| 1. |
- Koch, Bo L., et al.
(författare)
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Inhalation of substance P and thiorphan : acute toxicity and effects on respiration in conscious guinea pigs.
- 1999
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Ingår i: Journal of Applied Toxicology. - 0260-437X .- 1099-1263. ; 19:1, s. 19-23
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Tidskriftsartikel (refereegranskat)abstract
- Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.
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| 2. |
- Andersson, Lena, et al.
(författare)
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Methodological aspects on measurement of Clara cell protein in urine as a biomarker for airway toxicity, compared with serum levels.
- 2007
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Ingår i: Journal of applied toxicology : JAT. - : Wiley. - 0260-437X .- 1099-1263. ; 27:1, s. 60-6
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Tidskriftsartikel (refereegranskat)abstract
- The Clara cell protein CC16, secreted from Clara cells in the lung, is discussed as a potential biomarker for toxic effects on the airways. An increased concentration of CC16 in serum may be caused by increased permeability of the lungs, caused by high levels of air pollution. Since CC16 is eliminated by renal excretion, it may be possible to use urine instead of serum samples. Few studies have been conducted on urinary CC16 (U-CC16), however.The aim was to investigate the optimal way of sampling and quantifying CC16 in urine samples and compare CC16 in human serum and urinary samples. Repeated sampling was performed in two groups of healthy subjects. First morning urine, 24 h urine, and matched blood and urine samples were collected.The excretion of U-CC16 increased over the day, e.g. from 0.08 microg h(-1) in the morning to 0.28 microg h(-1) in daytime and 0.16 microg h(-1) in the evening (medians in males). Morning samples (microg h(-1)) from males properly reflected the 24 h excretion (r = 0.91). The best correlation with 24 h excretion was obtained with creatinine-corrected first morning urine samples (r > 0.9). Generally, females had lower excretion of CC16 than males (medians 2.5 microg 24 h(-1) in females and 16 microg 24 h(-1) in males). There was significant intraindividual variation, but the interindividual variation was larger in both groups. There was an association between serum CC16 (S-CC16) and U-CC16 in morning samples. With optimal methods for sampling U-CC16, urine samples may be used in experimental studies of air pollution.
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| 5. |
- Beronius, Anna, et al.
(författare)
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Facilitating the use of non-standard in vivo studies in health risk assessment of chemicals : a proposal to improve evaluation criteria and reporting
- 2014
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Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 34:6, s. 607-617
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Tidskriftsartikel (refereegranskat)abstract
- To improve data availability in health risk assessment of chemicals and fill information gaps there is a need to facilitate the use of non-standard toxicity studies, i.e. studies not conducted according to any standardized toxicity test guidelines. The purpose of this work was to propose criteria and guidance for the evaluation of reliability and relevance of non-standard in vivo studies, which could be used to facilitate systematic and transparent evaluation of such studies for health risk assessment. Another aim was to propose user friendly guidance for reporting of non-standard studies intended to promote an improvement in reporting of studies that could be of use in risk assessment. Requirements and recommendations for the design and execution of in vivo toxicity studies were identified from The Organisation for Economic Co-operation and Development (OECD) test guidelines, and served as basis for the data evaluation criteria and reporting guidelines. Feedback was also collected from experts within the field of toxicity testing and risk assessment and used to construct a two-tiered framework for study evaluation, as well as refine the reporting guidelines. The proposed framework emphasizes the importance of study relevance and an important aspect is to not completely dismiss studies from health risk assessment based on very strict criteria for reliability. The suggested reporting guidelines provide researchers with a tool to fulfill reporting requirements as stated by regulatory agencies. Together, these resources provide an approach to include all relevant data that may fill information gaps and reduce scientific uncertainty in health risk assessment conclusions, and subsequently also in chemical policy decisions.
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| 6. |
- Beronius, Anna, et al.
(författare)
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Testing and refining the Science in Risk Assessment and Policy (SciRAP) web-based platform for evaluating the reliability and relevance of in vivo toxicity studies
- 2018
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Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 38:12, s. 1460-1470
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Tidskriftsartikel (refereegranskat)abstract
- The Science in Risk Assessment and Policy (SciRAP) web-based platform was developed to promote and facilitate structure and transparency in the evaluation of ecotoxicity and toxicity studies for hazard and risk assessment of chemicals. The platform includes sets of criteria and a colour-coding tool for evaluating the reliability and relevance of individual studies. The SciRAP method for evaluating in vivo toxicity studies was first published in 2014 and the aim of the work presented here was to evaluate and develop that method further. Toxicologists and risk assessors from different sectors and geographical areas were invited to test the SciRAP criteria and tool on a specific set of in vivo toxicity studies and to provide feedback concerning the scientific soundness and user-friendliness of the SciRAP approach. The results of this expert assessment were used to refine and improve both the evaluation criteria and the colour-coding tool. It is expected that the SciRAP web-based platform will continue to be developed and enhanced to keep up to date with the needs of end-users.
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| 7. |
- Carlsson, Gunnar, et al.
(författare)
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Thyroid disruption properties of three indoor dust chemicals tested in Silurana tropicalis tadpoles
- 2019
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Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 39:9, s. 1248-1256
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Tidskriftsartikel (refereegranskat)abstract
- Indoor dust contains a multitude of industrial chemicals, and ingestion of dust is considered an important exposure route to organic contaminants. Some of these contaminants have been shown to interfere with the thyroid system, which may result in significant consequences on public health. The amphibian metamorphosis is a thyroid hormone-dependent process, which can be used as an in vivo model for studies on thyroid hormone-disrupting potency. Three contaminants of indoor dust were tested on metamorphosing Silurana (Xenopus) tropicalis tadpoles. The tested chemicals were Tris (1,3-dichloroisopropyl) phosphate (TDCiPP), tetrabromobisphenol-A (TBBPA) and propylparaben (PrP). Measurements reflecting general growth, development progress and thyroid epithelial cell height were performed on the exposed tadpoles as well as chemical analyses of the exposure water. It was shown that TDCiPP acts as a thyroid hormone-disrupting chemical in metamorphosing tadpoles by causing increased epithelial cell height in thyroid glands after exposure to a nominal concentration of 0.010 mg/L and in higher concentrations. TBBPA caused reductions in general growth of tadpoles at the nominal concentration 0.125 mg/L, and PrP caused acute toxicity at the nominal concentration 12.5 mg/L. However, no evident indications of specific thyroid-disrupting effects caused by TBBPA or PrP were observed.
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| 8. |
- Chen, Xiao, et al.
(författare)
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The association between dietary cadmium exposure and renal dysfunction - the benchmark dose estimation of reference levels : the ChinaCad study
- 2018
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Ingår i: Journal of Applied Toxicology. - : John Wiley & Sons. - 0260-437X .- 1099-1263. ; 38:10, s. 1365-1373
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Tidskriftsartikel (refereegranskat)abstract
- The tolerable dietary intake of cadmium was recommended at provisional tolerable monthly intake of 25gkg(-1) body weight. However, several studies indicated that this tolerable level should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using a benchmark dose (BMD) approach. A total of 790 subjects (302 men and 488 women) living in control and cadmium-polluted areas were included. The dietary cadmium intake was estimated by a food survey. Blood cadmium, urinary cadmium and renal function markers (microalbuminuria, N-acetyl--d-glucosaminidase [NAG] and its isoform B [NAGB], (2)-microglobulin and retinol binding protein) in urine were measured. We calculated the 95% lower confidence bounds of BMD (BMDLs) of cumulative cadmium intake. In control and two polluted areas, the median cumulative cadmium intake was 0.5, 2.1 and 11.1g. The odds ratio of the intermediate (1.0-3.0g), second highest (3.0-11.0g) and the highest cumulative cadmium intake (>11.0g) compared with the lowest cumulative cadmium intake (<1.0g) were 2.8 (95% CI: 1.4-5.8), 8.1 (95% CI: 3.8-17.2) and 11.4 (95% CI: 6.5-26.4) for urinary NAG and 6.6 (95% CI: 3.2-13.8), 14.8 (95% CI: 6.8-32.2) and 22.5 (95% CI: 10.7-47.5) for urinary NAGB. The BMDLs of cumulative cadmium intake were 1.1-1.2g (benchmark response [BMR]=5%) for urinary NAG, and were 0.7-0.9g (BMR=5%) for urinary NAGB, and were 1.3-1.4g (BMR=5%) for urinary (2)-microglobulin. The BMDLs of cumulative cadmium intake in a Chinese population were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection. Several studies indicated that the tolerable dietary intake of cadmium should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using benchmark dose (BMD) approach. The lowest BMD lower bound confidence limits of cumulative cadmium intake were 0.7-0.9g (benchmark response=5%). The BMD lower bound confidence limits of cumulative cadmium intake were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection.
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