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Control, National Institute of Health, Korea Centers for Disease Control and Prevention, Seoul, Korea 2 Department of Otorhinolaryngology, College of Medicine, Seoul National University, Seoul, Korea

1 Lab. Anim. Res. 2010: 26(2), Prevalence of Laboratory Animal Allergy in Laboratory Workers Tae Jong Son 1, Jung Hwan Bae 1, Chae Seo Rhee 2 and Won Keun Seong 1, * 1 Division of Biosafety Evaluation and Control, National Institute of Health, Korea Centers for Disease Control and Prevention, Seoul, Korea 2 Department of Otorhinolaryngology, College of Medicine, Seoul National University, Seoul, Korea This study was designed to analyze the prevalence rates of laboratory animal allergy (LAA) in laboratory workers who perform researches with animals, and detect the mouse urinary allergen (Mus m 1) level in animal facilities for the purpose of establishing program for prevention of exposure to allergen. Study subjects were 240 employees who were working for two animal research institutions in Korea. Then the questionnaire and skin prick tests (SPTs) using twenty allergens were conducted with them. Presence of Mus m 1 in each air borne sample collected from animal facility was determined by using enzyme-linked immunosorbent assay. Through 240 questionnaire sheets, we found that; (1) 17.0% of workers in the direct exposure group answered that they had allergic symptoms due to laboratory animals; and (2) 6.2% of them had asthmatic symptoms. Twenty one subjects (27.6%) among the subjects with common allergens positive result and five subjects (6.6%) among the subjects with negative result showed a positive response to LAA under the SPTs. The Mus m 1 concentration (1.9 ng/m ) in the sample collected during cage exchange in mouse breeding room was up to 2.8 times higher than its concentration (0.48 ng/m ) in the sample collected at the stationary state. We suggest that LAA management programs including control of exposure to laboratory animal allergens should be considered as a measure to reduce the incidence of LAA and relieve the laboratory worker s allergic sensitivity to laboratory animals. Key words: Laboratory animal allergy, mus m 1, aero-allergen, exposure assessment Received 1 March 2010; Revised version received 17 May 2010; Accepted 10 June 2010 x»(laboratory Animal Allergy) x wš w xá w z ƒw w. x w» 11~44% 4~ 22% ƒ š (Robert and Gregg, 200). x ƒ 125,000 š (Seward, 1999; 2001), x w y l» š (Gordon et al., 2001). x» w šƒ t z,, sww ƒ x *Corresponding author: Won Keun Seong, Division of Biosafety Evaluation and Control, National Institute of Health, Korea Centers for Disease Control and Prevention, 194 Tongil-lo, Eunpyung-gu, Seoul , Korea Tel: Fax: wksung@nih.go.kr» w ww, x» w ƒ w (Cockcroft et al., 1981; Aoyama et al., 1992; Patel et al., 2000). p 17 w ü 5,641 ww ³» xy mw 2.1% ƒ x w» y w (Aoyama et al., 1992). ü» ü 16 x w ³ x w 1.% ƒ y» ƒ šw (Moon et al., 200). w xá š. x» Jackson 2,700 m y wš, ü 60 m xá» œ š. x ü w x x wš x ƒ 165

2 166 Tae Jong Son et al. wš. x w xá ƒ w x ƒ, x w» z w ƒ š. ù»,, w ƒ ü w, x w Á v ƒ. ü x ü w x xá w x» v w» y w» w xá» ü x w» xy wš x y ü x sƒw. y w ( x», x», q, i,, 1, 2, t, l, ) 10 x w (,,,» v, š, w l,,,, mö), k ( ), š ( ) w v w 107 w œ» w ww. v q 2cm 20 w n wš 15 ù z» w w q s³ k w (w s³ / k s³ ) 0.5 q w. w s³ / k s³ w 1+, 1 2+, 1 jš 2 +, 2 4+ w 2+ q w (Jang et al., 2009). ¼ t t ü x Á 240 w š,» ü x w 177, x w 6 w. 240 y w v š w 107 ( : 76, : 1 ).» ü Á s³ ù 1.5, 60.8%, x s³.8 (Table 1). w z ( q-2865y; z w m ). lò lm x w» v w.,», x w.» w y x w» xy, x» w w. t t ü x Á 240 w. v Allergie ergo (Allergopharma, Germany) ü 10 Ò l j œ» x w v Korpi (2004) xw ww. Gelatin filter TM ( µm pore size, 80 mm diameter, Sartorius-stedim Biotech, Germany)ƒ œ» e AirPortMD8 TM (Sartorius-stedim Biotech, Germany) w t t sƒ x ü,, k š ƒ 480 L œ» s w. k(stationary status) f w f w k(working status) œ» s w z p vl 20 o C w. ñ œ» x s w p vl % tween-20 sw 20 ml phosphate buffered saline (ph7.4) š 10 kw. vl,000 rpm 20 w sw d w. sw jp Vivaspin TM (Sartorius-stedim Biotech., Germany) w w, 00 µl w 4 o C w. ñn x ü d (MUP; Mouse urinary allergen, Mus m 1) k jp Mus m 1 ELISA kit TM (Indoor Biotechnologies, UK) w ww. Poly-clonal rabbit anti-mus

3 m 1 capture antibody biotinylated rabbit anti-mus m 1 antibody w Hollander (1997) w x xw ww, z d» Tecan Sunrise TM (ReTiSoft, Canada) w 492 nm Ÿ O.D (Optical Density) d w. Mus m 1 t v(0.16~2.5 ng/ml) w Intra-assay x z w š, w inter-assay x 10z ww. Mus m 1 sƒ w»w» w z w w (LOD; Limit of detection) w. w 2-fold ƒ û t w s³ (Mean absorbance of blanks)+2 t r (Standard deviation) w (Korpi et al., 2004). Mus m 1 t 2 w v z w Ÿ 492 nm q d Mus m 1 17 pg/ml š, w 0.05 ng/ m. Mus m 1 w intraassay s³.9%, inter-assay 1.4%. w, v Mus m 1 d m w SPSS TM version 18.0k (SPSS Inc, USA) w. 95% OR (Odds ratio) wš, P<0.05 m w š q w. Occupational allergy to laboratory animals 167 lò lm Á w» ü 240 w w 48.% ƒ y» xw, x w 4.5%, x w 42.9%ƒ y» w. x w w» x 17.0%ƒ ü». l ƒƒ 6.2% 4.8%. w» xy 17.0%(25/147) š, 1» 1.8%(5 /5 ), 15.4%(5 ~10 /5 ), 7.5%(10 /5 ) x w» (Table 1) ww v y w w» ƒ x w» 27.6%(21 /76 ) š, y w» x w w» 6.6%(5 /76 ) m w w (P<0.01) (Figure 1). Table 1. Comparison and sensitization rate of workers with and without laboratory animals by questionnaire Questionnaire (n=240) Direct (n=177) Indirect (n=6) OR a 95% CI b Demographics Gender Male (n) Female (n) Average age 0 Years of working with animals.8 - Sensitization Environment allergen 77 (4.5%) 27 (42.9%) Animal allergen 0 (17.0%) - Asthma 11 (6.2%) (4.8%) Expose to mice, h <5 hours 15/109 (1.8%) to 10 hours 2/1 (15.4%) hours /8 (7.5%) a Odds Ratio, b Confidence interval.

4 168 Tae Jong Son et al. Figure 1. The positive rate of laboratory animal allergy in positive population to common allergen was 27.6% (21/76) and that of negative population to common allergen was 6.6% (5/ 76), respectively, showed with statistical significance (P<0.01). Ò l ñ x ü Mus m L œ» s w w (0.05 ng/m ) d w. ü y k œ» Mus m ng/m w, s³ 0.48 ng/m. f k ü œ» Mus m ~.285 ng/m š, s³ 1.9 ng/m d y œ» Mus m 1 ƒ 2.8 ƒw (P<0.05) (Table 2). y ü w w d, k ü Mus m ng/m w. x ü f œ» Mus m ~5.810 ng/m š s³.09 ng/m d (Table 2). x w w xá š,» ü x w» 11~44% š š (Harrison, 2001; Wolfle and Bush, 2001; Robert and Gregg, 200). ü x w ƒ ƒw x ƒ š x w» ƒ g w» š. wš w» ü x w x w» xy w.» ü 240 y w w» ƒ x w (4.5%) w (42.9%) ƒ, x w x w w» 17.0%» ü x w» w w xy (Table 1). x 4~22% š (Robert and Gregg, 200), ü 6.2% ü 4.8% ƒ l, ü ƒ x» w w wz ƒ v w. q» ü x w, x w š» 107 y w 10 x w 10 w v ww. v» w» (8%) ƒ, w w» ƒƒ 8.9, 6.5% w» Table 2. Mus m 1 aero-allergen concentration during different tasks of laboratory animal care taking Mus m 1 concentration (ng/m ) Area Status No. of samples a Mean Range Office room 10 ND b ND Anteroom ±0.001 ND Mouse breeding room Stationary c ±0.161* ND-1.18 Cleaning room 10 ND ND Mouse breeding room 101.9±0.26* Cleaning room Working d 10.09± a The collected sample was 480 L, b No detection, c No working with laboratory animals, d Working with laboratory animals, *P<0.05 compared to stationary/working status.

5 (data not-shown). ƒ x y w» w ƒ y w. ù ƒ x w x w w v x» (6.0%) (.0%) m w w, (1.0%) w ƒ(p<0.05) šw (Jang et al., 2009).» ü x w x w x w» wš.» ü x w x w» w» ü x w x w ƒ wš. x w w» x w w x x x w» ü x w»z». w x ü k ü œ» Mus m 1 ƒ ng/m w š (Table 2), x w w x k mw x w w e w. x» w» ü x w» y w w w sƒ. w» 17%,, w» 11~26% w š (Bland et al., 1986; Venables et al., 1988; Aoyama et al., 1992; Cullinan et al., 1994; Hollander et al., 1996).» 1 5 w (1.8%; 15 /109 ), 5 10 (15.4%; 2 /1 ), 10 (7.5%; /8 ) x ¼» ƒw, w m w w (Table 1). ù Elliott (2007) x w x» ƒw š w, x ƒ» w w. x Occupational allergy to laboratory animals 169 w» y w r x w ƒ v w. total IgE» k ùkü t š x w w» total IgE ƒ ƒ (Renstrom et al., 1994; Hollander et al., 1996). total IgE eƒ, w w v ƒ š (Krakowiak et al., 2007). q total IgE d 5, w» w wš. w x w total IgE 150 KIU/L v mw x w w» ƒ 75% q (Jang et al., 2009). w y w w» ƒ w w» y w w» 4 y w, m w (P<0.01) (Figure 1). q total IgE e y w» x x» dw ƒ. x œ» x sƒw» w ü 480 L œ» s w Mus m 1 d w (LOD; 0.05 ng/m ). 1 15z y w 1z y 0.5~0.8 L œ» w 1 450~720 L œ» y w», s 480 L x ü œ» ƒ 1 x ü y w œ» d. ü Mus m 1 y e k f 2.8 ƒ (Table 2). f œ» Mus m ~5.810 ng/m, 70% wš ü y Mus m 1 ƒ w w d (Table 2). x ü œ» x y w ƒ e k x ü œ» 10 Gordon (1994) šw. w Jones (1995) x ü ƒ 15% 65%¾ ƒ œ»

6 170 Tae Jong Son et al. ƒ 6 šw» x y w ƒ w. x» w, (MUP; Mouse urinary protein) ƒ ng/m ü x» w w ƒ 5ng/m ƒw š š (Gordon et al., 2001). x x ƒ x w k ü œ» Mus m 1 ƒ 0.5 ng/m ƒ w dw. ù x w ù x w s» ng/m Mus m 1 ƒ š. x x w s» ƒ» ƒ w x l w. x w» ü x w» xy x ü Mus m 1 œ» d w œ» y w. w x ü x x w» ƒ w e ƒ w. q p» ü x w x w w x» w š y w (Jang et al., 2009),» ü x w ƒ š.» ü x w» y w d x x x w š w x» ƒ ƒ v w. ü w x ü x ƒ x x w» ƒ g z ƒw.» ü x w w x» y ƒ v w. q ƒ ü w w. k Aoyama, K., Ueda, A., Manda, F., Matsushita, T., Ueda, T. and Yamauchi, C. (1992) Allergy to laboratory animals: an epidemiological study. Br. J. Ind. Med. 49, Bland, S.M., Levine, M.S., Wilson, P.D., Fox, N.L. and Rivera, J.C. (1986) Occupational allergy to laboratory animals: An epidemiologic survey. J. Occup. Med. 28, Cockcroft, A., Edwards, J., McCarthy, P. and Andersson, N. (1981) Allergy in laboratory animal workers. Lancet 1, Cullinan, P., Lowson, D., Nieuwenhuijsen, M.J., Gordon, S., Tee, R.D. and Venables, K.M. (1994) Work related symptoms, sensitization and estimated exposure in workers not previously exposed to laboratory rats. Occup. and Environ. Med. 51, Elliott, L., Heederik, D., Marshall, S., Peden, D. and Loomis, D. (2007) Incidence of allergy and allergy symptoms among workers exposed to laboratory animals. Occup. and Environ. Med. 62, Gordon, S., Fisher, S.W. and Raymond, R.H. (2001) Elimination of mouse allergens in the working environment: Assessment of individually ventilated cage systems and ventilated cabinets in the containment of mouse allergens. J. Allergy Clin. immumol. 108(2), Gordon, S., Tee, R.D., Nieuwenhuijsen, M.J., Lowson, D., Harris, J. and Newman Taylor, A.J. (1994) Measurement of airborne rat urinary allergen in an epidemiological study. Clin. Exp. Allergy 24, Harrison, D.J. (2001) Controlling exposure to laboratory animal allergens. ILAR J. 42(1), Hollander, A., Doekes, G. and Heederik, D. (1996) Cat and dog allergy and total IgE as risk factors of laboratory animal allergy. J. Allergy Clin. Immunol. 98, Hollander, A., Van Run, P., Spithoven, J., Heederik, D. and Doekes, G. (1997) Exposure of laboratory animal workers to airborne rat and mouse urinary allergens. Clin. Exp. Allergy 27, Jang, J.H., Kim, D.W., Kim, S.W., Kim, D.Y., Seong, W.K., Son, T.J. and Rhee, C.S. (2009) Allergic rhinitis in laboratory animal workers and its risk factors. Ann. Allergy Asthma Immunol. 102, Jones, R., Kacergis, J., MacDonald, M., McKnight, F., Turner, W., Ohman, J. and Paigen, B. (1995) The effect of relative humidity on mouse allergen levels in an environmentally controlled mouse room. J. Am. Ind. Hyg. Assoc. 56, Korpi, A., Mantyjarvi, R., Rautiainen, J., Kaliste, E., Kalliokoski, P. and Renström, A. (2004) Detection of mouse and rat urinary aeroallergens with an improved ELISA. J. Allergy Clin. Immunol. 11, Krakowiak, A., Wiszniewska, M., Krawczyk, P., Szulc, B., Wittczak, T., Walusiak, J. and Palczynski, C. (2007) Risk factors associated with airway allergic diseases from exposure to laboratory animal allergens among veterinarians. Int. Arch. Occup. Environ. Health 80, Moon, J.Y., Kim, C.W., Cho, J.H., Chang, J.H., Choi, S.Y., Kwon, N.Y. and Hong, C.S. (200) Laboratory animal allergy in laboratory animal workers. J. Kor. Asthma Allergy Clin. Immunol. 2,

7 Occupational allergy to laboratory animals 171 Patel, N.J., Olson, P., Lumby, D., Fine, J.P. and Bush, R.K. (2000) Laboratory animal allergy. (Abastract) J. Allergy Clin. Immunol. 105, S72. Renstrom, A., Malmberg, P., Larsson, K., Sundblad, B.M. and Larsson, P.H. (1994) Prospective study of laboratory-animal allergy: factors predisposing to sensitization and development of allergic symptoms. Allergy 49, Robert, K.B. and Gregg, M.S. (200) Laboratory animal allergies: An Update. ILAR J. 44(1), Seward, J.P. (1999) Occupational allergy to animals. J. Occup. Med. 14, Seward, J.P. (2001) Medical surveillance of allergy in laboratory animal handler. ILAR J. 42, Venables, K.M., Upton, J.L., Hawkins, E.R., Tee, R.D., Longbottom, J.L. and Newman Taylor, A.J. (1988) Smoking, atopy, and laboratory animal allergy. Br. J. Indust. Med. 45, Wolfle, T.L. and Bush, R.K. (2001) The science and pervasiveness of laboratory animal allergy. ILAR J. 42(1),

605.fm

605.fm Journal of the Korean Housing Association Vol. 19, No. 6, 2008 y k y p w sƒ Care-giver s Needs and Evaluation on the Actual Condition of the Playgrounds in Child Care Facilities y* Choi, Mock-Wha x **