Registration Dossier

Administrative data

Description of key information

One sub-chronic oral study in Sprague-Dawley rats (28 day) which is a GLP guideline study.  
One sub-chronic inhalation study in Spraque-Dawley rats which is a GLP, OECD 422 study; a combined repeated inhalation exposure study wtih the reproduction/developmental screening test.
One chronic inhalation study in male and female Long Evans Rats. Study duration was up to 21.5 months at 100 ppm 1-nitropropane.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
30 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
91 mg/m³
Study duration:
subacute
Species:
rat

Mode of Action Analysis / Human Relevance Framework

Additional information

Oral: In a 28 -day (sub acute) oral gavage study in male and female Spraque-Dawley rats exposed to 0, 10, 30 and 100 mg/kg/day of 1 -nitropropane, no treatment related effects were seen at the 10 and 30 mg/kg/d dose levels (NOEL = 30 mg/kg/d). At the 100 mg/kg/day level (LOAEL), the treatment related effects were hunched posture, lethargy, and axatia. Death occurred in one high dose male. Also, observed in the high dose group was a slight decrease in body weight gain in males and an increased in brain weight.

In a repeat dose inhalation exposure study with reproductive/developmental screening (OECD 422) male and female Spraque-Dawley rats were exposed to 0, 25, 50, or 100 ppm of 1 -nitropropane for 6 hours/day, 7 days/week. The only treatment related effects were changes in the nasal tissue consisting of very slight or slight degeneration of the olfactory epithelium and chronic active inflammation of the squamous epithelium in the female at 50 ppm and males at 100 ppm. Therefore the NOEC was set at 50 ppm.

The chronic inhalation toxicity study in Long Evans rats at 100 ppm of 1 -nitropropane did not show any treatment related effects.

Justification for classification or non-classification

Based on a 28 day oral study treatment related effects were observed at the 100 mg/kg/day dose. Therefore 1 -nitropropane can be classified as a Catagory 2 substance according to GHS.

No target organ was identified in the 28 day oral rat study. Although, brain weights were increased at the end of the study, there was no histopathological correlate. And in the recovery group, there was no evidence of increased brain weight indicating the effects were transient. Furthermore, signs of ataxia, hunched posture and lethargy are commonly seen in moribund animals and the hunch posture seen in two females is a non-specific sign of stress. Neither observation is indicative of CNS being a target organ for 1 -nitropropane.