Pulmonary exposure to cellulose nanocrystals caused deleterious effects to reproductive system in male mice

Abstract

Over the past several years there has been an increased number of applications of cellulosic materials in many sectors, including the food industry, cosmetics, and pharmaceuticals. However, to date, there are few studies investigating the potential adverse effects of cellulose nanocrystals (CNC). The objective of this study was to determine long-term outcomes on the male reproductive system of mice upon repeated pharyngeal aspiration exposure to CNC. To achieve this, cauda epididymal sperm samples were analyzed for sperm concentration, motility, morphological abnormalities, and DNA damage. Testicular and epididymal oxidative damage was evaluated, as well as histopathology examination of testes. In addition, changes in levels of testosterone in testes and serum and of luteinizing hormone (LH) in serum were determined. Three months after the last administration, CNC exposure significantly altered sperm concentration, motility, cell morphology, and sperm DNA integrity. These parameters correlated with elevated proinflammatory cytokines levels and myeloperoxidase (MPO) activity in testes, as well as oxidative stress in both testes and epididymis. Exposure to CNC also produced damage to testicular structure, as evidenced by presence of interstitial edema, frequent dystrophic seminiferous tubules with arrested spermatogenesis and degenerating spermatocytes, and imbalance in levels of testosterone and LH. Taken together, these results demonstrate that pulmonary exposure to CNC induces sustained adverse effects in spermatocytes/spermatozoa, suggesting male reproductive toxicity.

The Crystallinity and Aspect Ratio of Cellulose Nanomaterials Determine Their Pro‐Inflammatory and Immune Adjuvant Effects In Vitro and In Vivo

“…While currently there are no published data revealing a safety concern for nanocellulose in the workplace or in consumer products, experimental evidence has been collected for the potential hazardous effects of CNCs and CNFs . While most cellular studies have addressed cytotoxicity, inflammation and genotoxicity, which can be related to differences in the cellular uptake of CNCs versus CNFs or their ability to generate oxidative stress, most in vivo studies have focused on the effects in the lung and the reproductive system . For instance, pulmonary exposure to CNCs is capable of generating dose‐dependent pro‐inflammatory effects and oxidative stress, while CNFs are capable of inducing TH1 polarizing effects in the lung .…”

A critical review of the current knowledge regarding the biological impact of nanocellulose

“…Further evidence was shown that these biochemical effects led to significant genotoxicity [94]. In a further study, a similar author team elucidated further that the genotoxic effects were highly detrimental to the male reproductive system [95]. …”

Cellulose Nanocrystals as a Sustainable Raw Material: Cytotoxicity and Applications on Healthcare Technology

“…However, to date, limited data are available describing adverse health outcomes elicited by CNCs. Therefore, the concept that CNCs are biocompatible and non‐hazardous, justified due to the fact that they are biobased, nanosized materials and can be extracted from natural sources, must be evaluated carefully and critically, since few studies have demonstrated that these materials might have toxic effects on cells …”