• 한국대기환경학회지
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• 제22권2호
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• pp.201-208
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• 2006

Several carbonyl compounds are important because of their irritant and toxic properties, mutagenicity and carcinogenicity. Therefore, they are regulated in korean odor emission standard. In this study, atmospheric pressure ionization-mass spectrometry(API-MS) is used for the analysis of carbonyl compounds after derivatization with 2, 4-dinitrophenylhydrazine (DNPH) and liquid chromatographic separation. In the negative ion mode, the $[M-H]^-$ pseudomolecular ions are most abundant for the carbonyls. Analytical parameters such as linearity, repeatability and minimum detection limit were evaluated. The linearities ($r^2$) for carbonyls were $0.9977{\sim}0.9999$ when analyte concentration ranges from $25\;to\;250{\mu}g/L$(n=6). The relative standard deviations (%RSD) for carbonyls were $0.55{\sim}3.51%$ for concentration of $100{\mu}g/L$(n=5). The minimum detection limit (MDL) was $1.88{\mu}g/L$(0.27 ppb) for i-valeraldehyde. It was shown that LC-MS method has a great potential for carbonyl compounds analysis.

• 생약학회지
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• 제49권3호
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• pp.246-254
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• 2018

Pectin lyase-modified red ginseng extract (GS-E3D) is a newly developed ginsenoside Rd-enriched ginseng extract. This study was designed to investigate the skin safety of GS-E3D. Single oral toxicity, single dermal toxicity, bovine corneal opacity and permeability (BCOP) assay, skin irritation test with $SkinEthic^{TM}$ human epidermis model, skin sensitization local lymph node assay, and human patch test, were examined. The oral and dermal $LD_{50}$ value of GS-E3D was over 2,000 mg/kg in rats. GS-E3D was identified as a non-irritant to skin in BCOP assay, human epidermis models, and patch test from the 32 human subjects. The skin sensitization potential of GS-E3D was less than 25% in local lymph node assay. These results indicate that GS-E3D can be used as a safe ingredient without adverse effects in various skin care products.

• 환경위생공학
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• 제21권1호
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• pp.35-43
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• 2006

Formaldehyde is important because of their irritant and toxic properties, mutagenicity and carcinogenicity. In this study, liquid chromatography-mass spectrometry (LC-MS) is used for the analysis of formaldehyde after derivatization with 2,4-dinitrophenylhydrazine (DNPH) cartridge. Analytical parameters such as linearity, repeatability and minimum detection limit were evaluated. The linearity ($r^2$) was 0.9997 when analyte concentration ranges from 25 to $200{\mu}g/l$. The relative standard deviation (%RSD) was 1.25 % for concentration of $200{\mu}g/l$. The minimum detection limit (MDL) was 0.73 ppbv. It was shown that LC-MS method has a great potential for formaldehyde analysis. The results of formaldehyde from the survey of Ban-Woll and Shi-Hwa Industrial Complex samples, the highest level was 6.20, 3.93 ppb, respectively. The highest emission level of formaldehyde at chemical plants in the Ban-Woll' Shi-Hwa Industrial Complex was 5421.25 ppb.

• Preventive Nutrition and Food Science
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• 제17권1호
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• pp.14-21
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• 2012

The purpose of this study was to investigate the anti-allergy activities of persimmon leaf extract (PLE) on a phthalic anhydride (PA)-induced allergic mouse model. A human leukemic mast cell line (HMC-1) was used to examine the inhibitory activity of PLE on the histamine release by human leukemic mast cells. PLE inhibited histamine release from HMC-1 cells in response to cross-linkage of high-affinity IgE receptor-${\alpha}$ ($Fc{\varepsilon}RI{\alpha}$). Additionally, a PA-induced allergic mouse model was used to investigate the effects of PLE in vivo. Mice were orally administrated with or without PLE of single dose (250 mg/kg/day) for 31 days. Oral intake of PLE significantly inhibited passive cutaneous reactions. Oral administration of PLE to PA-induced allergic mice also led to a striking suppression of the development of contact dermatitis, ear swelling and lymph node weight. In addition, PA-specific IL-4 production of draining lymph node cells was markedly diminished by PLE oral administration, but not IFN-${\gamma}$. Furthermore, PLE treatment suppressed PA-induced thymus and activation-regulated chemokine (CCL17) and cutaneous T cell-attracting chemokine (CCL27) expressions in ear tissues. Based on these results, we suggest that PLE may have therapeutic potential as an effective material for management of irritant contact dermatitis or related inflammatory diseases.

• 약학회지
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• 제40권2호
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• pp.155-162
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• 1996

Hyperkeratinization is a dermatologic disorder, which is due to the increase of corneocyte cohesion force. Glycolic acid, an alpha hydroxy acid(AHA), has been used to breakdown the hyperkeratinization processes. However, it has a problem of skin irritation when applied topically, due to the strong acidity especially in high concentration. A molecular optimization of glycolic acid has been tried to reduce the skin irritation by the way of prodrug formation. Ethyl glycolate was synthesized by the esterification of glycolic acid with ethanol in acidic conditions in the presence of sulfuric acid, and examined under the spectroscopic trials, such as UV, IR, $^1H$-NMR, and GC-MS. The physicochemical and biopharmaceutical properties of the prodrug were also evaluated. Through the toxicological tests of both skin irritation and eye mucous irritation, it has been proved that ethyl glycolate was less irritant than glycolic acid, since the pH value of synthetic prodrug was higher than that of glycolic acid. In the penetration test through nude mouse skin by diffusion cell, ethyl glycolate was continuously hydrolyzed to glycolic acid, which was assayed form the receptor compartment. It was obtained that the penetrated amount of ethyl glycolate was five times higher than that of glycolic acid. These results suggest that ethyl glycolate might be a successful prodrug of glycolic acid to reduce the skin irritation and to increase the skin penetration as well.

• Biomolecules & Therapeutics
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• 제26권4호
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• pp.417-423
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• 2018

Extracellular interleukin 1 alpha (IL-$1{\alpha}$) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-$1{\alpha}$ is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals. This study examined whether and how IL-1ra, particularly extracellularly released IL-1ra, was involved in chemically-induced keratinocyte cytotoxicity and skin irritation. Primary cultured normal adult skin keratinocytes were treated with cytotoxic doses of chemicals (hydroquinone, retinoic acid, sodium lauryl sulfate, or urshiol) with or without recombinant IL-1ra treatment. Mouse skin was administered irritant concentrations of hydroquinone or retinoic acid. IL-1ra (mRNA and/or intracellular/extracellularly released protein) levels increased in the chemically treated cultured keratinocytes with IL-$1{\alpha}$ and IL-$1{\beta}$ mRNAs and in the chemically exposed epidermis of the mouse skin. Recombinant IL-1ra treatment significantly reduced the chemically-induced apoptotic death and intracellular/extracellularly released IL-$1{\alpha}$ and IL-$1{\beta}$ in keratinocytes. Collectively, extracellular IL-1ra released from keratinocytes could be a compensatory mechanism to reduce the chemically-induced keratinocyte apoptosis by antagonism to IL-$1{\alpha}$ and IL-$1{\beta}$, suggesting potential applications to predict skin irritation.

• Toxicological Research
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• 제19권2호
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• pp.133-139
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• 2003

Allergic contact dermatitis may be caused by a wide variety of chemicals. A murine local lymph node assay (LLNA) has been developed as an alternative to guinea pig models for assessing the contact sensitization potential of chemical. However, there is a need to develop a nonradioisotopic endpoint for the LLNA, because of the radioisotopic method's requiring the use of special facilities. In this study, we investigated the development of a nonradioisotopic endpoint for LLNA using ELISA (enzyme-linked immunosorbent assay). Female Balb/c mice were treated by the topical application on the dorsum of both ears with four different strong sensitizers, 2,4-dinitrochlorobenzene (DNCB), oxazolone (OXZ), toluene diisocyanate (TDI), and trimellitic anhydride (TMA), and a strong irritant, sodium lauryl sulfate (SLS), once daily for three consecutive days. The proliferation of cells in the auricular Iymph node was analyzed by means of the labelling index (Ll) of bromodeoxyuridine (BrdU) incorporation into cells. The weights of the Iymph nodes in the mice treated with allergens, DNCB, OXZ, TDl and TMA were increased compared to the vehicle control. The stimulation index (Sl) of mice treated with DNCB, OXZ, TDl, and TMA was over three-fold increase compared to the vehicle control. However, the S1 of mice exposed to SLS was not significantly increased compared to the vehicle control, while the lymph node weight of SLS was significantly increased. These results suggest that the LLNA modified endpoint using ELISA based on BrdU incorporation could provide a useful method of screening for irritants and allergens.

• Toxicological Research
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• 제31권1호
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• pp.49-59
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• 2015

Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers ($IL-1{\alpha}$, $IL-1{\beta}$, IL-8 and $TNF-{\alpha}$) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.

• 한국안광학회지
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• 제10권4호
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• pp.293-304
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• 2005

렌즈 세척제인 ReNu$^{TM}$의 안자극테스트를 한국식품의약품안전청의 고시에 따라서 Draize방법(1959)을 사용하여 분석하였다. 부가해서 검사 항목의 잠재성 독성테스트를 위해서 염증세포와 비염증세포의 비율에서 역시 눈 분비물에 대한 세포도말표본사용으로 관찰하였다. 검사에서 각막, 홍채, 망막, 그리고 공막에 대한 조직학적 변화들은 역시 모든 실험동물에서 관찰되었다. 각막과 결막의 약간 자극성은 벼비척그룹에서 점안후 1, 2, 3일에서 관찰되었다. 이러한 지점에서의 안점막자극지수(MIOI)는 각각 4.17, 3.00, 1.33으로 확인되었다. 세척군에서 각막과 결막의 약간의 자극은 각각 0.67과 1.33으로서 MIOI로서 점안후 1일과 2일에서 관찰되었다. 따라서 ReNu$^{TM}$은 비자극성 물질로 생각된다. 왜냐하면 MIOI는 세척군과 비세척군 모두에서 전체 실험기간을 통해서 5.00이하로 관찰되었다. 급성안자극계수(IAOI)는 역시 4.17로서 확인되었다(점안후 일일). 일부의 예외들은 비세척군의 점안후 1일에서 분비물에서 염증세포 비율의 경향이 증가되었다. 그러나 유의성은 없었다. 한편 안분비물의 도말세포관찰에서 의미있는 변화들은 본 연구에서 관찰되었다. 부가해서 각막, 홍채, 공막 위에서 비정상조직 변화는 역시 비처리된 대군군 눈과 비교해서 ReNu$^{TM}$, 점안군에서는 탐지되지 않았다.

• 한국안광학회지
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• 제12권2호
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• pp.67-78
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• 2007

시판중인 렌즈 보존액 중 가장 흔히 사용 또는 유통되고 있는 CLIWELL$^{TM}$에 대한 안점막자극성 시험을 식품의약품 안전청 고시에 따라 Draize법을 이용하여 그 자극성의 정도를 평가하고, 눈에 가해질 수 있는 잠재적인 독성을 평가하기 위하여, 배출물에 대한 도말표본 상에서 염증세포 및 비 염증성 유상피세포가 차지하는 비율과 함께 점안 14일 후 안구 중, 각막, 홍채, 망막 및 공막의 조직병리학적 관찰을 실시한 결과 다음과 같은 결과를 얻었다. 비 세척군에서는 점안 후 1, 2 및 3일에 국한하여, 각막과 결막에 경미한 자극이 관찰되어, 이 기간 동안의 평균 안점막 자극지수 MIOI가 각각 4.50, 1.67 및 0.67로 관찰되었으며, 세척군에서는 점안 후 1 및 2일에 국한하여, 결막에서 경미한 자극성이 인정되었고, 이때 MIOI는 각각 0.67로 관찰되었다. 따라서 CLIWELL$^{TM}$은 세척군 및 비 세척군 모두에서 MIOI가 모든 관찰 기간에서 4.50이하로 관찰되었으며, IAOI 역시 점안 1일 후 4.50으로 관찰되어 무자극성 물질로 판단되었다. 한편 배출물에 대한 염증성 세포의 비율은 무처치 대조군과 비교하여 점안 1일 후 유의성 있는 염증세포 비율의 증가가 비세척군에 국한하여 인정된 이외에 의미 있는 변화는 인정되지 않았다. 또한 안구의 조직병리학적 검사에서 각막, 홍채, 망막 및 공막 모두에서 무처치 대조군과 비교하여 의미 있는 변화는 인정되지 않았다.