Table 3.

Key conclusions for TCE noncancer toxicity.

Tissue or organ system	Key conclusions as to human health hazard
Central nervous system	Strong evidence, based on multiple human and experimental animal studies, that TCE causes
	Changes in trigeminal nerve function or morphology
	Impairment of vestibular function.
	Limited evidence, primarily from experimental animal studies, with fewer/more limited human studies, that TCE causes
	Delayed motor function, including during neurodevelopment
	Changes in auditory, visual, and cognitive function or performance.
Kidney	Strong evidence, based on experimental animal studies, a few human studies, and mechanistic studies, that TCE causes nephrotoxicity, particularly in the form of tubular toxicity. Nephrotoxicity is likely mediated primarily through the TCE GSH conjugation metabolite DCVC.
Liver	Limited evidence in humans and strong evidence from experimental animal studies that TCE causes hepatotoxicity but not necrosis. Mice appear to be more sensitive than other experimental species, and hepatotoxicity is likely mediated through oxidative metabolites including, but not exclusively, TCA.
Immune system	Strong evidence, based on multiple human and experimental animal studies, that TCE exposure causes
	Autoimmune disease, including scleroderma
	A specific type of generalized hypersensitivity disorder.
	Limited evidence, primarily from experimental animal studies, with fewer/more limited human studies, that TCE causes immunosuppression.
Respiratory tract	Suggestive evidence, primarily from short-term experimental animal studies, that TCE causes respiratory tract toxicity, primarily in Clara cells.
Reproductive system	Strong evidence, based on multiple human and experimental animal studies, that TCE causes male reproductive toxicity, primarily through effects on the testes, epididymides, sperm, or hormone levels.
	Suggestive evidence, based on few/limited human and experimental animal studies, that TCE causes female reproductive toxicity.
Development	Strong evidence, based on weakly suggestive epidemiologic studies, limited experimental animal studies, and multiple mechanistic studies, that TCE causes fetal cardiac malformations; limited experimental evidence that oxidative metabolites, such as TCA and/or DCA, cause similar effects.
	Limited evidence, primarily from experimental animal studies, with weakly suggestive epidemiologic studies, that TCE causes fetal malformations (in addition to cardiac), prenatal losses, decreased growth or birth weight of offspring, and alterations in immune system function.
Abbreviations: DCVC, S-dichlorovinyl-l-cysteine. Data from U.S. EPA (2011d).