Revisiting the testicular toxicity of cyanide: Assessment of the new and existing literature

Abstract

Background: Based on new testing, we re-assess U.S. EPA and California OEHHA conclusions regarding male reproductive toxicity associated with cyanide exposure. Methods: Literature identified by ATSDR, ECETOC and EPA was complemented by studies conducted after 2006. Relevant studies were scored for quality using ToxRTool. Results: Eleven pertinent animal investigations were identified; five with quality scores of 1 were evaluated in-depth. The NTP 13-week drinking water study of NaCN in rats reported significantly decreased water intakes and reduced cauda epididymal weights; altered sperm parameters occurred in high-dose rats. When compared to contemporaneous historical control data (HCD), the mean cauda epididymal weights of cyanide-treated rats in the NTP study were within HCD, whereas control weights exceeded HCD. A new 13-week drinking water study used the same design with additional features (individually caged rats, “paired water” controls, thyroid hormone determinations, post-treatment recovery) and found a smaller decrease in water consumption (11% versus 18% at 300 ppm) and no treatment-related changes in male reproductive measures. Although thyroid/parathyroid weights were increased at 300 ppm, histopathology and thyroid hormone levels were unaffected. The remaining high-quality cyanide studies reported no adverse findings in male reproductive organs. Unconfounded sperm measures were not adversely affected in any quality 1 studies. Conclusions: Changes in the male reproductive system reported after cyanide exposure in the NTP study were not reproducible, unlikely to be treatment-related, and should not be used as the sole basis for human health assessments.