Assessment of respiratory and systemic toxicity of Benzalkonium chloride following a 14-day inhalation study in rats

Choi, Hye-Yeon; Lee, Yong-Hoon; Lim, Cheol-Hong; Kim, Yong-Soon; Lee, In-Seop; Jo, Ji-Min; Lee, Ha-Young; Cha, Hyo-Geun; Woo, Hee Jong; Seo, Dong-Seok

doi:10.1186/s12989-020-0339-8

Table 5 Histopathological assessment of the lung and nasal cavity tissues

From: Assessment of respiratory and systemic toxicity of Benzalkonium chloride following a 14-day inhalation study in rats

	Main group
Sex	Male				Female
Concentration (mg/m³)	0	0.8	4	20	0	0.8	4	20
Lung
Number of animals	5	5	5	5	5	5	5	5
Degeneration/regeneration, terminal bronchiolar epithelium	(0)	(0)	(2)	(5)	(0)	(0)	(0)	(3)
Minimal	0	0	2	3	0	0	0	3
Mild	0	0	0	2	0	0	0	0
Mean ± SD	0	0	0.40 ± 0.55	1.40 ± 0.55	0	0	0	0.60 ± 0.55
Hypertrophy/hyperplasia, mucous cells, bronchi/bronchiole	(0)	(5)	(5)	(3)	(0)	(3)	(5)	(4)
Minimal	0	0	0	2	0	3	1	3
Mild	0	5	3	1	0	0	2	1
Moderate	0	0	2	0	0	0	2	0
Mean ± SD	0	2.00 ± 0.00	2.40 ± 0.55	0.80 ± 0.84	0	0.60 ± 0.55	2.20 ± 0.84	1.00 ± 0.71
Smooth muscle hypertrophy, bronchioloalveolar junction	(0)	(0)	(3)	(5)	(0)	(0)	(0)	(3)
Minimal	0	0	3	5	0	0	0	3
Mean ± SD	0	0	0.60 ± 0.55	1.00 ± 0.00	0	0	0	0.60 ± 0.55
Infiltration, eosinophil, perivascular	(0)	(1)	(3)	(1)	(0)	(0)	(0)	(2)
Minimal	0	1	3	1	0	0	0	2
Mean ± SD	0	0.20 ± 0.45	0.60 ± 0.55	0.20 ± 0.45	0	0	0	0.40 ± 0.55
Cellular debris, alveolar lumen	(0)	(0)	(3)	(2)	(0)	(0)	(0)	(1)
Minimal	0	0	3	2	0	0	0	1
Mean ± SD	0	0	0.60 ± 0.55	0.40 ± 0.55	0	0	0	0.20 ± 0.45
Nasal cavity
Number of animals	5	5	5	5	5	5	5	5
Ulceration with suppurative inflammation, respiratory epithelium	(0)	(0)	(0)	(1)	(0)	(0)	(0)	(2)
Mild	0	0	0	1	0	0	0	1
Marked	0	0	0	0	0	0	0	1
Mean ± SD	0	0	0	0.40 ± 0.89	0	0	0	1.20 ± 1.79
Ulceration with suppurative inflammation, transitional epithelium	(0)	(0)	(0)	(3)	(0)	(0)	(0)	(0)
Mild	0	0	0	1	0	0	0	0
Moderate	0	0	0	0	0	0	0	1
Marked	0	0	0	2	0	0	0	0
Mean ± SD	0	0	0	2.00 ± 2.00	0	0	0	0.60 ± 1.34
Squamous metaplasia, respiratory epithelium	(0)	(0)	(0)	(5)	(0)	(0)	(0)	(5)
Minimal	0	0	0	0	0	0	0	1
Mild	0	0	0	2	0	0	0	2
Moderate	0	0	0	3	0	0	0	1
Marked	0	0	0	0	0	0	0	1
Mean ± SD	0	0	0	2.20 ± 1.10	0	0	0	2.40 ± 1.14
Squamous metaplasia, transitional epithelium	(0)	(0)	(0)	(5)	(0)	(0)	(0)	(1)
Minimal	0	0	0	0	0	0	0	4
Mild	0	0	0	4	0	0	0	1
Moderate	0	0	0	1	0	0	0	0
Mean ± SD	0	0	0	1.40 ± 0.89	0	0	0	1.20 ± 0.45
Erosion with necrosis, respiratory epithelium	(0)	(0)	(0)	(5)	(0)	(0)	(0)	(3)
Minimal	0	0	0	3	0	0	0	0
Mild	0	0	0	1	0	0	0	1
Moderate	0	0	0	1	0	0	0	1
Marked	0	0	0	0	0	0	0	1
Mean ± SD	0	0	0	1.60 ± 0.89	0	0	0	1.80 ± 1.79
Erosion with necrosis, transitional epithelium	(0)	(0)	(0)	(5)	(0)	(0)	(0)	(4)
Minimal	0	0	0	2	0	0	0	1
Mild	0	0	0	1	0	0	0	0
Moderate	0	0	0	1	0	0	0	1
Marked	0	0	0	1	0	0	0	2
Mean ± SD	0	0	0	2.20 ± 1.30	0	0	0	2.40 ± 1.82
Hypertrophy/hyperplasia, mucous cells, respiratory epithelium	(0)	(5)	(5)	(5)	(0)	(5)	(5)	(5)
Minimal	0	0	1	1	0	0	1	0
Mild	0	3	0	2	0	0	2	5
Moderate	0	2	4	2	0	4	2	0
Marked	0	0	0	0	0	1	0	0
Mean ± SD	0	2.40 ± 0.55	2.60 ± 0.89	2.20 ± 0.84	0	3.20 ± 0.45	2.20 ± 0.84	1.20 ± 0.45
Metaplasia, mucous cells, transitional epithelium	(0)	(5)	(5)	(0)	(0)	(5)	(5)	(0)
Minimal	0	0	4	0	0	0	1	0
Mild	0	1	1	0	0	1	4	0
Moderate	0	4	0	0	0	4	0	0
Mean ± SD	0	2.80 ± 0.45	1.20 ± 0.45	0	0	2.80 ± 0.45	1.80 ± 0.45	0
Atrophy, olfactory epithelium	(0)	(0)	(0)	(1)	(0)	(0)	(0)	(2)
Mild	0	0	0	1	0	0	0	1
Moderate	0	0	0	0	0	0	0	1
Mean ± SD	0	0	0	0.20 ± 0.45	0	0	0	0.60 ± 0.89

0: unremarkable = no presence of histopathologic lesion; 1: minimal = lesions involving< 10% of the tissue of each organ; 2: mild = lesions involving< 10–30% of the tissue of each organ; 3: moderate = lesions involving< 30–50% of the tissue of each organ; 4: marked = lesions involving< 50–70% of the tissue of each organ; 5: severe = lesions involving> 70% of the tissue of each organ

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