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Description of key information

According to results in rats and mice in the 14 days and 14 weeks- repeated dose toxicity assays, the value of acute LD50 (oral) can be considered as higher than the threshold for classification in any oral acute toxicity hazard categories. No additional reliable studies on acute toxicity are available. Due to explosive properties of the substance, no further testing could be conducted.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
A reliable study on chronic oral toxicity is available (please see attached).
Interpretation of results:
GHS criteria not met
Executive summary:

The U.S. National Toxicology program (NTP) conducted in 1989, a series of toxicity assay in rats and mice on pentaerythritol tetranitrate (PETN). Due to its explosivity hazard, the testing material was stabilized with lactose in a 1:4 ratio. The following tests were carried out in F344 rats and B6C3F1 mice:

- Subacute: 14 days repeated dose toxicity

- Subchronic: 13-14 weeks

- Chronic: 2 years

All mice lived to the end of the study of fourteen days and fourteen weeks (Tables 15 and 16 in NTP, 1989 study). Also all rats lived to the end of the studies (Tables 7 and 8 in NTP, 1989 study).

Results of the fourteen days study showed no deads in mice at doses higher than this threshold; maximum doses were 2.587 and 3.333 mg/kg-bw/day in males and females respectively. As for rats the higher dose was 909 and 1087 mg/kg-bw/day in males and females not causing either any dead.

Similarly, no deads in rats occurred either in the 13-weeks study at higher doses as 625 and 931 mg/kg-bw/day in males and females nor in mice at 2163 and 3170 mg/kg-bw/day in males and females.

A well established rule of thumb in toxicology makes a relation between the doses to cause deads at acute, subacute and subchronic exposure; this is acute LD50 can be expected to be at least twice the subacute NOAEL and six time the subcronic NOAEL.

Therefore, according to results in rats and mice in the 14 days and 14 weeks- repeated dose toxicity assays, the value of acute LD50 can be considered as higher than the threshold for classification in any acute toxicity hazard categories.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

PETN physiological effects are similar to those of the other aliphatic nitrates (vasodilator). To a certain extent, it is possible to consider that the acute effects of exposure to PETN are similar to those of nitroglycerin. Hypotension and increased respiratory rate may both occur, but to a lesser degree than is observed with nitroglycerin. In contrast to nitroglycerin, little reflex tachycardia is observed with PETN. Dyspnea and convulsions have also been reported.

Justification for classification or non-classification