Immunotoxicity of ethyl carbamate in female BALB/c mice : role of esterase and cytochrome P450 esterase와 cytochrome P450의 역할

Cha, Shin Woo,Gu, Hee Kyoung,Lee, Ki Poong,Lee, Mun Han,Han, Sang Seop,Jeong, Tae Cheon 영남대학교 약품개발연구소 2000 영남대학교 약품개발연구소 연구업적집 Vol.10 No.-

Ethyl carbamate, a potent carcinogen, has been characterized to be metabolized by cytochrome P450(P450) and esterase. It has recently been demonstrated that P450 may activate ethyl carbamate to immunotoxic metabolites. To investigate the role of esterase in ethyl carbamate-induced immunosuppression, mice were pretreated intraperitoneally with an esterase inhibitor, diazinon, at 20 ㎎/㎏ 30min prior to the administration of ethyl carbamate intraperi-toneally at 100 and 400㎎/㎏ for 7 consecutive days. Pretreatment with diazinon completely blocked the serum esterase activity. Histopathologically splenic and thymic atrophy was observed when mice were treated with ethyl carbamate, which was potentiated by he pretreatment with diazinon. In spleen, lymphocytes in the periarteriolar lymphoid sheath and the marginal zone appeared to be depleted in the white pulps. In thymus, ethyl carbamate caused a marked depletion of cells in cortex. The antibody response to sheep red blood cells(SRBCs) was more suppressed by ethyl carbamate in diazinon-pretreated groups. These results suggest that the metabolism of ethyl carbamate by esterase may be an inactivation pathway in ethyl carbamate-induced immunosuppression. In addition, ethyl N-hydroxycarbamate, a P450 metabolite, suppressed the lymphoproliferative response induced by lipopolysaccharide and concanavalin A in splenocyte cultures. These results indicate that the metabolism of ethyl carbamate by P450 may be an activation pathway in immunosuppression by ethyl carbamate. ⓒ 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.

매실주 숙성 중 매실부위, 알콜농도 및 trans-Resveratrol 이 에틸카바메이트 생성에 미치는 영향

황래홍,김애경,박경애,김지영,황인숙,채영주 한국식품위생안전성학회 2009 한국식품위생안전성학회지 Vol.24 No.3

The effects of part of plum, alcohol content and addition of t-resveratrol on the formation of ethyl carbamate during the fermentation for wine were investigated at a time interval (45 days) for 6 months. The concentration of the ethyl carbamate in plum wine was determined according to KFDA guideline for ethyl carbamate analysis. In the plum wine with 16% or 30% alcohol content, the concentrations of ethyl carbamate were increased with time of fermentation periods. The maximum concentrations of ethyl carbamate in 16% and 30% plum wines after the fermentation for 6 months were 0.071 μg/g and 0.188 μg/g, respectively. When t-resveratrol was added at the level of 10 μg/g in both 16% and 30% plum wine, the concentrations of ethyl carbamate at 6 months were 0.078 and 0.216 μg/ g, respectively. The addition of t-resveratrol at the level of 300 μg/g in both 16% or 30% plum wine, the concentrations of ethyl carbamate at 6 months were 0.078 and 0.169 μg/g, respectively. The ethyl carbamate in the plum wine was not formed during fermentation for 6 month as using the flesh of plum, but 0.588 μg/g of ethyl carbamate was formed as using plum with plum seed. The addition of 300 μg/g of t-resveratrol actually increased the concentration of the ethyl carbamate by 0.088 μg/g as fermented for 6 months using plum with seed. These results suggest that the flesh of plum should be used to reduce the formation of ethylcarbamate for production of plum wine and that the addition of t-resveratrol during fermentation of plum wine can not reduce the concentration of the ethyl carbamate.

[연구노트] Ethyl carbamate 전구체인 N-carbamyl 화합물과 에탄올의 반응에 대한 NaCl의 영향

고은미(Eunmi Koh),권훈정(Hoonjeong Kwon) 한국식품과학회 2007 한국식품과학회지 Vol.39 No.1

발효식품에 다량 함유되어 있는 NaCl이 ethyl carbamate 전구체인 N-carbamyl 화합물과 에탄올과의 화학반응에 영향을 주는 것으로 확인되었다. N-carbamyl 화합물과 에탄올의 화학반응 속도를 비교한 결과, carbamyl phosphate, urea, 시트룰린 순서로 ethyl carbamate의 생성 속도가 감소되었다. 또한 NaCl은 ethyl carbamate의 주요한 전구체로 추정되는 carbamyl phosphate 또는 시트룰린과 에탄올의 화학반응을 억제한 반면에, urea와 에탄올과의 반응은 오히려 촉진하였다. 앞으로 발효식품에서 ethyl carbamate 및 그 전구체의 생화학적 생성 기전뿐만 아니라 전구체간의 화학반응에 대한 NaCl의 역할에 대한 연구가 지속되어야 할 것으로 사료된다. Ethyl carbamate, which is also known as a possible human carcinogen, is formed by ethanolysis of N-carbamyl compounds such as carbamyl phosphate, urea, or citrulline. NaCI that is highly present in fermented foods was suspected to have an influence on ethyl carbamate formation. This study was designed to determine the effect of NaCI on the chemical reactions upon incubation of ethanol with the N-carbamyl compound in a 25% NaCI solution or in the absence of NaCI, and to find a possible association with the formation of ethyl carbamate. While the amount of ethyl carbamate formed in a urea solution with the addition of NaCI was increased up to 26%, the amount formed with citrulline or carbamyl phosphate in the presence of NaCI was decreased up to 30% and 40%, respectively. This indicates that NaCI should be considered as a potential factor influencing the rate of ethyl carbamate formation from its precursors.

Determination of ethyl carbamate in soy sauce from Korean market

Choi, Bogyoung,Jang, Youngbin,Koh, Eunmi Elsevier 2018 Food control Vol.93 No.-

<P><B>Abstract</B></P> <P>This study was conducted to monitor the concentration of ethyl carbamate in three different types of soy sauce commercially available in Korea. A total of 90 soy sauces, including 35 fermented, 44 mixed and 11 traditional products, were collected and analysed for ethyl carbamate using a gas chromatograph-mass spectrometer. The concentrations of ethyl carbamate ranged from not-detected to 73.2 μg/kg with a mean value of 7.4 μg/kg. The proportion of positive samples was about twice as high in fermented soy sauce (57%) compared to mixed (25%) and traditional (27%) products. The estimated mean and 95th percentile exposure to ethyl carbamate from soy sauce were 0.80 and 2.82 ng/kg body weight (bw) per day, respectively. Using the benchmark dose lower confidence limit 10% (BMDL<SUB>10</SUB>) of 0.3 mg/kg bw per day, the margins of exposure (MOEs) were 374,000 for mean exposure and 106,000 for 95th percentile exposure. These results indicate that exposure to ethyl carbamate from soy sauce in the Korean population is unlikely to be of health concern.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A total of 90 soy sauces from Korean market were analysed for ethyl carbamate. </LI> <LI> The concentrations of ethyl carbamate ranged from not-detected from 73.2 μg/kg. </LI> <LI> Estimated daily mean and 95th intake of ethyl carbamate were 0.79 and 2.79 ng/kg bw. </LI> <LI> Exposure to ethyl carbamate from soy sauce in Koreans is unlikely to be of concern. </LI> </UL> </P>

Ethyl Carbamate의 그 대산 산물의 피부종양 유발에 관한 비교 연구

안성구,김수정,원진형,최응호,홍성노 연세대학교 원주의과대학 1995 원주의대논문집 Vol.8 No.1

Role of corticosterone in ethyl carbamate-induced immunosuppression in female BALB/c mice

Cha, Shin Woo,Lee, Hu Jang,Cho, Myung Haing,Lee, Mun Han,Koh, Woo Suk,Han, Sang-Seop,Kim, Jung-Ae,Lee, Eung-Seok,Nam, Doo-Hyun,Jeong, Tae Cheon 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

We have recently demonstrated that the antibody response to the T-cell-dependent antigen, sheep red blood cells(SRBCs), was suppressed by ethyl carbamate in female BALB/c mice. At the same doses, ethyl carbamate decreased in the numbers of splenic macrophages. B cells, total T cells, CD4^(+) T cells and CD8^(+) T cells. In addition, the serum level of corticosterone was increased dose-dependently. To investigate the possible role of corticosterone in ethylcarbamate-induced immunosuppression, the antibody response to SRBCs and the subpopulation changes of splenocytes and thymocytes were determined in naive, sham-operated and adrenalectomized (ADX) female BALB/c mice. When the mice were treated intraperitoneally with 400 mg/kg ethyl carbamate, the antibody response was significantly suppressed by ethyl carbamated in naive and sham-operated mice in accompanying the decrease in spleen and thymus weights and/or the increase in the level of serum corticosterone. Meanwhile, the antibody response was not suppressed by ethyl carbamate in the ADX mice. The splenic numbers of total cells, macrophages B and T cells, and CD4^(+) cells were decreased by ethyl carbamate in naive and sham-operated mice. Meanwhile, each cell number was comparable with control in the ADX mice. The flow cytometric analyses on thymocytes did not show obvious differences as seen in the spleen. Finally, when the ADX mice were treated intraperitoneally with 25 mg/kg corticosterone, the antibody response was significantly suppressed. Taken together, our present results suggested that corticosterone might be, at least partially, responsible for ethy; carbamate-induced immunosuppression in female BALB/c mice. ⓒ 2001 Elsevier Science Ireland Ltd. All rights reserved.

Ethyl Carbamate와 그 대사산물의 피부종양 유발에 관한 조직학적 연구

안성구 ( Sung Ku Ahn ),정준 ( Joon Chung ),박윤기 ( Yoon Kee Park ),박광균 ( Kwang Kyun Park ) 대한피부과학회 1995 大韓皮膚科學會誌 Vol.33 No.4

Background : Ethyl crbmate(EC) has been identified at low microgram quantities in various fermented beverages, destiled products and tobacco smoke. EC has long been known as a carcinogen. Oxidation of the ethyl group of EC is followed by dehydration to yield the carcinogen vinyl carbamate (VC). This is further oxidized to vinyl carbamate epoxide(VCO). VC and VCO proved to be much more carcirogenic than EC. Object: The objective of this study is to compare the potency of carcinogenic ability and histologic changes in skin tumors induced by EC, VC, or VCO. Methods : In this exeriment, the tumor induction was performed by painting the mouse skin once a week for five weeks with EC, VC and VCO solution, and then 12-0-tetradecanoyl-phorbol-13-acetate(TP2) was treated in the same manner twice a week for 35 weeks. We biopsied the skin at B 0, 15, 25, 30 and 35 weeks and stained the specimens with hematoxylineosin. Results : The time period for the first appearance of papilloma was 6 weeks in the VC-TPA and VCO-TPA group, but, 15 weeks in the EC TPA group. The average number of papilloma showed a statistically sign.ficant difference after 15 weeks between the EC-TPA, VC-TPA and VCO-TPA group. The occurrence of keratoacanthoma and squamous cell carcinoma was 16 and 21 weeks respectively. Histologic changes, such as epidermal layers, pseudohorncysts, degree of hyperkeratosis, hypergranulosis, dysplasia and dyskeratotic cells were more prominent in the papil loma than in the non-papilloma lesion. Dermal changes disclosed similiar findings, that is, increased dermal thicknes, proliferation of vessels and hair follicles, and fibrosis of the dermis. Squamous cell carcinomis and keratoacanthomas were produced only in the VCO-TPA group. Conclusion : From the above results it is concluded that VC and VCO have a more potent carcinogenic potential than EC. Various skin tumors, such as papilloma, keratoacanthoma or squamous cell carcinoma were prorduced by the above carcinogens. (Kor J Dermatol 1995;33(4): 599-610)

Effect of fruit thermal processing on ethyl carbamate content in maesil (Prunus mume) liqueur

최보경,고은미 한국식품과학회 2021 Food Science and Biotechnology Vol.30 No.11

The thermal effect of maesil on the content ofethyl carbamate and its precursors during one-year ripeningof maesil liqueur was investigated. Fresh maesil (control),fruit blanched for 2 min (blanched), and fruit blanched anddried for 15 h at 50 C (blanched/dried) were soaked in theliquor containing 25% alcohol at a ratio of 1:2 (w/w) for100 days at 25 C and the liquid was further ripened for260 days. Ethyl carbamate ranged from 13.1 to 204.4 lg/kg with the highest value at 210 day. Thermally treatedsamples had higher ethyl carbamate concentration than thecontrol, suggesting that thermal treatment increased theformation of ethyl carbamate. A positive correlationbetween ethyl carbamate content and b-glucosidase activityin all samples indicated that enzymatic hydrolysis ofamygdalin by b-glucosidase determined ethyl carbamateconcentration during the fermentation of maesil liqueur.

GC/MS를 이용한 한국 주류 중의 Ethyl Carbamate정량

박교범,이석근 한국분석과학회 2002 분석과학 Vol.15 No.1

한국 고유의 전통주 및 일반 알코올 음료에 대한 ethyl carbamate의 함량을 알아보기 위하여 국내에서 시판되고 있는 술을 dichloromethane용매로 추출한 후 GC/MS-SIM방법에 의해 분석하였다. 분석결과 ethyl carbamate는 한국고유의 전통주에 4.6-50.2 ㎍/L, 비 증류주에 27.8-45.4 ㎍/L, 위스키에는 24.8-55.1 ㎍/L함유되어 있음을 알 수 있었다. 회수율은 83.3-104.8 %의 값을 얻었고, 상대 표준편차는 1.8-14.81 %, 검출한계는 0.3 ㎍/L이었다.

5,7-Dibromoto-8-hydroxyquinaldyl-N-ethylcarbamate의 합성 및 항균작용에 관한 연구

姜會洋,丁讚 대한보건협회 1998 대한보건연구 Vol.24 No.1

殺蟲作用, 殺蟲效果, 抗菌力, 抗菌作用이 강력하고 低毒性인 새로운 抗微生物劑를 개발할 목적으로 quinoline 고리를 가지는 새로운 carbamate系 化合物인 5,7-dibromo-8-hydroxyquinaldyl-N-ethylcarbamate를 4가지 방법(A,B,C,D법)으로 合成하였다. A법: 非水溶媒에 溶解한후 觸媒로서 triethylamine을 反應物質과 同 mole 比率로 첨가하고 ethyl isocyanate를 反應物質의 1.5mole 比率로 加하여 反應시키는 方法. B법: A법에서 觸媒를 사용하지 않는 方法. C법: A법에서 ethyl isocyanate 대신에 ethyl carbamoyl chloride를 1.5mole 比率로 反應 시키는 方法. D법: C법에서 觸媒를 사용하지 않는 方法. 各 合成法에 따른 生成物의 收率은 carbamoyl chloride를 作用시키는 縮合反應이 ethyl isocyanate를 作用시키는 添加反應보다 不良하였다. 觸媒存在下에 添加反應(C법)과 縮合反應(C법)을 비교하면 C법이 A법보다 18% 收率이 不良하고, 觸媒를 사용하지 않은 添加反應(B법)과 縮合反應(D법)을 비교하면 D법이 B법보다 25% 수율이 低下되었다. 또한 觸媒存在下의 添加反應(A법)에서는 無觸媒下의 添加反憊(B법)보다 6% 정도 收率이 높았다. 5,7-Dibromo-8-hydroxyquinaldyl-N-ethylcarbamate, one of the carbamate derivatives which is generally used as insecticides, was newly synthesized. Its physical properities were determined and chemical structure was indentified by means of i.r., nmr in addition to elemental analysis. The yield of addition, using triethylamine as catalyst, 5,7-dibromo-8-hydroxyquinaldine and isocyanate was better than that of condensation of 5,7-dibromo-8-hydroxyquinaldine with carbamoylchloride. The effect of the compound on rabbit's ileum, and antibacterial activity against Staphylococcus aureus, Salmonella typhi, Escherichia coli, and Pseudomonas aeruginosa were examined. It was observed that the dosage over 250㎍/㎖ of the compound relaxed rabbit's ileum and the same dosage of the compound inhibited growth of the above strains of bactera.