Dataset Information

Toxicity Evaluation of Exposure to an Atmospheric Mixture of Polychlorinated Biphenyls by Nose-Only and Whole-Body Inhalation Regimens.

ABSTRACT: The health risk of inhalation exposure to polychlorinated biphenyls (PCB) cannot be assessed with high confidence due to the lack of rigorous inhalation studies. One uncertainty rests on exposure regimen, as whole-body exposure systems allow oral PCB intake that confounds the exposure. We conducted contemporaneous PCB inhalation exposures with whole-body and nose-only exposure methods. Female Sprague-Dawley rats were concurrently exposed to vapor-phase PCBs (533 ± 93 ?g/m(3)) generated from PCB11-supplemented Chicago Air Mixture resembling the Chicago airshed, 4 h/day, 6 days/week, for 4 weeks. Congener-specific analysis showed 1.5-fold higher ?PCBs in the lungs of nose-only exposed than the whole-body exposed animals (p = 0.0024). Higher ?PCB concentrations were also found in the sera, livers, brains, and adipose tissue of nose-only exposed animals (1.1-1.5-fold), but these increases were not statistically significant. Congener profiles of five tissue types were dominated by PCB 28/31 and higher-chlorinated congeners in both groups reflecting rapid metabolism of other lower-chlorinated PCBs. No toxicity was seen regarding metabolic enzyme expression, glutathione, or histopathology. However, diminished weight gain and reduced plasma total thyroxine levels were found in both groups compared with controls, after exposure to 76 ?g/m(3) ?PCBs as adjusted for continuous exposure. Hepatic lipid peroxidation was also elevated in the nose-only group. Our study shows that prolonged nose-only exposure was well-tolerated and eliminated the need for housing animals outside the vivarium, thus was preferred for long-term PCB inhalation studies.

SUBMITTER: Hu X

PROVIDER: S-EPMC4711378 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Toxicity Evaluation of Exposure to an Atmospheric Mixture of Polychlorinated Biphenyls by Nose-Only and Whole-Body Inhalation Regimens.

Hu Xin X Adamcakova-Dodd Andrea A Lehmler Hans-Joachim HJ Gibson-Corley Katherine K Thorne Peter S PS

Environmental science & technology 20150922 19

The health risk of inhalation exposure to polychlorinated biphenyls (PCB) cannot be assessed with high confidence due to the lack of rigorous inhalation studies. One uncertainty rests on exposure regimen, as whole-body exposure systems allow oral PCB intake that confounds the exposure. We conducted contemporaneous PCB inhalation exposures with whole-body and nose-only exposure methods. Female Sprague-Dawley rats were concurrently exposed to vapor-phase PCBs (533 ± 93 μg/m(3)) generated from PCB1 ...[more]

PMID: 26348937

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Project description:Hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) have been found to be ubiquitous in the environment due to the oxidative metabolism of their parent PCBs. With more polarity, OH-PCBs may be more toxic and mobile than their parent compounds. However, the behavior and fate of OH-PCBs have been neglected in the environment because they are not the original contaminants. Some of these hydroxylated metabolites are chiral, and chiral compounds can be used to probe biological metabolic processes. Therefore, chiral OH-PCBs were selected to study their uptake, translocation, transformation, and enantioselectivity in plants in this work. Poplars (Populus deltoides × nigra, DN34), a model plant with complete genomic sequence, were hydroponically exposed to 5-hydroxy-2,2',3,4',6-pentachlorobiphenyl (5-OH-PCB91) and 5-hydroxy-2,2',3,5',6-pentachlorobiphenyl (5-OH-PCB95) for 10 days. Chiral 5-OH-PCB91 and 5-OH-PCB95 were clearly shown to be sorbed, taken up, and translocated in whole poplars, and they were detected in various tissues of whole poplars. However, the enantioselectivity of poplar for 5-OH-PCB91 and 5-OH-PCB95 proved to be quite different. The second-eluting enantiomer of OH-PCB95, separated on a chiral column (Phenomenex Lux Cellulose-1), was enantioselectively removed in whole poplar. Enantiomeric fractions in the middle xylem, top bark, top xylem, and stem, reached 0.803 ± 0.022, 0.643 ± 0.110, 0.835 ± 0.087, and 0.830 ± 0.029, respectively. Therefore, 5-OH-PCB95 was significantly enantioselectively biotransformed inside poplar tissues, in contrast to nearly racemic mixtures of 5-OH-PCB95 remaining in hydroponic solutions. Unlike 5-OH-PCB95, 5-OH-PCB91 remained nearly racemic in most tissues of whole poplars during 10 day exposure, suggesting the enantiomers of 5-OH-PCB91 were equally transported and metabolized in whole poplars. This is the first evidence of enantioselectivity of chiral OH-PCBs and suggests that poplars can enantioselectively biotransform at least one chiral OH-PCB: namely, 5-OH-PCB95.

Project description:Propargyl alcohol (PA) is a high production volume chemical used in synthesis of many industrial chemicals and agricultural products. Despite the potential for prolonged or accidental exposure to PA in industrial settings, the toxicity potential of PA was not well characterized. To address the knowledge gaps relevant to the toxicity profile of PA, the National Toxicology Program (NTP) conducted 2-week, 14-week and 2-year studies in male and female F344/N rats and B6C3F1/N mice. For the 2-week inhalation study, the rats and mice were exposed to 0, 31.3, 62.5, 125, 250 or 500ppm. Significant mortality was observed in both rats and mice exposed to ?125ppm of PA. The major target organ of toxicity in both mice and rats was the liver with exposure-related histopathological changes (250 and 500ppm). Based on the decreased survival in the 2-week study, the rats and mice were exposed to 0, 4, 8, 16, 32 or 64ppm of PA in the 14-week study. No treatment-related mortality was observed. Mean body weights of male (?8ppm) and female mice (32 and 64ppm) were significantly decreased (7-16%). Histopathological changes were noted in the nasal cavity, and included suppurative inflammation, squamous metaplasia, hyaline droplet accumulation, olfactory epithelium atrophy, and necrosis. In the 2-year inhalation studies, the rats were exposed to 0, 16, 32 and 64ppm of PA and the mice were exposed to 0, 8, 16 and 32ppm of PA. Survival of male rats was significantly reduced (32 and 64ppm). Mean body weights of 64ppm male rats were significantly decreased relative to the controls. Both mice and rats showed a spectrum of non-neoplastic changes in the nose. Increased neoplastic incidences of nasal respiratory/transitional epithelial adenoma were observed in both rats and mice. The incidence of mononuclear cell leukemia was significantly increased in male rats and was considered to be treatment-related. In conclusion, the key findings from this study indicated that the nose was the primary target organ of toxicity for PA. Long term inhalation exposure to PA led to nonneoplastic changes in the nose, and increased incidences of respiratory/transitional epithelial adenomas in both mice and rats. Increased incidences of harderian gland adenoma may also have been related to exposure to PA in male mice.

Dataset Information

Toxicity Evaluation of Exposure to an Atmospheric Mixture of Polychlorinated Biphenyls by Nose-Only and Whole-Body Inhalation Regimens.

Publications

Toxicity Evaluation of Exposure to an Atmospheric Mixture of Polychlorinated Biphenyls by Nose-Only and Whole-Body Inhalation Regimens.

Similar Datasets

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