• Title/Summary/Keyword: Chronic toxicity studies

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Histopathology and residues in fresh water fish exposed to acute and chronic copper and mercury toxicity

  • Sawsan, H.A.;Amira, H.M.;Mostafa, M.B.;Nashaat, AM.M.
    • Journal of fish pathology
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    • v.30 no.2
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    • pp.115-134
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    • 2017
  • A total number of 668 apparently healthy fish were obtained from farm to study the effect of two heavy metals (Copper and Mercury) on histopathology of liver, kidney, spleen, gills and muscles also residues in muscles. The $LC_{50}$/96 hr. of Cu and Hg were estimated and fish exposed to 1/2 $LC_{50}$ for 7 days and for 1/10 $LC_{50}$ for 8 weeks from each product separately. Histopathological findings in acute and chronic mercuric chloride toxicity revealed degeneration and necrosis in the glomeruli, interstitium tissue and epithelium lining renal tubules. The tubular epithelium became necrotic at several places. Eosinophilic hyaline droplets is exist in the cytoplasm of the necrosed cells. Degenerative changes and hyperactivity in melanomachrophage center was seen in the spleen together with some necrotic areas. Necrosis and aggregation of melanomachrophage were seen in the hepatic cells, Hepatic cells showed vacuolar degeneration in the hepatic cells. Gills showed loss in the lamellae of the filaments associated with edema, inflammatory cells infiltration and haemorrhages in the arch. The sarcoplasm of the bundles of the skeletal muscle showed granular degeneration and focal inflammatory cells infiltration between the hyalinized bundles. Mercury residues obtained from these studies in the acute toxicity were 0.22 ppm/gm in the 2nd day, 0.411 ppm/gm in the $5^{th}$ day ended with 0.96 ppm/gm in the $7^{th}$ day. In chronic toxicity it was 1.1320, 1.7140, 2.3620 and 3.5640 ppm/gm respectively from the $2^{nd}$ to the $8^{th}$ week of exposure. In acute and chronic copper toxicity, there was degenerative changes in renal tubules. Melanophores aggregation in the wall of the blood vessels of the spleen and depletion of some of the melanophores in the melanomachrophage were seen together with necrosis in some areas. Congested Mvs (Micro vessels) and vacuolation of hepatocytes were observed. Some areas of hemorrhage and melanophores vacuolar degeneration in the liver were seen. There was mitosis in some areas with displesia of hepatopancreatic cells and eosinophilic granular cells aggregation. Zymogen granules disappeared and there were dyplastic hepatocytes. Congestion in the blood vessels of the gill filaments, associated with massive number of granular eosinophilic cells infiltration were seen in the base of the filaments. There were sever vacuolization and hyalinization in the skeletal muscle bundles. Detection of residues of copper sulfate revealed increase of the amount of copper measured in ppm/gm comparing to the normal control starting from 0.60 ppm/g in the $2^{nd}$ day, 0.67 ppm/g in the $5^{th}$ day and 0.67 ppm/g in the $7^{th}$ day. Result obtained in chronic copper sulfate toxicity revealed gradual increase of the amount of copper which ranged from 0.18 ppm/g at the $2^{nd}$ week to 0.21 ppm/g in the $8^{th}$ week of exposure.

Effects of Didecyldimethylammonium Chloride (DDAC) on Sprague-Dawley Rats after 13 Weeks of Inhalation Exposure

  • Kim, Yong-Soon;Lee, Sung-Bae;Lim, Cheol-Hong
    • Toxicological Research
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    • v.33 no.1
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    • pp.7-14
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    • 2017
  • Didecyldimethylammonium chloride (DDAC) is used in many types of biocidal products including tableware, carpets, humidifiers, and swimming pools, etc. In spite of increased chances of DDAC exposure through inhalation, studies on the inhalation toxicity of DDAC are not common even though the toxicity of DDAC might be significantly higher if it were to be administered through routes other than the respiratory system. DDAC aerosols were exposed to Sprague-Dawley rats in whole body exposure chambers for a duration of 13 weeks. The Mass Median Aerodynamic Diameters of the DDAC aerosol were $0.63{\mu}m$, $0.81{\mu}m$, and $1.65{\mu}m$, and the geometric standard deviations were 1.62, 1.65, and 1.65 in the low ($0.11{\pm}0.06mg/m^3$), the middle ($0.36{\pm}0.20mg/m^3$) and the high ($1.41{\pm}0.71mg/m^3$) exposure groups, respectively. Body weight was confirmed to be clearly influenced by exposure to DDAC and mean body weight was approximately 35% lower in the high ($1.41{\pm}0.71mg/m^3$) male group and 15% lower in the high ($1.41{\pm}0.71mg/m^3$) female group compared to that of the control group. In the bronchoalveolar lavage fluid assay, the levels of albumin and lactate dehydrogenase had no effect on DDAC exposure. The lung weight increased for the middle ($0.36{\pm}0.20mg/m^3$) and the high ($1.41{\pm}0.71mg/m^3$) concentrations of the DDAC exposure group, and inflammatory cell infiltration and interstitial pneumonia were partially observed in the lungs of the middle ($0.36{\pm}0.20mg/m^3$) and the high ($1.41{\pm}0.71mg/m^3$) exposure groups. However, severe histopathological symptoms, including proteinosis and/or fibrosis, were not found. Based on the results of the changes in the body weight and lung weight, it is considered that the NOAEL (no-observed adverse effect) level for the 13-week exposure duration is $0.11mg/m^3$.

Methylated Organic Metabolites of Arsenic and their Cardiovascular Toxicities

  • Bae, Ok-Nam;Lim, Kyung-Min;Noh, Ji-Yoon;Kim, Keun-Young;Lim, Eun-Kyung;Chung, Jin-Ho
    • Toxicological Research
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    • v.24 no.3
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    • pp.161-167
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    • 2008
  • Recently, arsenic-toxicity has become the major focus of strenuous assessment and dynamic research from the academy and regulatory agency. To elucidate the cause and the mechanism underlying the serious adverse health effects from chronic ingestion of arsenic-contaminated drinking water, numerous studies have been directed on the investigation of arsenic-toxicity using various in vitro as well as in vivo systems. Neverthless, some questions for arsenic effects remain unexplained, reflecting the contribution of unknown factors to the manifestation of arsenic-toxicity. Interestingly, very recent studies on arsenic metabolites have discovered that trivalent methylated arsenicals show stronger cytotoxic and genotoxic potentials than inorganic arsenic or pentavalent metabolites, arguing that these metabolites could play a key role in arsenic-associated disorders. In this review, recent progress and literatures are summarized on the metabolism of trivalent methylated metabolites and their toxicity on body systems including cardiovascular system in an effort to provide an insight into the future research on arsenic-associated disorders.

Acute Nitrate Nitrogen Toxicity in Juvenile Blackhead Seabream Acanthopagrus schlegelii (질산성 질소가 감성돔(Acanthopagrus schlegelii) 치어에 미치는 급성 독성 영향)

  • Seo, Seok;Choi, Eun Ji;Park, JeongHwan
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.52 no.3
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    • pp.268-273
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    • 2019
  • This study evaluated acute nitrate nitrogen ($NO_3-N$) toxicity in juvenile blackhead seabream Acanthopagrus schlegelii. Seventy juveniles (Trial A, $7.1{\pm}0.6g$) and nine juveniles (Trial B, $71.3{\pm}3.5g$) per 70 L tank were exposed to $NO_3-N$ concentrations of 0, 500, 1500, 2500, 3500, and 4500 mg/L and 0, 600, 1200, 1800, 2400, and 3000 mg/L, respectively, in triplicate for 7 days. In Trial A, all fish exposed to 3500 and $4500mg\;NO_3-N/L$ died within 48 h; in Trial B, all fish exposed to $3000\;NO_3-N/L$ died after 120 h. The $96\;LC_{50}$ and $168\;LC_{50}$ were 2505 and $1806mg\;NO_3-N/L$, respectively, in Trial A, and 2663 and $2377mg\;NO_3-N/L$ in Trial B. Large juveniles were more resistant to $NO_3-N$ than small juveniles. The results of acute $NO_3-N$ toxicity studies provide important data for subsequent chronic toxicity studies.

PATHOLOGICAL STUDIES ON THE CHRONIC TOXICITY OF METHAMPHETAMINE ADMINISTRATION

  • Rim, Byung-Moo;Cho, Gye-Myung;Chang, Jae-Hong
    • Toxicological Research
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    • v.9 no.2
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    • pp.233-240
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    • 1993
  • Toxic effects of chronic adminstration of methamphetamine (MA) to SD rats were studied in respect to histopathological changes induced in each organ. In experimental groups liver weight decreased and brain weights increased markedly compared with controls in the 12th month after subcutaneous injection of 0.5 mg and 5mg/kg/BW MA. Serum alkaline phosphotase levels increased, but marked decrease of cholesterol, triglyceride, and BUN levels were checked depending on both the dose of MA and duration of treatment.

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Toxicity of disulfiram, a therapeutic agent for chronic alcoholism, to mouse spleen cells

  • Han, Yong;Joo, Hong-Gu
    • Journal of Preventive Veterinary Medicine
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    • v.42 no.4
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    • pp.177-181
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    • 2018
  • Disulfiram is a drug used to treat alcohol dependence. Recent studies have shown that disulfiram also has anti-cancer effects. Considering that many anti-cancer agents have side effects, including immunosuppression, it is important to check if disulfiram has some cytotoxicity to immune cells. In this study, mouse spleen cells were treated with disulfiram and the metabolic activity was measured. Disulfiram increased the cell death of spleen cells according to annexin V-FITC/PI staining analysis. In addition, disulfiram decreased the mitochondrial membrane potential of spleen cells. The toxicity of disulfiram was concentration dependent. Interestingly, disulfiram affected the population of lymphocytes and the subset of spleen cells was altered. This study provides clinicians and researchers with valuable information regarding the toxicity of disulfiram to mouse spleen cells, particularly lymphocytes.

Development of Korean Chemical Ranking and Scoring System (CRS-Korea) and its Application to Prioritizing National Toxic Chemicals (화학물질 우선순위 선정 기법(CRS-Korea)의 개발과 적용)

  • Park Hoa-Sung;Kim Ye-shin;Lee Dong Soo;Shin Yong-seung;Choi Seung-pil;Park Seong-eun;Kim Myung-hyun;Yang Ji-yeon;Shin Dong-chun
    • Environmental Analysis Health and Toxicology
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    • v.20 no.2 s.49
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    • pp.109-121
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    • 2005
  • A chemical ranking and scoring (CRS-Korea) system was developed and proposed to use as the first step to prioritize the toxic chemicals for the purpose of monitoring and detailed risk assessment that might follow as necessary. The CRS-Korea system takes a basic concept of risk assessment (both human health risk and ecological risk) in that risk score is determined by the product of toxicity score and exposure score. Included in the toxicity category are acute toxicity, chronic/sub -chronic toxicity, carcinogenicity, and other toxicity. The exposure category consists of quantity released to the environment, bioconcentration, and persistence. A consistent scheme and a comprehensive chemical data base are offered in the CRS-Korea system to calculate a score for the each component in the two categories by using specific physicochemical, fate, and toxic properties and the quantity of the chemical used. The toxicity score is obtained by adding up all the individual scores for the components in the toxicity category. The exposure score is determined by multiplication of the score of the quantity released with the sum of persistent score and bioconcentration score. Equal weight is given to the toxicity score and the exposure score. As the CRS-Korea system was applied to identify 50 national priority chemicals, it was found that significant data gap exists on toxicity and fate properties and that the uncertainty associated with estimating the quantify released to the environment is notably high. The proposed CRS system is only a screening tool in the first step toward the priority setting and should be used with expert judgement and other considerations necessary.

Effect of Chronic Toxicity by Waste Microplastics (PET) on Daphnia magna (폐 미세플라스틱(PET)의 물벼룩 만성독성 연구)

  • Han, Bomi;Park, GeonU;Yoo, Seungwoo;Kim, Changhae;Jung, Jinho;Na, Joorim
    • Ecology and Resilient Infrastructure
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    • v.8 no.4
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    • pp.281-289
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    • 2021
  • Commercially used disposable cups undergo fragmentation in the environment and become microplastics (MPs). These MPs can be ingested by aquatic organisms and cause a range of adverse effects. We assessed the acute and chronic toxicity of disposable cup-derived MP fragments in Daphnia magna. MP fragments were identified as a polyethylene terephthalate (PET) fragment with a size of 33.18 ± 7.76 ㎛. The presence of three additives including 1- Propanone. 1-phenyl-3-[2-(phenylmethoxy)phenyl]-, p-Xylene and ethylbenzene was analyzed from MP fragments. The 48 h acute toxicity revealed that 20 % of immobilization and mortality were found at the highest concentration of PET MP (200 mg L-1). The 21 d chronic toxicity revealed that PET MP fragments significantly (p < 0.05) more reduced survival rate (31 %), total offspring (52 %) in D. magna compared with control group. The developmental abnormality of offspring (3.5%) by PET MP fragments was significantly (p < 0.05) higher than control groups (0.3%). These results are possibly induced by gut blocking by ingestion of MP fragments and their longer retention time. These findings indicate that the fragmentation of disposable cups (PET polymers) into small-sized MP fragments pose a significant ecological risk to aquatic organisms. Further studies are required to elucidate the underlying toxicity mechanisms.

Arsenic Toxicity in Male Reproduction and Development

  • Kim, Yoon-Jae;Kim, Jong-Min
    • Development and Reproduction
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    • v.19 no.4
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    • pp.167-180
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    • 2015
  • Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children's health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity.

Chronic Toxicity of the Triazole Fungicide Tebuconazole on a Heterocystous, Nitrogen-Fixing Rice Paddy Field Cyanobacterium, Westiellopsis prolifica Janet

  • Nirmal Kumar, J.I.;Bora, Anubhuti;Amb, Manmeet Kaur
    • Journal of Microbiology and Biotechnology
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    • v.20 no.7
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    • pp.1134-1139
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    • 2010
  • This study explored the chronic effects of different doses of the triazole fungicide tebuconazole on the growth, and metabolic and enzymatic functions of the filamentous paddy field cyanobacterium, Westiellopsis prolifica Janet. The growth of the cyanobacterium was determined by an estimation of the change in pigment contents. Chlorophyll-a, carotenoids, and accessory pigments such as phycocyanin, allophycocyanin, and phycoerythrin were shown to decline over a 16-day period by a factor of 92%, 93%, 83%, 95%, and 100%, respectively, with increasing doses of the fungicide. Metabolic and enzymatic activities were also adversely affected. Over the 16 days, a gradual rise in total phenol content was recorded when Westiellopsis prolifica Janet was treated with 60 ppm of the fungicide, despite the reduction in carbohydrates, proteins, and amino acids by 96%, 92%, and 90%, respectively. Moreover, the enzymes nitrate reductase (NR), glutamine synthetase (GS), and succinate dehydrogenase (SDH) also registered reductions of 93%, 90%, and 98%, respectively. This study indicates that tebuconazole, although an important fungicide used extensively in rice fields, exhibits an inhibitory effect on the growth and metabolic activities of Westiellopsis prolifica Janet and hence possibly on other varieties as well.