokinetics, clinical use in domestic animals and toxicity.

Fluoroquinolones form a promising family of new bactericidal antimicrobials. Enrofloxacin (Baytril) is the first antibacterial of this family to be available to veterinary medicine. They share a wide spectrum of antimicrobial activity, a large volume of distribution and are active at very low concentrations. Their target site for bactericidal action is the type II topoisomerase (E.C. 5.99.1.3.). The gastrointestinal absorption in mammals is rapid and substantial, the duration of action is long and the excretion mainly through the kidney. Their adverse effects are not severe when compared to the beneficial features fluoroquinolones exhibit. The target tissues for adverse effects are: the juvenile cartilage, central nervous system, urinary tract and digestive tract. In the USA, approved use is thus far limited to dogs; approval for use in food-animals is currently being sought for several fluoroquinolones. Published clinical trials as well as unpublished data from the author's laboratories are reviewed for dogs, cats, pigs, cattle and poultry.

4-Quinolones↗

Toxicity and tissue residue depletion of levamisole hydrochloride in young goats.

Toxicity and tissue residue depletion studies were conducted in young goats, using an oral drench formulation of levamisole hydrochloride. In the target animal toxicity study, 3 groups of 5 goats each were given levamisole orally to provide approximately 11.88, 23.76, or 35.64 mg of levamisole HCl/kg/d for 3 consecutive days; a fourth group of 5 goats served as untreated controls. Blood samples were taken for analysis of levamisole 1 day prior to dosing and 1, 2, 3, 4, and 7 days following the third dose. At the 35.64-mg/kg dose, 2 of 5 goats responded with typical cholinergic signs of toxicosis on each of the 3 days of dosing. The times for the onset of clinical signs of toxicosis ranged from 18 to 63 minutes, with an average duration of 32 minutes. Administration of 23.76 mg of levamisole HCl/kg resulted in hyperactive behavior in 1 of 5 goats only on the first day of dosing; no abnormal behavior was observed in any of the 5 goats following the second or third dose of levamisole HCl at 23.76 mg/kg. Untoward effects were not seen in the 5 goats dosed at 11.88 mg of levamisole HCl/kg or in the controls during the 3-day dosing period or in the following 7-day observation period. Overall, the observed signs of toxicosis did not become more severe, affect more goats, or persist for a longer period on subsequent dosing days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro activation assays with hepatic S9 preparation from wild and laboratory reared woodchucks in the Salmonella mutagenicity test.

The Salmonella mutagenicity assay was utilized to compare hepatic S9 fractions derived from wild and laboratory reared woodchucks (Marmota monax). Two promutagens, 7,12-dimethylbenz[a]anthracence (DMBA) and 2-amino-fluorene (AF) were tested at 5 concentrations with the tester strains TA98 and TA100, against 2 levels of S9 fraction. AF produced similar number of revertants with the S9 fraction from wild and laboratory-reared animals. DMBA produced 2-4 times more revertant colonies at 50 microliter S9/plate with wild woodchuck S9 than with S9 from the laboratory-reared animals with both tester strains. It was concluded that natural inducers in the wild woodchuck diet may have contributed to the increased reversion frequency over laboratory reared woodchucks. Dose-response parameters for the activation of DMBA by S9 fraction from woodchucks and rats were compared with TA100. Woodchuck S9 had 3-40 more revertants/nmol and a 100-fold lower threshold of response than S9 from Aroclor 1254-induced rats.

9,10-Dimethyl-1,2-benzanthracene↗

Health among municipal sewage and water treatment workers.

Municipal sewage treatment plant workers are potentially exposed to a multitude of industrial chemicals and pathogenic microorganisms. A questionnaire survey of working habits, lifestyle and symptoms of illness was conducted among 189 municipal sewage treatment plant workers processing between three and ten million gallons of wastewater daily in 16 plants in New York State between March and July of 1984. Water treatment plant workers in the same cities comprised the comparison group. Sewage workers reported a significantly higher frequency of headache, dizziness, sore throat, skin irritation and diarrhea within the month immediately preceding receipt of the questionnaire, after controlling for various possible confounders. Eye and skin irritation were significantly associated with exposure to mutagens. The health significance of these findings and possible sources of error in assessing risk are discussed.

Humans↗

4-Ipomeanol-induced effects on Sendai viral pneumonia in mice.

The effects of the pulmonary toxicant, 4-ipomeanol (4-IP), on Sendai viral pneumonia was examined in young adult female C57BL/6J mice. The histologic severity of the pneumonia was closely correlated with increasing doses of the compound. The more severe pneumonia observed in the 4-IP-treated animals was associated with higher pulmonary viral titers and a more diffuse distribution of viral antigen in bronchioles and alveolar parenchyma. There was no difference in the systemic humoral immune response against Sendai virus or pulmonary interferon production in animals that had received 4-IP or vehicle pretreatment. Classification of the antigen-positive cell types in the alveolar parenchyma resulted in a marked relative increase in the numbers of antigen-positive macrophages, as compared with other antigen-positive cell types.

Animals↗

H-2 modulation of aryl hydrocarbon hydroxylase induction and the mutagenicity of benzo(a)pyrene after 3-methylcholanthrene treatment.

All strains except the DBA/2J, B10.S and B10.RIII exhibited an increase in hepatic cytochrome P-450 levels following MC treatment; furthermore, the P-450 response of the B10.D2 strains was greater than that seen in the B10 and B6 strains. MC treatment increased BP metabolism in all congenic strains relative to their corn oil controls. Both relative and absolute changes in AHH activity were higher in the B10.D2 than the B6 or B10 reference strains. All congenic strains exhibited an enhanced capacity to produce mutagenic metabolites of BP following treatment with MC; the B10.M, B10.WB and B10.D2 segregated with the B6 and B10 in this regard, while the B10.S and B10.RIII changed least following MC administration.

Animals↗

Noninducibility of cytochrome P-450 in the earthworm Dendrobaena veneta.

Cytochrome P-450 has been measured in the earthworm Dendrobaena veneta (Rosa) in a direct spectrophotometric procedure. The P-450 was found not in the dense microsomal fraction, but in the less dense overlying fraction often referred to as buffy coat. Earthworm P-450 was not induced by 3-methylcholanthrene or phenobarbitol.

Animals↗

Response of Japanese quail fed seed meal from sunflowers grown on a municipal sludge-amended soil: elevation of cadmium in tissues.

Sunflowers were grown on soil amended with 224 metric tons/ha of municipal sewage sludge from Syracuse, N.Y. The yield of sunflower seeds was reduced by 47.2% by the sludge addition. The harvested seeds contained 1.71 ppm dry weight of cadmium. Deoiled seed meal was incorporated as 25 and 50% of semipurified diet and fed to male and female Japanese quail. The concentrations of cadmium were higher in kidney, liver, muscle, and eggs of birds fed the sludge-grown seed meal as compared to control quail. Tissue concentrations of cadmium increased with increasing dietary levels of sludge-grown seed meal. No significant differences (p greater than 0.05) were observed between dietary treatments in the activity of hepatic microsomal p-nitroanisole O-demethylase or aminopyrine N-demethylase in the male birds. Additionally, no mutagenic activity, either direct or with metabolic activation, was found in quail eggs. No observable changes in tissue ultrastructure were observed under electron microscopy in any of the treatment groups. There were no significant (p greater than 0.05) differences among the dietary treatment groups in feed intake, growth rate, egg production, or egg hatchability.

Animals↗

Urinary mutagens in municipal sewage workers and water treatment workers.

In view of the potential exposure of sewage treatment workers to a multitude of mutagenic substances, the frequency of urinary mutagens was measured by the Ames test among a sample of 164 sewage treatment workers employed in 14 sewage treatment plants which processed between 3 and 10 million gallons of sewage daily in New York State between March and July, 1984. The frequency was compared to that observed in 72 water treatment employees in the same municipalities. Sewage workers had a significantly higher risk for urinary mutagens after controlling for smoking, using the Ames test, both with and without the addition of the liver microsomal homogenate, S-9. More precise methods of measuring exposure in epidemiologic studies, particularly in environmental and occupational epidemiology, are in various stages of development. The application of one of these methods, the Ames test, to an occupational group (sewage workers) with potentially high exposure to mutagenic substances is described and the strengths and limitations of this application are discussed.

Adult↗