Abstract  OBJECTIVE: To establish a method for determination 1-bromopropane (1-BP) in workplace air by gas chromatography-flame ionization detector (GC-FID).

METHOD: 1-bromopropane in workplace air was collected with activated charcoal tube, then desorbed by carbon disulfide and determined by GC-FID. 1-bromopropane was quantitatively measured using retention time and peak area.

RESULTS: Linear regression formula was Y = 3353.4x-10064 in a range of 2.50 ∼ 500.00 µg/ml with regression coefficient R = 0.9998. Detection limit was 0.25 µg/ml and the lowest detection concentration of 1-brmopropane in air was 0.14 mg/m(3) (at air volume 1.8L). The mean recoveries of 1-BP were between 96.8% and 102.6%, and relative standard deviation of inter and intra-assay was less than 10%. The average desorption efficiencies were between 93.2% and 104.4%. The samples in activated charcoal tube could be stably stored for 5 days at room temperature.

CONCLUSION: The method could be feasible to determine 1-bromopropane in workplace air.

Abstract  1-Bromopropane (1-BP), an alternative to ozone-depleting solvents (ODS), exhibits central nervous system (CNS) toxicity in animals and humans. This study was designed to relate CNS damage by Morris water maze (MWM) test and oxidative stress to 1-BP exposure in the rat. Male Wistar rats were randomly divided into 4 groups (n=10), and treated with 0, 200, 400 and 800 mg/kgbw 1-BP for consecutive 12 days, respectively. From day 8 to day 12 of the experiment, MWM test was employed to assess the cognitive function of rats. The cerebral cortex of rats was obtained immediately following the 24h after MWM test conclusion. Glutathione (GSH), oxidized glutathione (GSSG) and total thiol (total-SH) content, GSH reductase (GR) and GSH peroxidase (GSH-Px) activities, malondialdehyde (MDA) level, as well as 4-hydroxynonenal (4-HNE) and MDA modified proteins in homogenates of cerebral cortex were measured. The obtained results showed that 1-BP led to cognitive dysfunction of rats, which was evidenced by delayed escape latency time and swimming distances in MWM performance. GSH and total-SH content, GSH/GSSG ratio, GR activity significantly decreased in cerebral cortex of rats, coupling with the increase of MDA level. 4-HNE and MDA modified protein levels obviously elevated after 1-BP exposure. GSH-Px activities in cerebral cortex of rats also increased. These data suggested that 1-BP resulted in enhanced lipid peroxidation of brain, which might play an important role in CNS damage induced by 1-BP.

Abstract  Chronic inhalation of 1-bromopropane (1-BP), a substitute of ozone-depleting chlorofluorocarbons, has been suspected of having central neurotoxicity (Clinical Neurology and Neurosurgery 101 (1999) 199; Journal of Occupational Health 44 (2002) 1) for humans. In animal experiments, 1-BP inhalation (1500 ppm) caused hyperexcitability in the CA1 and the dentate gyrus (DG) [Journal of Occupational Health 42 (2000) 149, Journal of Occupational Health 44 (2002) 156]. We studied whether the hyperexcitability is associated with changes of Ca2+/calmodulin-dependent kinase II (CaMKII), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Male Wistar rats were exposed to 1-BP for 6 hours in a day in an exposure chamber with a concentration of 700 ppm for 8 weeks. After the inhalation, paired-pulse ratios of field excitatory postsynaptic potentials and population spikes (PSs) were analyzed in the CA1 and DG of hippocampal slices. Control rats were then given fresh air in the inhalation chamber. Semiquantitative immunoblotting analyses of protein kinases using antibodies against active and conventional protein kinases were done using the whole hippocampus. A paired-pulse ratio of PS was increased at the 5 ms interpulse interval in the CA1 and at the 10-20 ms interpulse intervals in the DG. The amount of active MAPK and total amount of CaMKIIalpha and beta were significantly increased by 28, 29, and 46% compared to control, respectively, without any change in PKC activity. In contrast, the amount of active CaMKIIbeta was decreased to 78%. These results suggest that modifications of intracellular signaling cascades are associated with hyperexcitability that occurred in the hippocampal formation of rats exposed to the chronic inhalation of 1-BP.

Abstract  Wistar male rats were exposed to 1-bromopromane (1-BP) vapor for 6 h a day, 5 days a week, for 3 and 4 weeks (1500 ppm) and 1 day, and 4 and 12 weeks (700 ppm). After the exposures, 1-BP and its metabolites were measured temporally. In the samples obtained from the 700 ppm exposures, hematological and biochemical examinations in blood and measurements of hepatic cytochromes P450 were carried out. 1-BP in blood decreased rapidly to the detection limit within 0.7 h. On the other hand, bromine ion persisted longer in both blood and urine; the biological half-life of bromine ion was 4.7-15.0 days in blood and 5.0-7.5 days in urine. Glycidol was detected in the urine samples. Based on the experimental results, the metabolic pathway of 1-BP was discussed. Hepatic cytochromes P450, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in blood decreased significantly with 1-BP exposure, but other enzyme activities did not differ significantly.

Abstract  1. The metabolism of 1-bromopropane in the rat has been re-investigated. The previously known metabolites have been isolated and confirmed as the three mercapturic acids N-acetyl-S-propyl cysteine, N-acetyl-S-propyl cysteine-S-oxide and N-acetyl-S-(2-hydroxypropyl)cysteine. 2. Three further metabolites have been isolated from the urine of rats treated with 4-bromopropane. These have been identified as 3-bromopropionic acid and the mercapturic acids N-acetyl-S-(3-hydroxypropyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine. 3. The metabolites of 3-bromopropanol and 3-chloropropanol in the rat have been shown to be the mercapturic acids N-acetyl-S-(3-hydroxypropyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine and the corresponding 2-carboxyethyl halide. 4. Studies with 1-bromopropane and the 3-halopropanols in vitro indicate that oxidation of C3 and C2 of 1-bromopropane occurs before conjugation of the alkyl group with glutathione. The implications of these studies are discussed in relation to the mechanism of the biosynthesis of the S-(2-hydroxyalkyl)mercapturic acid metabolites derived from the alkyl halides.

Abstract  The purposes of the present study are (1) to develop a sensitive analytical method to measure 1-bromopropane (1-BP) in urine, (2) to examine if 1-BP or bromide ion (Br) in urine is a useful biomarker of exposure to 1-BP, and (3) to identify the lowest 1-BP exposure concentration the method thus established can biomonitor. A factory survey was carried out on Friday, and 33 workers (all men) in cleaning and painting workshops participated; each worker was equipped with a diffusive sampler (carbon cloth KF-1500 as an adsorbent) to monitor 1-BP vapour for an 8-h shift, and offered a urine sample at the end of the shift for measurement of 1-BP and Br in urine. In addition, 10 non-exposed men offered urine samples as controls. The performance of the carbon cloth diffusive sampler was examined to confirm that the sampler is suitable for monitoring time-weighted average 1-BP vapour exposure. A head-space GC technique was employed for analysis of 1-BP in urine, whereas Br in urine was analysed by ECD-GC after derivatization to methyl bromide. The workers were exposed to vapours of seven other solvents (i.e. toluene, xylenes, ethylbenzene, acetone, etc.) in addition to 1-BP vapour; the 1-BP vapour concentration was 1.4 ppm as GM and 28 ppm as the maximum. Multiple regression analysis however showed that 1-BP was the only variable that influenced urinary 1-BP significantly. There was a close correlation between 1-BP in urine and 1-BP in air; the correlation coefficient (r) was >0.9 with a narrow variation range, and the regression line passed very close to the origin so that 2 ppm 1-BP exposure can be readily biomonitored. The correlation of Br in urine with 1-BP in air was also significant, but the r (about 0.7) was smaller than that for 1-BP, and the background Br level was also substantial (about 8 mg l-1). Thus, it was concluded that 1-BP in end-of-shift urine is a reliable biomarker of occupational exposure to 1-BP vapour, and that Br in urine is less reliable.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM NOTE RESEARCH ARTICLE WISTAR RAT MALE FEMALE 1-BROMOPROPANE TOXICOKINETICS TOXICITY HEPATIC METABOLISM PARTITION COEFFICIENT ANEMIA AMENORRHEA OLIGOSPERMIA HEPATIC MICROSOMES 2-BROMOPROPANE TOXICOLOGY BLOOD AND LYMPHATIC DISEASE REPRODUCTIVE SYSTEM DISEASE-FEMALE REPRODUCTIVE SYSTEM DISEASE-MALE KOREA PALEARCTIC REGION

Abstract  To investigate the effects on the central nervous system of subchronic exposure to 1-bromopropane (1-BP), which is a substitute for chlorofluorocarbons, we measured the hippocampal excitability of 1-BP-treated rats electrophysiologically. Male Wistar rats were exposed to 1-BP for 6-h in a day in an exposure chamber (1,500 ppm) for 4 wk. After the 1-, 3- and 4-wk inhalation, field excitatory postsynaptic potentials (fEPSPs), population spikes (PSs), fEPSP/spike (E/S) curve, paired-pulse profiles of fEPSP slopes and PS amplitudes recorded from CA1 pyramidal neurons, and dentate granule cells of the hippocampal slice obtained from the rats were analyzed. In 1-BP treated rats, E/S potentiation and a lower subthreshold of PSs were observed in the dentate gyrus (DG) after the 3 and 4-wk inhalation. Paired-pulse inhibition was reduced at 5-50 ms in the CA1 and at 5-20 ms in the DG after all of the inhalation. These changes were not associated with paired-pulse inhibition of fEPSPs. In the DG, the paired-pulse inhibition at the short interpulse intervals in rats exposed to 1-BP was pronounced by an application of A type gamma aminobutyric acid (GABA) receptor agonist pentobarbital. Impaired paired-pulse inhibition of granule cells at the short interpulse intervals was recovered after the application of N-methyl-D-aspartate (NMDA) type glutamate receptor antagonist DL-2-amino-5-phosphonopentanoic acid. Convulsing rats observed after the 4-wk inhalation exhibited multiple PSs in the DG, and their second component was abolished by an application of this antagonist. Inhalation of 1-BP increased the neuronal excitability in the hippocampal CA1 and the DG. The hyperexcitability of the granule cells in the DG was at least due to an over-activation of NMDA receptors.

Abstract  Ethylene oxide (EO) and propylene oxide (PO) are direct acting mutagens with high Swain-Scott s-values, which indicate that they react preferentially with ring nitrogens in the DNA. We have previously described that in the X-linked recessive lethal (RL) assay in Drosophila postmeiotic male germ cells EO is, per unit exposure dose, 5-10 times more mutagenic than PO. Furthermore, at the higher dose range of EO tested, 62.5-1000 ppm, up to 20-fold enhanced mutation rates were measured in the absence of maternal nucleotide excision repair (NER) compared to repair proficient conditions. The lower dose range of EO tested, 2-7.8 ppm, still produced a small increased mutation rate but without a significant elevated effect when the NER system is being suppressed. The lowest dose of PO tested, 15.6 ppm, produced only in NER- condition an increased mutation rate. The aim of the present study was to compare the mutagenic effect of EO and PO in the RL assay under XPG proficient and deficient conditions with the formation of N-7-(2-hydroxyethyl)guanine (7-HEG) and N-7-(2-hydroxypropyl)guanine (7-HPG), respectively, the major DNA adducts formed. The formation of 7-HEG and 7-HPG was investigated in Drosophila males exposed to EO and PO as a measure of internal dose for exposures ranging from 2 to 1000 or 2000 ppm, respectively, for 24h. Analysis of 7-HEG and 7-HPG, using a highly sensitive 32P-postlabelling assay, showed a linear increase of adduct levels over the entire dose range. The non-linear dose-response relationship for mutations could therefore not be explained by a reduced inhalation or increased detoxification at higher exposure levels. In analogy with the four times higher reactivity of EO the level of N-7-guanine alkylation per ppm was for EO 3.5-fold higher than that for PO. Per unit N-7-guanine alkylation EO was found to be slightly more mutagenic than PO, whereas PO was the more potent clastogenic agent. While this research has not identified the DNA lesions that cause the increase in repair deficient flies, it supports the hypothesis that efficient error-free repair of some N-alkylation products can explain why these agents tend to be weakly genotoxic or even inactive in repair-competent (premeiotic) germ cells of the mouse and the Drosophila fly.

Abstract  1-Bromopropane (1-BP) has been marketed as an alternative for ozone depleting solvents and suspect carcinogens and is in aerosol products, adhesives and solvents used for metal, precision and electronics cleaning. Toxicity of 1-BP is poorly understood, but it may be a neurologic, reproductive and hematologic toxin. Sparse exposure information prompted this exposure assessment study using air sampling, and measurement of urinary metabolites. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving removal of bromide (Br) from the propyl group. One research objective was to evaluate the utility of urinary Br analysis for assessing 1-BP exposure using a relatively inexpensive, commercially available method. Complete 48 h urine specimens were obtained from 30 workers on two consecutive days at two facilities using 1-BP adhesives to construct polyurethane foam seat cushions and from seven unexposed control subjects. All of the workers' urine was collected into composite samples representing three daily time intervals (at work; after work but before bedtime; and upon wake-up) and analyzed for Br ion by inductively coupled plasma-mass spectrometry. Full-shift breathing zone samples were collected for 1-BP on Anasorb carbon molecular sieve sorbent tubes and analyzed by gas chromatography-flame ionization detection via NIOSH method 1025. Geometric mean (GM) breathing zone concentrations of 1-BP were 92 parts per million (p.p.m.) for adhesive sprayers and 11 p.p.m. for other jobs. For sprayers, urinary Br concentrations ranged from 77 to 542 milligrams per gram of creatinine [mg (g-cr)^-1] at work; from 58 to 308 mg (g-cr)^-1 after work; and from 46 to 672 mg (g-cr)^-1 in wake-up samples. Pre-week urinary Br concentrations for sprayers were substantially higher than for the non-sprayers and controls, with GMs of 102, 31 and 3.8 mg (g-cr)^-1, respectively. An association of 48 h urinary Br concentration with 1-BP exposure was statistically significant (r² = 0.89) for all jobs combined. This study demonstrates that urinary elimination is an important excretion pathway for 1-BP metabolism, and Br may be a useful biomarker of exposure.

Abstract  Bromodichloromethane (99% pure), one of several trihalomethanes commonly formed after chlorination of water, was selected for study because no carcinogenicity data were available for this compound and because chloroform, a related trihalomethane, had been found to cause tumors in rodents. The general population might be exposed to bromodichloromethane in drinking water supplies, in swimming pools, and in a variety of food substances. Single-administration, 14-day, 13-week, and 2-year studies were conducted in F344/N rats and B6C3F1 mice. The chemical was administered by gavage in corn oil because human exposure is primarily oral. Additional studies were performed to evaluate the potential for genetic damage in bacteria and mammalian cells. Results of the short-term studies In the single-administration studies, the chemical was administered at doses of 150-2,500 mg/kg per day. All rats and female mice at 1,250 and 2,500 mg/kg and all male mice at 600, 1,250, and 2,500 mg/kg died; 2/5 male rats, 1/5 female rats, and 2/5 female mice at 600 mg/kg died; all animals at lower dose levels survived. In the 14-day studies, rats received doses of 38-600 mg/kg, and mice received doses of 19-300 mg/kg per day. One female rat at 38 mg/kg and one female rat at 600 mg/kg died. Weight loss or decreased weight gain was seen at 300 and 600 mg/kg in male and female rats. All male mice at 150 and 300 mg/kg died, and one female mouse at 300 mg/kg died; no weight effects were observed in surviving mice. Dose-related necropsy findings included reddened renal medullae in male rats at 600 mg/kg and in male mice at 150 and 300 mg/kg. Clinical signs seen in high dose groups after dosing were hyperactivity in rats and lethargy in mice. In the 13-week studies, male and female rats received doses of 19-300 mg/kg per day, male mice received doses of 6.25-100 mg/kg per day, and female mice received doses of 25-400 mg/kg per day. Five of 10 male rats and 2/10 female rats at 300 mg/kg died. None of the mice died. Final body weights of male and female rats at 150 and 300 mg/kg were lower than those of vehicle controls (45%-88% of vehicle control weights); final body weights of male mice at 100 mg/kg and female mice at 400 mg/kg were 92% and 94% of those of the vehicle controls. Centrilobular degeneration in the liver and degeneration and necrosis of the kidney were seen in male rats at 300 mg/kg; centrilobular degeneration was seen in female rats at 300 mg/kg; degeneration andnecrosis of the kidney were seen in male mice at 100 mg/kg, and centrilobular degeneration of the liver was seen in female mice at 200 and 400 mg/kg. Two-year studies Survival and body weight Final survival of dosed rats was comparable to that of vehicle controls (male: vehicle control, 28/50; low dose, 36/50; high dose, 28/50; female: 34/50; 27/50; 41/50). Mean body weights of high dose male and female rats were decreased during the last 1.5 years of the study; final mean body weights of high dose male and female rats were 88% and 79% of the vehicle control mean weights. Final mean body weights of low dose male and female rats were comparable to those of the vehicle controls. Final survival of dosed male mice was comparable to that of the vehicle controls (34/50; 32/50; 42/50). At week 84, survival of female mice was greater than 50% in all dose groups. After week 84, survival of dosed and vehicle control female mice was reduced (final survival: 26/50; 13/50; 15/50), and this decreased survival was associated with ovarian abscesses (8/50; 19/47; 18/49). The final mean body weight of high dose male mice was 95% that of the vehicle controls; the final mean body weight of low dose male mice was comparable to that of the vehicle controls. Mean body weights of the high dose female mice were decreased during the last 1.5 years of the study; the final mean body weight was 75% that of the vehicle controls. The final mean body weight of the low dose female mice was 91% that of the vehicle controls. Nonneoplastic effects Compound-related nonneoplastic lesions included cytomegaly and tubular cell hyperplasia of the kidney and necrosis and fatty metamorphosis of the liver in male rats; eosinophilic cytoplasmic change, clear cell change, focal cellular change, and fatty metamorphosis of the liver and tubular cell hyperplasia of the kidney in female rats; fatty metamorphosisof the liver, renal cytomegaly, and follicular cell hyperplasia of the thyroid gland in male mice; and follicular cell hyperplasia of the thyroid gland in female mice. Neoplastic effects Bromodichloromethane caused compound-related increases in the incidences of neoplasms of the large intestine and kidney in male and female rats, the kidney in male mice, and the liver in female mice, as shown in the table (see page 5 of the Technical Report). The neoplasms of the large intestine and kidney are uncommon tumors in F344/N rats and B6C3F1 mice. Administration of bromodichloromethane was also associated with a decrease in the tumors of the adrenal glands in male rats, the pituitary and mammary glands in female rats, and the pituitary gland in female mice. Data audit An audit of the experimental data was conducted for the 2-year toxicology and carcinogenesis studies of bromodichloromethane. No discrepancies were found that influenced the final interpretations of the results of these studies. Conclusions Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity for male and female F344/N rats and B6C3F1 mice as shown by increased incidences of tubular cell adenomas and adenocarcinomas in the kidney and adenocarcinomas and adenomatous polyps in the large intestine in male and female rats, increased incidences of tubular cell adenomas and adenocarcinomas in the kidney of male mice, and increased incidences of hepatocellular adenomas and carcinomas in female mice.

Abstract  Two mononuclear Cu(I) complexes based on 2-(2-pyridyl)benzimidazolyl derivative ligand containing electron-transporting 1,3,4-oxadiazole group (L), [Cu(L)(PPh(3))2](BF(4)) and [Cu(L)(DPEphos)](BF(4)), where L = 1-(4-(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)benzyl)-2-(pyridin-2-yl)benzimidazole and DPEphos = bis[2-(diphenylphosphino)phenyl]ether, have been successfully synthesized and characterized. The X-ray crystal structure analyses of the ligand L and the complex [Cu(L)(PPh(3))2](BF(4)) were described. The photophysical properties of the complexes were examined by using UV-vis, photoluminescence spectroscopic analysis. The doped light-emitting devices using the Cu(I) complexes as dopants were fabricated. With no electron transporting layers employed in the devices, yellow electroluminescence from Cu(I) complexes were observed. The devices based on the complex [Cu(L)(DPEphos)](BF4) possess better performance as compared with the devices fabricated by the complex [Cu(L)(PPh(3))2](BF(4)). The devices with the structure of ITO/MoO(3) (2 nm)/NPB (40 nm)/CBP:[Cu(L)(DPEphos)](BF(4)) (8 wt%, 30 nm)/BCP (30 nm)/LiF (1 nm)/Al (150 nm) exhibit a maximum efficiency of 3.04 cd/A and a maximum brightness of 4,758 cd/m(2).

Abstract  1-Bromopropane (1-BP) is widely used in spray adhesives, precision cleaner, and degreaser. This study was conducted to investigate the potential of 1-BP to induce dominant lethality in mice. 1-BP was orally administered to males at doses of 300 and 600 mg/kg for 10 days before mating. Cyclophosphamide was used as a positive control (PC), which was administered intraperitoneally to males at 40 mg/kg for 5 days. The vehicle control (VC) group received corn oil only. Thereafter, males were mated with untreated females during six sequential mating periods of a week each. Males were sacrificed at the end of mating and so were the pregnant females on days 15-17 of gestation. Clinical signs, gross findings, mating index, gestation index, the numbers of corpora lutea, implantations, live fetuses, resorptions and dead fetuses, pre- and post-implantation losses, and dominant lethal mutation rate were examined. There were no treatment-related changes in clinical signs, gross findings, mating index, gestation index, number of corpora lutea and implantations, pre-implantation loss, live fetuses, resorptions, dead fetuses, post-implantation loss at any 1-BP doses tested. In the PC group, there were no treatment-related changes in mating index, gestation index, number of corpora lutea, and dead fetuses. However, a decrease in the number of implantations and an increase in pre-implantation loss were observed during the first 2 weeks as compared to those of the VC group. No treatment-related changes were observed in the third to sixth weeks. Increases in resorptions, fetal deaths and post-implantation loss, and a decrease in the number of live fetuses were observed in the first 3 weeks of the PC group compared to those of the VC group. However, no treatment-related changes were observed during the forth to sixth weeks. An increase in dominant lethal mutation rate was observed in 1-3 weeks of mating of the PC group, but there was no significant difference in 1-6 weeks of mating of the 1-BP treatment groups. In conclusion, 1-BP did not induce dominant lethality in mice. These results are in agreement with the report of Saito-Suzuki et al., demonstrating that no dominant lethality of 1-BP was observed in Sprague-Dawley rats.

Abstract  The in vitro metabolism of 1-propyl halides (chloride, bromide, and iodide) by hepatic microsomes from phenobarbital-induced rats was examined. The following metabolites were detected: propene, 1,2-epoxypropane, 1,2-propanediol, propionic acid, and undefined species bound to protein (for propyl chloride). The addition of exogenous glutathione to the incubation mixture led to the production of S-(1'-propyl)glutathione and S-(2'-hydroxy-1'-propyl)glutathione. The ratio of the metabolites resulting from C1-C2 functionalization [propene, 1,2-propanediol, and S-(2'-hydroxy-1'-propyl)glutathione] to that resulting from C1 functionalization (propionic acid) increased as the halide progressed down the halide order chloride bromide, and iodide. Mechanisms which rationalize the distribution of propyl halide metabolites as a function of the halide are discussed. The preferred mechanism interprets that the results obtained are a consequence of the partitioning of the initial metabolic transformation between alpha-hydroxylation and halogen oxygenation pathways.

Abstract  Many states are considering, and some states have actively pursued, banning the use of perchloroethylene (PERC) in dry cleaning establishments. Proposed legislation has led many dry cleaners to consider the use of products that contain greater than 90% n-propyl bromide (n-PB; also called 1-bromopropane or 1-BP). Very little information is known about toxicity and exposure to n-PB. Some n-PB-containing products are marketed as nonhazardous and "green" or "organic." This has resulted in some users perceiving the solvent as nontoxic and has resulted in at least one significant poisoning incident in New Jersey. In addition, many dry cleaning operators may not realize that the machine components and settings must be changed when converting from PERC to n-PB containing products. Not performing these modifications may result in overheating and significant leaks in the dry cleaning equipment. A preliminary investigation was conducted of the potential exposures to n-PB and isopropyl bromide (iso-PB; also called 2-bromopropane or 2-BP) among dry cleaners in New Jersey who have converted their machines from PERC to these new solvent products. Personal breathing zone and area samples were collected using the National Institute for Occupational Safety and Health Sampling and Analytical Method 1025, with a slight modification to gas chromatography conditions to facilitate better separation of n-PB from iso-PB. During the preliminary investigation, exposures to n-PB among some workers in two of three shops were measured that were greater than the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) for n-PB. The highest exposure measured among a dry cleaning machine operator was 54 parts per million (ppm) as an 8-hr time-weighted average, which is more than 5 times the ACGIH TLV of 10 ppm. The preliminary investigation also found that the work tasks most likely to result in the highest short-term exposures included the introduction of solvent to the machine, maintenance of the machine, unloading and handling of recently cleaned clothes, and interrupting the wash cycle of the machine. In addition, this assessment suggested that leaks may have contributed to exposure and may have resulted from normal machine wear over time, ineffective maintenance, and from the incompatibility of n-PB with gasket materials.

Abstract  nfxB encodes a negative regulator of the mexCD-oprJ genes for drug efflux in the opportunistic pathogen Pseudomonas aeruginosa. Inactivating mutations in this transcriptional regulator constitute one of the main mechanisms of resistance to ciprofloxacin (Cip(r)). In this work, we evaluated the use of nfxB/Cip(r) as a new test system to study mutation spectra in P. aeruginosa. The analysis of 240 mutations in nfxB occurring spontaneously in the wild-type and mutator backgrounds or induced by mutagens showed that nfxB/Cip(r) offers several advantages compared with other mutation detection systems. Identification of nfxB mutations was easy since the entire open reading frame and its promoter region were sequenced from the chromosome using a single primer. Mutations detected in nfxB included all transitions and transversions, 1-bp deletions and insertions, >1-bp deletions and duplications. The broad mutation spectrum observed in nfxB relies on the selection of loss-of-function changes, as we confirmed by generating a structural model of the NfxB repressor and evaluating the significance of each detected mutation. The mutation spectra characterized in the mutS, mutT, mutY and mutM mutator backgrounds or induced by the mutagenic agents 2-aminopurine, cisplatin and hydrogen peroxide were in agreement with their predicted mutational specificities. Additionally, this system allowed the analysis of sequence context effects since point mutations occurred at 85 different sites distributed over the entire nfxB. Significant hotspots and preferred sequence contexts were observed for spontaneous and mutagen-induced mutation spectra. Finally, we demonstrated the utility of a luminescence-based reporter for identification of nfxB mutants previous to sequencing analysis. Thus, the nfxB/Cip(r) system in combination with the luminescent reporter may be a valuable tool for studying mutational processes in Pseudomonas spp. wherein the genes encoding the NfxB repressor and the associated efflux pump are conserved.

Abstract  Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after α-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor β1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy.

Abstract  In the Upper Valley of Río Negro and Río Neuquén in Argentina, agriculture represents the second most important economic activity. Azinphos-methyl has been found in water from this region throughout the year at a maximum concentration of 22.48 μg L(-1) during the application period. Toxicological studies on local non-target species have been performed mostly on vertebrates, while mollusks, which could be more sensitive, have not been studied so far. This work aims to characterize cholinesterase (ChE) and carboxilesterase (CE) activities of Chilina gibbosa, a freshwater gastropod native to southern Argentina and Chile. These enzymes, together with neurotoxicity signals, are evaluated herein after as sensitive biomarkers of exposure to azinphos-methyl at environmentally relevant concentrations. Effects of azinphos-methyl on antioxidant defenses: glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase (GST) are also studied in order to complete a set of biomarkers with different sensitivity and specificity, to propose C. gibbosa as a sentinel species. The highest specific activity was obtained with acetylthiocholine as substrate, followed by propionylthiocholine (83% in comparison to acetylthiocholine) and butyrylthiocholine (19%).The lowest Km and the highest efficiency for ChE were obtained with acetylthiocholine. Regarding CEs activities, a higher efficiency was obtained with p-nitrophenyl butyrate than with p-nitrophenyl acetate. Eserine produced significant inhibition of ChE activity (81% with 0.001 mM and 98% with 1mM) while iso-OMPA did not produce any significant effect on ChE. Our results show that C. gibbosa ChE is very sensitive to azinphos-methyl (CI50 0.02 μg L(-1)) while CEs are inhibited at higher concentrations (CI50 1,000 μg L(-1)). CEs have been reported to be more sensitive to OPs than ChEs in most of the aquatic invertebrates protecting the organisms from neurotoxic effects. In contrast, C. gibbosa, has ChE which are much more sensitive to azinphos-methyl than CEs and shows marked signs of neurotoxicity. Regarding antioxidant defenses, GSH levels were significantly increased by 0.02 and 20 μg L(-1) azinphos-methyl (80 and 103%, respectively), CAT activity was increased 85% only at 0.02 μg L(-1) and SOD and GST did not show any significant response. Since ChE activity, neurotoxicity signs, GSH and CAT are sensitive biomarkers of acute exposure to azinphos-methyl at environmental concentrations C. gibbosa could be included as sentinel species in monitoring programs of pesticide hazard in regions of Argentina and Chile.

Abstract  1-Bromopropane (1-BP) has been marketed as an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, metal, precision, and electronics cleaning solvents. Mechanisms of toxicity of 1-BP are not fully understood, but it may be a neurological and reproductive toxicant. Sparse exposure information prompted this study using 1-BP air sampling and urinary metabolites. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. Research objectives were to evaluate the utility of urinary N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) for assessing exposure to 1-BP and compare it to urinary bromide [Br((-))] previously reported for these workers. Forty-eight-hour urine specimens were obtained from 30 workers at two factories where 1-BP spray adhesives were used to construct polyurethane foam seat cushions. Urine specimens were also obtained from 21 unexposed control subjects. All the workers' urine was collected into composite samples representing three time intervals: at work, after work but before bedtime, and upon awakening. Time-weighted average (TWA) geometric mean breathing zone concentrations were 92.4 and 10.5 p.p.m. for spraying and non-spraying jobs, respectively. Urinary AcPrCys showed the same trend as TWA exposures to 1-BP: higher levels were observed for sprayers. Associations of AcPrCys concentrations, adjusted for creatinine, with 1-BP TWA exposure were statistically significant for both sprayers (P < 0.05) and non-sprayers (P < 0.01). Spearman correlation coefficients for AcPrCys and Br((-)) analyses determined from the same urine specimens were highly correlated (P < 0.0001). This study confirms that urinary AcPrCys is an important 1-BP metabolite and an effective biomarker for highly exposed foam cushion workers.

Abstract  While scientific knowledge of the potential health significance of chemical exposures has grown, experimental methods for predicting the carcinogenicity of environmental agents have not been substantially updated in the last two decades. Current methodologies focus first on identifying genotoxicants under the premise that agents capable of directly damaging DNA are most likely to be carcinogenic to humans. Emphasis on the distinction between genotoxic and non-genotoxic carcinogens is also motivated by assumed implications for the dose-response curve; it is purported that genotoxicants would lack a threshold in the low dose region, in contrast to non-genotoxic agents. However, for the vast majority of carcinogens, little if any empirical data exist to clarify the nature of the cancer dose-response relationship at low doses in the exposed human population. Recent advances in scientific understanding of cancer biology-and increased appreciation of the multiple impacts of carcinogens on this disease process-support the view that environmental chemicals can act through multiple toxicity pathways, modes and/or mechanisms of action to induce cancer and other adverse health outcomes. Moreover, the relationship between dose and a particular outcome in an individual could take multiple forms depending on genetic background, target tissue, internal dose and other factors besides mechanisms or modes of action: inter-individual variability and susceptibility in response are, in turn, key determinants of the population dose-response curve. New bioanalytical approaches (e.g., transcriptomics, proteomics, and metabolomics) applied in human, animal and in vitro studies could better characterize a wider array of hazard traits and improve the ability to predict the potential carcinogenicity of chemicals. Published by Elsevier B.V

Abstract  We have designed a closed, inert incubation system for testing the mutagenicity of volatile compounds. The containment properties of this system have been investigated using carbon-14 labelled 1,2-dibromoethane. The recovery of this solvent was about 95% following a 48-h incubation at 37 degrees. Using the Ames Salmonella/microsome mutagenicity assay we have determined the mutagenic potency of 10 common halogenated alkane solvents. Of these 10 compounds, only 1,2-dibromoethane and 1-bromo-2-chloroethane give positive results in the standard test procedure, whereas 7 of the 10 give positive results in the closed system. The specificity observed for reversion of the tester strains and the lack of any significant effect of added rat-liver "S9" fractions suggest that these haloalkanes are direct-acting "base-pair" type mutagens. The mutagenic potencies of the 7 positive compounds range from 0.001 revertants per nanomole for 1,2-dichloroethane to 0.172 revertants per nanomole for 1,2-dibromoethane. A minimum or threshold response level for each material has been calculated