Registration Dossier

Administrative data

Description of key information

There are no data on the intermediate, however the specific component n-hexane is recognised as having neurotoxic activity. 
These effects are also briefly discussed in the section on repeated dose toxicity (5.6.3).

Key value for chemical safety assessment

Additional information

There are no data on the intermediate; however there are data on specific components present to indicate neurotoxic activity and trigger classification.


Lammers et al (2009) studied the neurobehavioral effects of cyclohexane. There was no compelling evidence for treatment related effects at 860 mg/m3 and the reports of headache, throat and eye irritation were 'self reported' and subjective. Evidence of only minimal effects in rats exposed to 28,000 mg/m3 suggests that effects in humans exposed to much lower levels would be unlikely. Based two studies (Lammers et al, 2009; Hissink et al, 2009), it was concluded that with the validated human PBPK model it was possible to calculate an exposure level which would lead to neurobehavioral effects in human. This dose would be 3,900 ppm (13,400 mg/m3) leading to a NOAEC of 1,200 ppm (4,125 mg/m3). 


In animals following oral or inhalation exposure n-hexane can produce neurologic dysfunction of motor or sensorimotor nerves resulting in weight loss and paralysis (Spencer and Schaumberg, 1985). Epidemiological studies on n-hexane have shown an association between inhalation exposure to n-hexane and neurological symptoms in occupationally exposed individuals. The NOAEC for peripheral neuropathy is reported to be 20 ppm (70 mg/m3) (UK HSE, 1990).


Toluene exposure can produce central nervous system pathology in animals after high oral doses. In humans neuropsychological effects have been reported, particularly when exposures are not well controlled. There was no evidence that long-term exposure to toluene at 26 ppm for 21 years had any effects on cognitive function (Seeber et al, 2004).




Additional References


UK HSE (1990). N-Hexane occupational exposure standard. UK HSE Review 1990, D34-D35, Published 1993



Justification for classification or non-classification

See section 5.6 for overall classification for repeated dose toxicity.