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. 2022 Apr 15:359:22-30.
doi: 10.1016/j.toxlet.2022.01.011. Epub 2022 Jan 29.

Toxicity of high-molecular-weight polyethylene glycols in Sprague Dawley rats

Jia-Long Fang  1 , Michelle M Vanlandingham  2 , Frederick A Beland  2 , Robert P Felton  3 , Mackean P Maisha  3 , Greg R Olson  4 , Ralph E Patton  4 , Amy S Rosenberg  5 , Gonçalo Gamboa da Costa  2
Affiliations

Toxicity of high-molecular-weight polyethylene glycols in Sprague Dawley rats

Jia-Long Fang et al. Toxicol Lett. .

Abstract

Polyethylene glycol (PEG) is present in a variety of products. Little is known regarding the accumulation of high-molecular-weight PEGs or the long-term effects resulting from PEG accumulation in certain tissues, especially the choroid plexus. We evaluated the toxicity of high-molecular-weight PEGs administered to Sprague Dawley rats. Groups of 12 rats per sex were administered subcutaneous injections of 20, 40, or 60 kDa PEG or intravenous injections of 60 kDa PEG at 100 mg PEG/kg body weight/injection once a week for 24 weeks. A significant decrease in triglycerides occurred in the 60 kDa PEG groups. PEG treatment led to a molecular-weight-related increase in PEG in plasma and a low level of PEG in cerebrospinal fluid. PEG was excreted in urine and feces, with a molecular-weight-related decrease in the urinary excretion. A higher prevalence of anti-PEG IgM was observed in PEG groups; anti-PEG IgG was not detected. PEG treatment produced a molecular-weight-related increase in vacuolation in the spleen, lymph nodes, lungs, and ovaries/testes, without an inflammatory response. Mast cell infiltration at the application site was noted in all PEG-treated groups. These data indicate that subcutaneous and intravenous exposure to high-molecular-weight PEGs produces anti-PEG IgM antibody responses and tissue vacuolation without inflammation.

Keywords: Anti-PEG antibody; Choroid plexus; Polyethylene glycol; Vacuolation.

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Conflict of interest statement

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1.
Figure 1.
(a) Detection of PEG in plasma, urine, and feces using SDS-PAGE with iodine staining assay. (b) The levels of PEG in plasma, urine, and feces. Each group consisted of 12 animals per sex, except for the female 60 kDa PEG subcutaneous injection group and the female saline intravenous injection group, each of which had 11 animals. Columns and bars are the mean and standard deviation. #Significant (p < 0.05) molecular-weight-related trend. ^Significant (p < 0.05) difference between subcutaneous and intravenous injection.
Figure 1.
Figure 1.
(a) Detection of PEG in plasma, urine, and feces using SDS-PAGE with iodine staining assay. (b) The levels of PEG in plasma, urine, and feces. Each group consisted of 12 animals per sex, except for the female 60 kDa PEG subcutaneous injection group and the female saline intravenous injection group, each of which had 11 animals. Columns and bars are the mean and standard deviation. #Significant (p < 0.05) molecular-weight-related trend. ^Significant (p < 0.05) difference between subcutaneous and intravenous injection.
Figure 2.
Figure 2.
(a) Detection of PEG in CSF using SDS-PAGE with iodine staining assay. (b) The prevalence and level of PEG in CSF. The prevalence is reported as the number of animals with detectable PEG per number of animals examined. The concentrations of PEG (μg/ml) are presented as the mean and standard deviation if the number of PEG-positive samples was ≥ 3. n.d.: not detected.
Figure 3.
Figure 3.
The choroid plexuses from a saline control rat and rats administered 20, 40, and 60 kDa PEGs subcutaneously at 100 mg PEG/kg once a week for 24 weeks. Each group consisted of 12 animals per sex and all animals were evaluated histopathologically. Arrows indicate vacuoles. All images are 40X objective and H&E stain.
Figure 4.
Figure 4.
The skin at the application site from a saline control rat and rats administered 20, 40, and 60 kDa PEGs subcutaneously at 100 mg PEG/kg once a week for 24 weeks. Each group consisted of 12 animals per sex and all animals were evaluated histopathologically. Arrows indicate vacuoles and arrow heads indicate mast cell infiltration. All images are 40X objective and H&E stain.
See this image and copyright information in PMC

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