• Toxicological Research
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• 제30권2호
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• pp.121-130
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• 2014

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

• 한국식품조리과학회지
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• 제14권5호
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• pp.475-481
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• 1998

돼지고기와 챔을 이용한 찌개에서 생성되는 돌연변 이원성과 김치 , 표고버섯, 파, 마늘이 부재료로 첨가되었을 때의 억제효과를 검토하고 국산햄과 외국산챌의 차이를 알아보고자 변이원으로 4-NQO, Trp-p-1을 사용하여 염기치환형 변이균주인 Salmonella typhimurium TA100을 이용한 Ames test를 실시하였다. 1. 0.025-0.02 g/Plate 농도에서, 김치는 가열했을때 변이원성이 나타나지 않았고 4-NQO, Trp-p-1의 변미원성을 효과적으로 억제하였다. 햄과 돼지고기는 가열시 변이원이 자체적으로 생성되었고 돼지고기 0.02 g/plate 농도에서 가장 큰 값을 나타내어 육가공품에 첨가된 아질산염에 대한 안전성을 확보할 수 있었다. 2.가열된 돼지고기와 햄의 변이원성에 대하여 대체로 김치 첨가시 억제효과가 가장 컸고, 표고버섯 한가지보다는 표고버섯에 파 ,마늘을 함께 첨가했을때 억제효과가 더 컸다. 3. 외국산햄은 국산햄과 달리 항산화제인 ascorbic acid가 더 많이 첨가되어 있어 0.02g/plate 농도에서 가열에 의해 변이원이 생성되지 않았고 변이원 존재 시 국산햄보다 낮은 변이원성을 나타내었다.

• Toxicological Research
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• 제31권1호
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• pp.69-75
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• 2015

The objective of this study was to investigate the toxicological information of freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food ingredient. The powder, suspended in distilled water, was administered once daily by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0 (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated administration, the standard toxicological parameters such as mortality, clinical signs, body weight, food consumption, ophthalmologic examination, clinical pathology, organ weights and macro/microscopic examination were applied for assessment of general toxicity. In addition, serum IgE and histamine levels were determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma larvae did not produce treatment-related changes or findings in any toxicological parameters in either sex of any dosed groups except for slight increases in serum histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a candidate to be edible material.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.143-144
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• 2001

Eukaryotic nuclear transcription factor, NF-B and cyclooxygenase-2 (COX-2) has been implicated in pathogenesis of many human diseases including tumor and are known to be activated by various external stimuli. Recently, increasing evidences have supported that L-ascorbic acid (LAA) is selectively toxic to some types of tumors at pharmacological concentrations as a prooxidant, rather than antioxidant.(omitted)

• Toxicological Research
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• 제6권2호
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• pp.159-166
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• 1990

The ability of many toxigenic fungi to invade and develop in a wide variety of raw ingredients of human diet renders human exposure to mycotoxing very difficult to avoid. Most of the energy-rich commodities, such as cereal grains, oil seeds, tree nuts, and dehydrated fruits, are susceptible to mycotoxin contamination. Mycotoxins therefare have been recognized as an important class of hazardous substances in the human food chain. Although human exposure to mycotoxins is largely through ingestion, inhalation and skin contact may also be significant under conditions other than consumption of foods. Human ingestion of mycotoxins is due to consumption of contaminated dietary ingredients and the edible tissues and products of domestic animals that have been exposed to mycotoxins in moldy feed. Large scale acute human mycotoxicoses, such as ergotism in France, alimentary toxic aleukia in Russia, yellow rice syndrome in Japan, endemic nephropathy in Balkan countries, and acute aflatoxin poisonings in India and Taiwan, have been well documented, indicating that mycotoxicosis is a global problem. In some incidents, hundreds of victims were killed and many more became seriously ill. The mycotoxins that have been implicated in the etiology of these human diseases include aflatoxins, citreoviridin, cyclopiazonic acid, ergot alkaloids, moniliformin, ochratoxin A, trichothecenes, tenuazonic acid, and zearalenone. Among these, aflatoxins have been also implicated in the etiology of human primary liver cancer in those high-incidence countries in Africa and southeast Asia. It is well recognized that cause-effect relationship between mycotoxins and human diseases is very difficult to establish, especially for the cancer connection. Careful risk assessment must be performed to determine whether a mycotoxin indeed warrants costly regulatory actions.

• Toxicological Research
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• 제17권3호
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• pp.203-213
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• 2001

We investigated the toxic effects of propylthiouracil (PTU) In Sprague-Dawley (SD) rats to develop and validate an enhanced Protocol for Test Guideline 407 as OECD Project. Twenty male and female SD rats,7 weeks old, were treated with PTU in corn oil at levels of 0, 0.1, 1 and 10 mg/kg/day for 4 weeks orally. Clinical observation, body weight changes, food uptake, water consumption, urinalysis, estrus cycle and sperm analysis, serum chemist교, autopsy findings and histopathological findings were evaluated in this study. No clinical signs and mortality were observed in the study. The body weights and food uptakes in the group treated with 10 mg/kg/day were reduced from 3 weeks after the initiation of the treatment. The levels of 3,5,3'-triiodothyronine (T3) and thyroxine (T4, 3,5,3',5'-tetraiodothyrosine) were also significantly decreased in the group treated with 10 mg/kg/day. Also, the relative and absolute organ weights of thymuses were decreased. Thyroid glands of rats in the group treated with PTU 10 mg/kg/day were bigger than those of rats in the control group. In the histopathological examination, diffuse hyperplasia and hypertrophy of thyroid follicular cells were observed in all treatment groups, leading to the reduction of lumen size and papillary enfolding of lining epithelium. The degree of lesion was increased in a dose-dependent manner. The results suggested that PTU would cause toxicity in thyroid gland and decrease the levels of T3 and T4 in SD rats. However there were no effects on the other organ including testis and uterus especially in spermatogenesis and estrus cycle. On the basis of the results, enhanced protocol for Test Guideline (TG) 407 may be sensitive and reliable to detect endocrine-active substances like PTU.

• Toxicological Research
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• 제33권2호
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• pp.165-171
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• 2017

Bisphenol A (BPA) is a monomer used in a polymerization reaction in the production of polycarbonate plastics. It has been used in many consumer products, including plastics, polyvinyl chloride, food packaging, dental sealants, and thermal receipts. However, there is little information available on the inhalation toxicity of BPA. Therefore, the aim of this study was to determine its inhalation toxicity and effects on the estrous cycle, spatial learning, and memory. Sprague-Dawley rats were exposed to 0, 10, 30, and $90mg/m^3$ BPA, 6 hr/day, 5 days/week for 8 weeks via whole-body inhalation. Mortality, clinical signs, body weight, hematology, serum chemistry, estrous cycle parameters, performance in the Morris water maze test, and organ weights, as well as gross and histopathological findings, were compared between the control and BPA exposure groups. Statistically significant changes were observed in serum chemistry and organ weights upon exposure to BPA. However, there was no BPA-related toxic effect on the body weight, food consumption, hematology, serum chemistry, organ weights, estrous cycle, performance in the Morris water maze test, or gross or histopathological lesions in any male or female rats in the BPA exposure groups. In conclusion, the results of this study suggested that the no observable adverse effect level (NOAEL) for BPA in rats is above $90mg/m^3$/6 hr/day, 5 days/week upon 8-week exposure. Furthermore, BPA did not affect the estrous cycle, spatial learning, or memory in rats.

• Toxicological Research
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• 제27권4호
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• pp.247-251
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• 2011

To clarify whether inhibitory effect of estrogen on liver tumor is associated with cell proliferation, we investigated its role in diethylnitrosamine (DEN)-induced rat preneoplastic lesions, with time sequenced manners. F344 male rats (n = 90) were divided into three groups at 5 weeks of age. The mini-osmotic pumps providing a continuous infusion of DEN was implanted into the abdominal cavity of each animal in group 1, 2 and 3 at 6 weeks of age. To see the effect of estrogen, pellet containing 1 or 10 ${\mu}g$ of estradiol-3-benzoate (EB) was implanted subcutaneously in the animals of groups 2 or 3, respectively, one week prior to DEN treatment. Ten animals of each group were euthanized at 10, 14 and 18 weeks after DEN treatment. Liver tissues at each time point were fixed in 10% phosphate-buffered formalin and were processed and embedded in paraffin and 5 ${\mu}g$ sections mounted on a silanized slide. Glutathione S-transferase placental form (GST-P) positive foci and 5-bromo-2-deoxyuridine (BrdU) labeling cells were detected at each time point. Area of GST-P positive foci in DEN+EB 1 or 10 ${\mu}g$ group was significantly decreased compared to DEN alone at 14 weeks (p < 0.01 or p < 0.05, respectively) an at 18 weeks (p < 0.05 or p < 0.01, respectively). BrdU index in DEN+EB 1 or 10 ${\mu}g$ groups was significantly decreased compared to DEN alone at 14 weeks and at 18 weeks (p < 0.01). Taken together, we conclude that EB treatment decrease the DEN-induced liver preneoplastic lesions and this may be associated with decrease of cellular proliferation.

• Toxicological Research
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• 제25권1호
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• pp.23-28
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• 2009

Some of the edible plants like apricot kernel, flaxseed, and cassava generate hydrogen cyanide (HCN) when cyanogenic glycosides are hydrolyzed. Rhodanese (thiosulfate: cyanide sulfurtransferases of TSTs; EC: 2.8.1.1) is a sulfide-detoxifying enzymes that converts cyanides into thiocyanate and sulfite. This enzyme exists in a liver and kidneys in abundance. The present study is to evaluate the conversion of apricot cyanogenic glycosides into thiocyanate by human hepatic (HepG2) and colonal (HT-29) cells, and the induction of the enzymes in the rat. The effects of short term exposure of amygdalin to rats have also been investigated. Cytosolic, mitochondrial, and microsomal fractions from HepG2 and HT-29 cells and normal male Spraque-Dawley rats were used. When apricot kernel extract was used as substrate, the rhodanese activity in liver cells was higher than the activity in colon cells, both from established human cell line or animal tissue. The cytosolic fractions showed the highest rhodanese activity in all of the cells, exhibiting two to three times that of microsomal fractions. Moreover, the cell homogenates could metabolize apricot extract to thiocyanate suggesting cellular hydrolysis of cyanogenic glycoside to cyanide ion, followed by a sulfur transfer to thiocyanate. After the consumption of amygdalin for 14 days, growth of rats began to decrease relative to that of the control group though a significant change in thyroid has not been observed. The resulting data support the conversion to thiocyanate, which relate to the thyroid dysfunction caused by the chronic dietary intake of cyanide. Because Korean eats a lot of Brassicaceae vegetables such as Chinese cabbage and radish, the results of this study might indicate the involvement of rhodanese in prolonged exposure of cyanogenic glycosides.

• Toxicological Research
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• 제33권4호
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• pp.333-342
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• 2017

Ethyl formate, a volatile solvent, has insecticidal and fungicidal properties and is suggested as a potential fumigant for stored crop and fruit. Its primary contact route is through the respiratory tract; however, reliable repeated toxicological studies focusing on the inhalation route have not been published to date. Therefore, the present study was conducted to investigate the safety of a 90-day repeated inhalation exposure in rats. Forty male and 40 female rats were exposed to ethyl formate vapor via inhalation at concentrations of 0, 66, 330, and 1,320 ppm for 6 hr/day, 5 days a week for 13 weeks. Clinical signs, body weights, food consumption, urinalysis, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathological findings were compared between the control and ethyl formate-exposed groups. Locomotor activity decreased during exposure and recovered afterward in male and female rats exposed to 1,320 ppm ethyl formate. Body weight and food consumption continuously decreased in both sexes exposed to 1,320 ppm ethyl formate from week 1 or 3 compared with the control values. The increases in adrenal weight and decreases in thymus weight were noted in both sexes exposed to ethyl formate at 1,320 ppm. Degeneration, squamous metaplasia of olfactory epithelium in the nasopharyngeal tissue, or both were noted in the male and female rats at 1,320 ppm and female rats at 330 ppm ethyl formate. Taken together, our results indicate that ethyl formate-induced changes were not observed in male and female rats at 330 and 66 ppm, respectively. This indicates that exposure to ethyl formate at concentrations below 66 ppm for 90 days is relatively safe in rats. This is the first report of a full-scale repeated inhalation toxicity assessment in rats and could contribute to controlling occupational environmental hazards related to ethyl formate.