Subchronic exposure to nitrocellulose thinner vapour induces persistent testicular dysfunction and reversible prostatic stress in male Wistar rats

Abstract

Nitrocellulose thinner (NCT) is a widely used industrial solvent, yet the extent of its reproductive toxicity and the potential for recovery following cessation of exposure remain poorly understood. This study aimed to evaluate the subchronic effects of NCT vapor inhalation on the hypothalamic–pituitary–gonadal (HPG) axis, sperm quality, and prostatic integrity, as well as to determine the capacity for functional and structural recovery after a withdrawal period. Male Wistar rats were exposed to NCT vapor for 90 days, followed by a 90-day recovery (withdrawal) period. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, acid phosphatase (ACP), and prostate-specific antigen (PSA) were quantified. Sperm quality indices (count, motility, viability) and morphological defects were assessed, alongside histopathological examination of the prostate and testes. Subchronic NCTV exposure induced primary testicular dysfunction, characterized by significantly (p < 0.05) elevated FSH (0.74 ± 0.05 IU/L) and LH (0.55 ± 0.05 IU/L) alongside reduced testosterone (2.80 ± 0.47 ng/mL). Prostatic stress was evidenced by increased ACP and PSA levels and epithelial hyperplasia. Sperm quality was severely impaired, with a significant rise in total defects (15.50 ± 2.47%). Following withdrawal, prostatic markers and glandular architecture normalized, demonstrating significant regenerative potential. However, the HPG axis transitioned to secondary hypogonadotropic hypogonadism, with FSH, LH, and testosterone (0.71 ± 0.09 ng/mL) failing to recover. Furthermore, sperm parameters remained significantly lower than control levels, suggesting persistent damage to the germinal epithelium and spermatogonial stem cells. NCTV induces widespread reproductive toxicity. While prostatic damage is reversible upon withdrawal, testicular and endocrine impairments are persistent, likely due to oxidative injury and neuroendocrine toxicity. These findings highlight the significant long-term reproductive risks associated with industrial solvent exposure.