Kim, Yong-Soon
(Chronic Inhalation Toxicity Research Center, Chemicals Toxicity Research Bureau, Occupational Safety and Health Research Institute, KOSHA)
,
Lee, Sung-Bae
(Chronic Inhalation Toxicity Research Center, Chemicals Toxicity Research Bureau, Occupational Safety and Health Research Institute, KOSHA)
,
Lim, Cheol-Hong
(Chronic Inhalation Toxicity Research Center, Chemicals Toxicity Research Bureau, Occupational Safety and Health Research Institute, KOSHA)
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...
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 $0.11mg/m^3$.
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 $0.11mg/m^3$.
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제안 방법
Body weight and food consumption were measured once per week. Activity was measured during the final exposure week using an activity monitoring system (Sibata Co. Ltd.) and lung function was measured using a non-invasive, unrestrained plethysmographic (PLY 3123, Buxco, Wilmington, NC, USA) at 3-day, 4-week, and 12-week durations after exposure.
DDAC aerosols in the chamber were sampled with a XAD2 resin tube (8 × 110 mm, 200/400 mg XAD-2, SKC, PA, USA) and measured with an ion chromatography (Dionex AS50, CA, USA) equipped with an electron capture detector (Agilent 1049A, Waldbronn, Germany).
The study administered 150 µg/kg of DDAC via intratracheal instillation and discovered pulmonary damage in mice.
대상 데이터
Louis, MO, USA) ad libitum. The animals were divided into four categories of 10 rats for each gender. The categories were the control, low (0.
데이터처리
Data was analyzed based on the Dunnett’s t-test to determine the differences between the control group and the group exposed to DDAC using the commercial program SigmaPlot 12 (Systat Software Inc., San Jose, CA, USA).
성능/효과
(1) reported that exposure to 1,500 µg/kg of DDAC through intratracheal instillation caused severe morbidity with pulmonary congestive edema and that exposure to 150 µg/kg of DDAC caused pulmonary injury whereas exposure to 15 µg/kg of DDAC did not show any visible change in mice. From this report, it can be suggested that DDAC might be approximately 300 times more toxic when administered intratracheally rather than orally. Therefore, we expected that DDAC might also cause severe lung damage when inhaled via the respiratory system.
) were examined through a general repeated toxicity test evaluation, but it was confirmed that there was no dependency on dosage or on test substance. In conclusion, the main factors influencing DDAC inhalation exposure were confirmed to be changes in body weight lung weight, and based on this it is considered that the NOAEL for DDAC is 0.11 mg/m3 for 13 weeks of repeated inhalation exposure.
It was also confirmed that the mean body weight of male rats in the high (1.41 ± 0.71 mg/m3) group was approximately 35% lower than that of the control and the body weight of female rats in the high (1.41 ± 0.71 mg/m3) group was 15% lower than that of the control group (Fig. 2).
Other than the change in body weight, the effects of DDAC were confirmed to be relatively minimal and mild. No significant differences were found in the activity levels and respiratory functions of the rats (Fig.
6 mg/m3 of DDAC was exposed to the rats for 2 weeks to confirm the toxicity of DDAC on rat lungs in a previous study. The main changes observes in this research were the changes in body weight and in the lungs and based on these observations the no observed adverse effect level (NOAEL) for DDAC was suggested to be 0.15 mg/m3. However, the effects were confirmed to be relatively mild, and severe symptoms such as proteinosis and/or fibrosis were not identified (7).
참고문헌 (13)
1 Ohnuma A Yoshida T Tajima H Fukuyama T Hayashi K Yamaguchi S Ohtsuka R Sasaki J Fukumori J Tomita M Kojima S Takahashi N Takeuchi Y Kuwahara M Takeda M Kosaka T Nakashima N Harada T 2010 Didecylmethylammonium chloride induces pulmonary inflammation and fibrosis in mice Exp Toxicol Pathol 62 643 651 10.1016/j.etp.2009.08.007 19762220
2 United States Environmental Protection Agency 2006 Reregistration Eligibility Decision for Aliphatic Alkyl Quaternaries (DDAC), EPA739-R-06-008 United States Environmental Protection Agency Washington, D.C
3 Kim KW Ahn K Yang HJ Lee S Park JD Kim WK Kim JT Kim HH Rha YH Park YM Sohn MH Oh JW Lee HR Lim DH Choung JT Han MY Lee E Kim HY Seo JH Kim BJ Cho YA Do KH Kim SA Jang SJ Lee MS Kim HJ Kwon GY Park JH Gwack J Youn SK Kwon JW Jun BY Pyun BY Hong SJ 2014 Humidifier disinfectant associated children’s interstitial lung disease Am J Respir Crit Care Med 189 48 56 24199596
4 Yang HJ Kim HJ Yu J Lee E Jung YH Kim HY Seo JH Kwon GY Park JH Gwack J Youn SK Kwon JW Jun BY Kim KW Ahn K Lee SY Park JD Kwon JW Kim BJ Lee MS Do KH Jang SJ Pyun BY Hong SJ 2013 Inhalation toxicity of humidifier disinfectants as a risk factor of children’s interstitial lung disease in Korea: a case-control study PLoS ONE 8 e64430 10.1371/journal.pone.0064430 23755124
5 Wikipedia 2014 Biocide [cited 2014 Apr 11]. Available from: http://en.wikipedia.org/wiki/Biocide/
6 United State Environmental Protection Agency 2006 Draft Didecyl Dimethly Ammonium Chloride (DDAC) Risk Assessment Office of Pesticide Programs Antimicrobials Division Arlington, V.A. 9 32
7 Lim CH Chung YH 2014 Effects of Didecyldimethylammonium chloride on sprague-dawley rats after two weeks of inhalation exposure Toxicol Res 30 205 210 10.5487/TR.2014.30.3.205 4206748 --> 25343015
8 Yang JS Choi SB Park SY Lee SB 2012 Analysis of didecyldimethylammonium chloride (DDAC) aerosol in inhalation chamber Anal Sci Technol 25 307 312 10.5806/AST.2012.25.5.307
9 Gomi M Osaki Y Mori M Sakagami Y 2012 Synergistic bacterial effects of a sublethal concentration of didecyldimethylammonium chloride (DDAC) and low concentrations of nonionic surfactants against Staphylococcus aureus Biocontrol Sci 17 175 181 10.4265/bio.17.175 23269219
10 Wikipedia 2015 Didecyldimethylammonium chloride (DDAC) [cited 2016 Jan 05]. Available from: http://en.wikipedia.org/wiki/Didecyldimethylammonium_chloride/
11 Dejobert Y Martin P Piette F Thomas P Bergoend H 1997 Contact dermatitis from didecyldimethylammonium chloride and bis-(aminopropyl)-lauryl amine in a detergent-disinfectant used in hospital Contact Derm 37 95 96 10.1111/j.1600-0536.1997.tb00050.x 9285176
12 Geier J Lessmann H Krautheim A Fuchs T 2013 Air borne allergic contact dermatitis caused by didecyldimethylammonium chloride in a geriatric nurse Contact Derm 68 123 125 10.1111/cod.12013 23289885
13 Organization for Economic Cooperation and Development 2009 OECD guidelines for the testing of chemicals. Test guideline 413 Subchronic inhalation toxicity: 90-day study OECD Paris
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