Placenta transfer study in non-human primate (NHP) is one of the crucial components in the assessment of developmental toxicity because of the similarity between NHP and humans. To establish the method to determine placenta transfer in non-human primate, toxicokinetics of valproic acid (VPA), a drug used to treat epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. After mating, pregnancy-proven females were daily administered with VPA at dose levels of 0, 20, 60 and 180 mg/kg by oral route during the organogenesis period from gestation day (GD) 20 to 50. Concentrations of VPA and its metabolite, 4-ene-VPA, in maternal plasma on GDs 20 and 50, and concentrations of VPA and 4-ene-VPA in placenta, amniotic fluid and fetus on GD 50 were analyzed using LC/MS/MS. Following single oral administration of VPA to pregnant monkeys, concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma from all treatment groups up to 4-24 hours post-dose, demonstrating that VPA was absorbed and the monkeys were systemically exposed to VPA and 4-ene-VPA. After repeated administration of VPA to the monkeys, VPA was detected in amniotic fluid, placenta and fetus from all treatment groups, demonstrating that VPA was transferred via placenta and the fetus was exposed to VPA, and the exposures were increased with increasing dose. Concentrations of 4-ene-VPA in amniotic fluid and fetus were below the limit of quantification, but small amount of 4-ene-VPA was detected in placenta. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at dose levels of 20, 60 and 180 mg/kg during the organogenesis period. VPA was transferred via placenta and the fetus was exposed to VPA with dose-dependent exposure. The metabolite, 4-ene VPA, was not detected in both amniotic fluid and fetus, but small amount of 4-ene-VPA was detected in placenta. These results demonstrated that proper procedures to investigate placenta transfer in NHP, such as mating and diagnosis of pregnancy via examining gestational sac with ultrasonography, collection of amniotic fluid, placenta and fetus after Caesarean section followed by adequate bioanalysis and toxicokinetic analysis, were established in this study using cynomolugus monkeys.
Kim, Ki-Yeon;Park, Jae-Beom;Kim, Chi-Nyon;Lee, Kyung-Jong
Journal of Preventive Medicine and Public Health
/
v.38
no.2
/
pp.141-146
/
2005
Objectives: Particulate contaminants, such as total and respirable dusts, can harm the health of farm workers via several routes. The principal aims of this field study were to determine the concentrations and emissions of particulate contaminants: total and respirable dusts, in the different types of swine houses used in Korea, and allow objective comparison between Korea and the other countries in terms of swine housing types. Methods: The swine houses investigated in this research were selected with respect to three criteria: the manure removal system, ventilation mode and growth stage of pigs. Measurements of total and respirable dust concentrations and emissions in the swine houses were carried out on 5 housing types at 15 different farm sites per housing type. The swine houses investigated were randomly selected from farms situated within the central districts in Korea: province of Kyung-gi, Chung-buk and Chung-nam. Results: The total and respirable dust concentrations in the swine houses averaged $1.88\;and\;0.64mg/m^3$, ranging from $0.53\;to\;4.37mg/m^3$ and from $0.18\;to\;1.68mg/m^3$, respectively. The highest concentrations of total and respirable dusts were found in the swine houses with deep-litter bed systems: $2.94mg/m^3\;and\;1.14 mg/m^3$, while the lowest concentrations were found in the naturally ventilated buildings with slats: $0.83mg/m^3\;and\;0.24mg/m^3$, respectively (p<0.05). All the swine houses investigated did not exceed the threshold limit values (TLVs) for total ($10mg/m^3$) and respirable ($2.5mg/m^3$) dusts. The mean emissions of total and respirable dusts, per pig (75 kg in terms of live weight) and area ($m^2$), from the swine houses were 97.33 and 9.55 mg/h/pig and $37.14\;and\;12.83mg/h/m^2$, respectively. The swine houses with deep-litter bed systems showed the highest emissions of total and respirable dusts (p<0.05). However, the emissions of total and respirable dusts from the other swine houses were not significantly different (p>0.05). Conclusion: The concentrations and emissions of total and respirable dusts were relatively higher in the swine houses managed with deep-litter bed systems and ventilated naturally of the different swine housing types tested. In further research, more farms than the number used in this research should be investigated, which will present objective and accurate data on the concentrations and emissions of total and respirable dusts in Korean swine houses. In addition, personal sampling should be performed to objectively assess the exposure level of farm workers to particulate contaminants.
N-nitrosamines are the nitroso compounds which are produced by nitrosation reactions of the secondary amine and nitrite under acidic conditions. Approximately 300 species of N-nitrosamine have been tested for carcinogenicity in laboratory experiments, with 90% of them demonstrated carcinogenic effects different animal species, including higher primates. In 1978, IARC classified NDMA and NDEA as Group 2A, and NDPA, NDBA, NPIP, NPYR and NMOR as Group 2B. In this study, we established pretreatment and analytical method for N-nitrosamines (NDMA, NDEA, NMEA, NDPA, NDBA, NPIP, NPYR and NMOR) in human urine for biological monitoring of N-nitrosamines. The analytes were extracted using solid phase extraction (SPE), then quantitative analysis was performed by LC-(APCI)-MS/MS. The accuracies of the established method were between 85.8~108.7% and precisions were lower than 20%. The limit of detection (LOD) were between 0.0002 (NDBA) and 0.0793 (NDMA) ng/ml. The linearity obtained was satisfying for the 8 N-nitrosamines, with a coefficient of determination ($r^2$) higher than 0.999. The mean concentrations of N-nitrosamines in the urine were 2.645 mg/g creatinine for NDMA, 0.067 mg/g creatinine for NDEA, 0.009 mg/g creatinine for NMEA, 0.011 mg/g creatinine for NDBA, 0.271 mg/g creatinine for NPIP and 0.413 mg/g creatinine for NPYR. NDPA and NMOR were not detected. It can be used as a instrumental methodology for evaluation and risk assessment of human exposure to N-nitrosamines for the further research.
Cypress woods treated individually with boric acid (BA4), ammonium pentaborate (APB4), or BA4/APB4 additives were examined for combustion gases. Each of the specimens was painted with a 4 wt% solution of boron compounds three times. Dried at room temperature, the combustion gas was analyzed using a cone calorimeter (ISO 5660-1). Consequently, the second maximum oxygen consumption rate of the specimen treated with boron compounds was 0.1067 to 0.1246 g/s, which was 5.3 to 18.9%, respectively lower than that of the blank specimen. The specific extinction area of specimens treated with BA4 and APB4 was also 2.0 to 19.0% lower, respectively. However, treated with BA4/APB4 showed 21.2% higher than that of the blank specimen. The maximum carbon monoxide concentration of the specimens with boron compounds was reduced by 0 to 25%. It was estimated to be 1.6 to 2.2 times higher than the permissible exposure limits by Occupational Safety and Health Administration (OSHA), indicating a fatal toxicity. The boron compounds were effective in reducing carbon monoxide, but didn't meet the OSHA limit. The boron compound inhibited the burning behavior of the cypress wood, which suppressed the second maximum oxygen consumption rate by 5.3 to 18.9% and the maximum carbon monoxide generation by 0 to 25%.
Kim, Ki Youn;Park, Jae Beom;Kim, Chi-Nyon;Lee, Kyung Jong
Journal of Korean Society of Occupational and Environmental Hygiene
/
v.16
no.1
/
pp.36-43
/
2006
The principal aim of this field study was to determine the concentrations and emissions of gaseous contaminants such as ammonia and hydrogen sulfide in the different types of pig buildings in Korea and allow objective comparison between Korea and the other countries in terms of pig housing types. This field study was performed from May to June and from September to October in 2002. Pig buildings investigated in this research were selected in terms of three criteria; manure removal system, ventilation mode and growth stage of pig. Measurements of concentration and emission of ammonia and hydrogen sulfide in the pig buildings were done in 5 housing types and the visited farms were 15 sites per each housing type. Concentrations of ammonia and hydrogen sulfide were measured at three locations of the central alley in the pig building and emission rates of them were estimated by multiplying the average concentration($mg/m^3$) measured near the air outlet by the mean ventilation rate($m^3/h$) and expressed either per pig of liveweight 75kg(mg/h/pig) or per area($mg/h/m^2$). Concentrations of ammonia and hydrogen sulfide in the pig buildings were averaged to 7.5 ppm and 286.5 ppb and ranged from 0.8 to 21.4 ppm and from 45.8 to 1,235 ppb, respectively. The highest concentrations of ammonia and hydrogen sulfide were found in the mechanically ventilated buildings with slats; 12.1 ppm and 612.8 ppb, while the lowest concentrations of ammonia and hydrogen sulfide were found in the pig buildings with deep-litter bed system(2.2 ppm) and the naturally ventilated pig buildings with manure removal system by scraper(115.2 ppb), respectively(p<0.05). All the pig buildings were investigated not to exceed the threshold limit values(TLVs) of ammonia(25 ppm) and hydrogen sulfide(10 ppm). The mean emissions of ammonia and hydrogen sulfide per pig(75kg in terms of liveweight) and area($m^2$) from pig buildings were 250.2 mg/h/pig and 37.8 mg/h/pig and $336.3mg/h/m^2$ and $50.9mg/h/m^2$, respectively. The pig buildings with deep-litter bed system showed the lowest emissions of ammonia and hydrogen sulfide(p<0.05). However, the emissions of ammonia and hydrogen sulfide from the other pig buildings were not significantly different(p>0.05). Concentrations and emissions of ammonia and hydrogen sulfide were relatively higher in the pig buildings managed with deep-pit manure system with slats and mechanical ventilation mode than the different pig housing types. In order to prevent pig farm workers from adverse health effect caused by exposure to ammonia and hydrogen sulfide in pig buildings, they should wear the respirators during shift and be educated sustainably for the guideline related to occupational safety.
Journal of Korean Society of Occupational and Environmental Hygiene
/
v.1
no.2
/
pp.181-191
/
1991
The present study determined the overall noise level and the distribution of sound pressure level over audible frequency range of noise produced at various work sites. Work-related noise greater than 80dBA produced from 98 separate work sites at 37 manufacturing companies and machine shops were analysed for the overall sound level (dBA) and frequency distribution. In addition, to determine the possible hearing loss related to work site noise, a hearing test was also conducted on 1,374 workers in these work sites. The results of the study were as follows ; 1. Of the total 98 work sites, 57 work sites(58.2%) produced noise exceeding threshold limit value (${\geq}90dBA$) set by the Ministry 01 Labor. In terms of different manufacturing industries the proportion of work sites which exceeded 90dBA was the highest for the cut-stone products industry with 6/6 work sites and lowest for the commercial printing industry with 1/13 work sites. 2. The percentage of workers who were exposed to noise greater than 90dBA was 19.8% (1,040 workers) 01 the total 5,261 workers. In terms of different industries, cut-stone products industry had the most workers exposed to noise exceeding 90dBA with 82.8%, textile bleaching and dyeing industry was next at 30.6% followed by fabricated metal products industry with 27.9%, plastic products manufacturing industry had the lowest percentage of workers exposed to 90dBA exceeding noise with 4.5%. 3. There was a statistically significant correlation between the frequency of noise-induced hearing loss and the percentage of workers exposed to noise exceeding 90dBA (P<0.05). 4. The frequency analysis of noise produced at the 98 work sites revealed that 44 work sites (44.9%) had the maximum sound pressure level at high-frequencies greater than 2KHz. In addition, significantly higher sound pressure level was detected at the high-frequencies at 90dBA exceeding work sites as compared to below 90dBA work sites (P<0.01). 5. The differences in sound level meter's A-and C-weighted sound pressure levels were analysed by frequencies. Of the 28 work sites which showed 0-1 dB difference in the two weighted sound levels, 20 work sites (71.4%) had significantly higher sound pressure levels at high-frequencies greater than 2KHz (P<0.01). Furthermore, there was a tendency for higher sound pressure levels to occur in the high-frequency range as the differences in the two weighted sound levels decreased.
Journal of Korean Society of Occupational and Environmental Hygiene
/
v.17
no.3
/
pp.245-253
/
2007
This research was performed to evaluate the airborne personal concentration of hazardouse materials during the process of ship construction and surveyed from May 23 to June 30, 2007 in Kyungnam West Distirct, Korea. The subject was 94 ship construction workers exposed to welding fume and respirable particulate. The airborne concentrations of those were compared to Permissible Exposure Limit(PEL) from the Ministry of Labor in Korea. The airborne concentration of 23 samples(48.9%) of welding fumes was less than $5mg/m^3$, that of 16 (34.0%) was between 5 and $10mg/m^3$, and that of 8 (17.0%) was greater than $10mg/m^3$. The airborne concentration of 27 (57.4%) of respirable particulate masses was less than $5mg/m^3$ and the othere are greater than $5mg/m^3$. The welding fumes were identified containing the heavy metasl such as Fe, Mn, Zn, Mg, Ca, and Cu. The respirable particulates has similiar tendency with welding fumes in the component of heavy metals. But the concentration of Ca, Cu, Cr, and Ni turned out to be higher in welding fumes. Twenty (42.6%) of the 47 samples of welding fumes were exceeded PEL. In the heavy metals in welding fumes, ten (21.3%) of the 47 samples of Mn were exceeded PEL. Based on the results, the higher airborne hazardous materials were still exposed to wokers in ship construction process. It is suggested that the appropriate engineering control be applied to minimize the exposed cocnetration in ship building processes.
House dust mite allergens have been well established as sensitizing agents that are important in the induction of allergic diseases. In order to analyze epitopes of the allergen and to develop a quantitative method of the allergen exposure, monoclonal antibodies against a recombinant Der p 2 (rDer p 2), one of the major allergens of Dermatophogoides pteronyssinus, were produce. Four monoclonal antibodies produced wee species-specific and did not cross-react to the D. farinae crude extract. Two of the monoclonal antibodies were found to be IgG1 and the others were IgM. For the analysis of epitopes, a Der p 2 cDNA encoding 126 amino acids (aa) was dissected into three fragments with several overlapping peptides, A (aa residues 1-49), B (44-93), and C fragment (84-126). Three monoclonal antibodies showed reactivities to the recombinant B fragment and to the full-length rDer p 2, but one monoclonal antibody reacted only with the full-length rDer p 2. Two-site capture ELISA was developed using two different monoclonal antibodies for quantitating Der p2 in house dust. The sensitivity limit was 4ng/ml with rDer p2 and $8{\;}\mu\textrm{g}/ml$ with the d. pteronyssinus crude extract. The result suggested that the assay using monoclonal antibodies against rDer p2 could be useful for the environmental studies and for the standardization of mite allergen extracts.
Kim, Seung-Won;Jang, Young-Jae;Park, Young-Hwan;Park, Cheol-Woo
Journal of the Korea Concrete Institute
/
v.24
no.5
/
pp.543-551
/
2012
Road pavements in Korea generally show shorter service life than the predicted one. There are many reasons for this phenomenon including increased traffic load and other attacks from exposure conditions. In order to extend a service life and upgrade the pavement, a new multi-functional composite pavement system is being developed in Korea. This study is to investigate the performances of fiber-reinforced lean concrete for pavement base. This study considered mineral admixtures of fly ash and reject ash. The reject ash is defined as ash that does not meet the specifications for fly ash so that it cannot be used as a supplemental material for cement replacement. Due to the inherent property of lean concrete, compaction during the fabrication of specimens is a key factor. Therefore, this study suggests an appropriate compaction method. From the test results, the compressive strengths of the concrete satisfied the required limit of 5 MPa at 7 days. When a compaction roller was used to mimic actual field conditions, the strength development seemed to be influenced by the compaction energy rather than hydration of cement itself.
Objectives: Microcystin (MC) produced during cyanobacterial blooms is a worldwide problem presenting a serious health threats to humans and ecosystems. During July through October of 2013, the Ilwol Reservoir experienced a high biomass of phytoplankton (maximum $211.7mg/m^3$ of Chlorophyll-a) containing the toxigenic cyanobacterium Oscillatoria sp. The aim of this study is to analyze MC concentration in the reservoir water, as well as in representative fish species (Carassius cuvieri, Carassius auratus, Channa argus). We also evaluated the human health risk of exposure to MCs accumulated in the fish. Methods: Concentrations of MCs in the water and fish samples were analyzed by liquid chromatography with a triple quadrupole tandem mass spectrometer (LC/MS/MS) and enzyme-linked immunosorbent assay (ELISA). Results: The total levels of four MC variants, including MC-LR, MC-RR, MC-YR and MC-LA were below the WHO drinking water guideline limit (1 ug MC-LR per liter) both for the dissolved and particulate fraction present in the water samples. The mean MC concentrations in the livers of all species were significantly higher than in the gills (p < 0.01) and muscles (p < 0.05). The values of estimated daily intake of MCs in muscles, the edible part of the fish, would be only $0.005-0.015{\mu}g/kg{\cdot}day$, much lower than WHO's provisional tolerable daily intake of $0.04{\mu}g/kg{\cdot}day$. Conclusion: This study suggests that, owing to the spatial distribution or temporal variation of MC, there is a need for careful monitoring of cyanotoxin in reservoir water and aquatic animals to protect public health.
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