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. 2019 Sep-Oct;33(5):1507-1519.
doi: 10.21873/invivo.11631.

Acute and 28-Day Repeated Inhalation Toxicity Study of Glycolic Acid in Male Sprague-Dawley Rats

Seong Kwang Lim  1 , Jean Yoo  1 , Haewon Kim  1 , Woong Kim  1 , Ilseob Shim  1 , Byung-Il Yoon  2 , Pilje Kim  1 , Seung DO Yu  1 , Ig-Chun Eom  3
Affiliations

Acute and 28-Day Repeated Inhalation Toxicity Study of Glycolic Acid in Male Sprague-Dawley Rats

Seong Kwang Lim et al. In Vivo. 2019 Sep-Oct.

Abstract

Background/aim: The use of glycolic acid is present in a variety of consumer products, including medicines, cleaners, cosmetics, and paint strippers. It has recently led to concerns about toxicity from inhalation exposure. Herein, the pulmonary toxicity of glycolic acid was investigated in rats.

Materials and methods: We conducted acute (~458 mg/m3) and sub-acute (~49.5 mg/m3) inhalation tests to identify the potential toxicities of glycolic acid.

Results: Inhalation exposure to glycolic acid in the acute and subacute inhalation tests did not cause any specific changes in clinical examinations, including body weight, organ weight, hematology, serum biochemistry, and histopathology. The polymorphonuclear neutrophils (PMNs) and inflammatory cytokines in Bronchoalveolar lavage fluid (BALF) increased in rats exposed to single and repeated inhalations. In the sub-acute test, the changes induced by glycolic acid were minor or returned to normal during the recovery period.

Conclusion: The No Observed Adverse Effect Concentration (NOAEC) for the nasal and pulmonary toxicity of glycolic acid was determined to be over 50 mg/m3 at the end of a 28-day inhalation test in male rats.

Keywords: Acute; glycolic acid; inhalation exposure; subacute; toxicity.

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Conflict of interest statement

There are no conflicts of interest to declare.

Figures

Figure 1
Figure 1. The pulmonary toxicities induced by the acute inhalation test of glycolic acid in rats. (A) Lactate dehydrogenase (LDH) activity, (B) Total protein level, (C) Polymorphonuclear leukocyte (PMN) count in bronchoalveolar lavage fluid (BALF). The values are expressed as a mean±SE of pentaplicate samples.
Figure 2
Figure 2. Change in pulmonary inflammation cytokines induced by glycolic acid in the acute inhalation test. (A) Interleukin-1beta (IL-1β), (B) Interleukin-6 (IL-6), (C) Monocyte chemoattractant protein-1 (MCP-1), (D) Macrophage inflammatory protein-2 (MIP-2), (E) Tumor necrosis factoralpha (TNF-α) in BALF. The values are expressed as a mean±SE of pentaplicate samples.
Figure 3
Figure 3. Histological features of the respiratory epithelial area of the nasal cavity in each group of rats in the acute inhalation study. No treatmentrelated abnormal findings were noted in the rats exposed to: i) 20 mg/m3 (low), ii) 100 mg/m3 (medium), and iii) 500 mg/m3 (high) of glycolic acid after inhalation for 4 hours. H&E. Scale bars=25 μm.
Figure 4
Figure 4. Histological features of the olfactory epithelial areas of the nasal cavity in each group of rats in the acute inhalation study. No treatmentrelated abnormal findings were noted in the rats exposed to: i) 20 mg/m3 (low), ii) 100 mg/m3 (medium), and iii) 500 mg/m3 (high) concentrations of glycolic acid after inhalation for 4 hours. Note an intraepithelial microcyst (arrow). H&E staining. Scale bars=25 μm.
Figure 5
Figure 5. Histological features of representative lungs of each group of rats in the acute inhalation study. No treatment-related abnormal findings were noted in the lungs of the rats exposed to: i) 20 mg/m3 (low), ii) 100 mg/m3 (medium), and iii) 500 mg/m3 (high) of glycolic acid by inhalation for 4 hours. b, bronchiole; tb, terminal bronchiole; a, alveoli. H&E staining. Scale bars=50 μm.
Figure 6
Figure 6. The pulmonary toxicities induced by subacute inhalation test of the glycolic acid in rats. (A) Lactate dehydrogenase (LDH) activity, (B) Total protein level, (C) Polymorphonuclear leukocyte (PMN) count in BALF. The values are expressed as a mean±SE of pentaplicate samples.
Figure 7
Figure 7. Changes in pulmonary inflammatory cytokines induced by glycolic acid in the subacute inhalation test. (A) Interleukin-1beta (IL-1β), (B) Interleukin-6 (IL-6), (C) Monocyte chemoattractant protein-1 (MCP-1), (D) Macrophage inflammatory protein-2 (MIP-2), (E) Tumor necrosis factoralpha (TNF-α) in BALF. The values are expressed as a mean±SE of pentaplicate samples.
Figure 8
Figure 8. Histological features of the respiratory epithelial area of the nasal cavity in each group of rats in the 28-day inhalation study. No treatmentrelated abnormal findings were noted in the rats exposed to: i) 2 mg/m3 (low), ii) 10 mg/m3 (medium), and iii) 50 mg/m3 (high) of glycolic acid for 6 hours/day, 5 days/week for 28 days. H&E staining. Scale bars=25 μm.
Figure 9
Figure 9. Histological features of the olfactory epithelial area of the nasal cavity in each group of rats in the 28-day inhalation study. No treatmentrelated abnormal findings were noted in the rats exposed to: i) 2 mg/m3 (low), ii) 10 mg/m3 (medium), and iii) 50 mg/m3 (high) of glycolic acid for 6 hours/day, 5 days/week, for 28 days. H&E staining. Scale bars=25 μm.
Figure 10
Figure 10. Histological features of representative lungs of each group of rats in the 28-day inhalation study. No treatment-related abnormal findings were noted in the lungs of the rats exposed to: i) 2 mg/m3 (low), ii) 10 mg/m3 (medium), and iii) 50 mg/m3 (high) of glycolic acid for 6 hours/day, 5 days/week for 28 days. b, bronchiole; tb, terminal bronchiole; a, alveoli. H&E staining. Scale bars=50 μm.
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