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Description of key information

Acute inhalation toxicity studies have been conducted on C4 F-isonitrile.  The acute oral toxicity of C4 F-isonitrile was waived.  The results of the studies are: 
Acute inhalation toxicity is greater than 10,000 ppm when tested according to a custom protocol.
Acute inhalation toxicity is less than 15,000 ppm when tested according to a custom protocol.

Key value for chemical safety assessment

Additional information

The acute inhalation toxicity of the test article was evaluated in male Sprague Dawley rats. This study was conducted according custom protocol and was not intended to be compliant with GLP guidelines. The test article was administered as received (as a gas). Rats (5/group) were exposed, whole body to the test article at 0, 5000, or 10000 ppm for a single 4-hour exposure. Control rats receiving 0 ppm of the test material were place in a separate chamber and treated in the same manner as the test groups with the exclusion of the addition of the test material. Of each group, 3 animals were euthanized on Day 1 post-dose for organ examination. The remaining 2 animals from each group were observed until Day 14 post-dose. Clinical observations (throughout study) and body weights (prior to exposure, Day 1, Days 2-4, Days 7-11, and Day 14) were recorded. At euthanasia, blood was collected. Following euthanasia, necropsy was performed on all animals, and lungs, liver, and kidneys were collected and weighed. Histopathological evaluation of the lungs and kidneys were also performed. Clinical observation at the 10,000 ppm exposure level included agitated appearance, sporadic respiratory rates, gasping, and a lack of response to noise stimuli. At the end of exposure, all animals were ataxic, had cool appendages, slow respiratory rates and three (3/5) animals had no grip strength. Clinical observations at the 5,000 ppm exposure level included slow, shallow, and sporadic respiratory patterns, gasping, lack of activity, and decreased response to noise stimuli. A decrease in body weight occurred on Days 1-4 in the 10,000 ppm animals and on Days 1-3 in the 5,000 ppm animals. Weights increased on Days 7 and 4 for the 10,000 and 5,000 ppm treated animals respectively. No gross lesions or other abnormalities were noted in any animal at gross necropsy. Average kidney, liver, and lung organ weights were similar between treated and control animals. No histopathological changes associated with the test article were observed (see additional histopathology report). Based on the results of the study, the 4-hour LC50 (gas) of the test article was > 10,000 ppm.


The acute inhalation toxicity of the test article was evaluated in male Sprague Dawley rats following a 4-hour exposure. This study was not GLP compliant. The study design was based on custom protocol. Five male rats received a 4-hour, whole body exposure to an atmosphere containing 15000 ppm test article. A control group of 5 males was similarly exposed to an atmosphere containing no test material. The animals were observed continuously during exposure and then once daily thereafter. Body weights were recorded at pretest and on Day 1. Gross necropsy was performed on all animals on Day 1. All test group animals were euthanized in extremis on Day 1. During exposure to the test article, the following clinical observations were noted: periodic gasping, slow and sporadic respiratory rates, periodic head shaking, lack of response to noise stimuli, and clear fluid on the lids of closed eyes. Prior to death on Day 1, all test group animals exhibited weight loss, shallow respiration, ataxic movement only when touched, severe depression, and normal color. Necropsy revealed slightly red lungs in all test group animals and pale-colored kidneys in 2 test group males when compared to control group animals. Based on the results of this study, the 4-hour inhalation LC50 for the test article is less than 15000 ppm.

Justification for classification or non-classification

The results for the test article meet the CLP classification criteria for Acute Toxicity Category 4 based on a 4-hour inhalation LC50 between 2500 and 20000 ppm.