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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Genetic toxicity: in vitro

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Administrative data

in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Toxicology and Carcinogenesis Studies of Pentaerythritol Tetranitrate (CAS No 78-11-5) with 80% D-Lactose Monohydrate (PETN, NF) in F344/N Rats and B6C3F1 MICE
John R. Bucher
Bibliographic source:
National Toxicology Program P.O Box 12233 Research Triangle Parc, NC 27709
Reference Type:
review article or handbook
Himiya otravlyayushtih veshtestv (Chemistry of poisonous substances)
Nekrasov V. V.
Bibliographic source:
Nauchnoe chimico-technicheskoe izdatelstvo

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
[3-nitrooxy-2,2-bis(nitrooxymethyl)propyl] nitrate
Cas Number:
Molecular formula:
[3-nitrooxy-2,2-bis(nitrooxymethyl)propyl] nitrate
Specific details on test material used for the study:
The presence in the molecule of a substance of the nitrogen atom associated with double bond oxygen almost always determines the toxicity of the compound. The reason most likely is that substances of this nature are easily recovering, i.e. they release oxygen and are strong oxidants. Therefore, all such compounds, such as nitro compounds R-NO2, nitroso compounds R-NO, nitric acid esters - nitrites RO-NO and nitric acid esters - nitrates RO-NO2, - substantially affect the organism in an analogous way destroy hemoglobin in the blood by oxidizing it to methaemoglobin. In addition, their poisonous effect is manifested in all the cells and tissues of the body.
Pentaerythritol Tetranitrate is the lipid soluble polyol ester of nitric acid belonging to the family of nitrovasodilators that exhibit vasodilatory property. Pentaerythritol tetranitrate releases free nitric oxide (NO) after denitration reaction, which triggers NO-dependent signaling transduction involving soluble guanylate cyclase (sGC). NO binds reversibly to the ferrous-heme center of sGC, thereby causes conformational change and activates the enzyme. Activation results in increasing cellular levels of cyclic guanosine monophosphate (cGMP) within vascular smooth muscle, which results in vasodilation mediated by cGMP-dependent protein kinases. Furthermore, this agent causes arterial and venous bed dilation in a dose-dependent manner.
Considering the fact that both PETN and Isopropyl nitrate are esters with nitric acid, we assume that the available data on genetic toxicity of PETN is valid also for Isopropyl nitrate.


Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced
Test concentrations with justification for top dose:
doses up to 10 mg/plate
Vehicle / solvent:
No data available.
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535
TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: all cell types tested

Applicant's summary and conclusion

The substance is not mutagenic in S.typhimirium strains TA98, TA100, TA 1535 or TAT1537.
There is no evidence of cancerogenic activity of the substance referred to.