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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Administrative data

Link to relevant study record(s)

Description of key information

Data from studies conducted in mice and rats support rapid absorption, limited tissue distribution and extensive urinary excretion of piperonal following oral administration.  The major urinary metabolites are piperonylglycine and piperonylic acid.  Dermal absorption has not been demonstrated, and despite its small size and low lipophilicity, absorption of piperonal via the inhalation route would not be expected due to its very low vapour pressure and therefore minimal potential for exposure via this route.  Therefore based upon the available data, it is concluded that piperonal will not bioaccumulate.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Heliotropin is a small crystalline substance with low lipophilicity and low vapour pressure (molecular weight of 150.13 g/mol; LogKow = 1.2; vapour pressure = 2 Pa at 20°C) [1,2,3]. It has a melting point of

35-37°C, suggesting that it exists as a liquid at physiologically relevant temperatures [1]. Data from studies conducted in mice and rats support rapid absorption, limited tissue distribution, and extensive urinary excretion of heliotropin following oral administration [4,5]. When administered to mice, an oral gavage dose of radiolabelled heliotropin was rapidly metabolized and excreted, with only very limited amounts of radiocarbon identified at 48 hours post-dosing in the intestine and liver (0.4% of the administered dose in each organ) or the remaining carcass (1.2% of the administered dose).

In both mice and rats, the majority of a single oral dose of heliotropin was accounted for in the urine soon after dosing. In mice, nearly 90% of the dose was recovered in the urine within 12 hours of dosing, while 92.6% of the dose was recovered in the urine of rats within 24 hours of dosing. In both species, the major urinary metabolite was piperonylglycine. In rats, the species for which quantitative data are available, piperonylglycine accounted for 71% of the administered dose of heliotropin at 24 hours post-dosing while piperonylic acid accounted for 20% of the dose.

Dermal absorption of heliotropin is expected to be minimal, given its relatively low lipophilicity, the lack of any systemic toxicity observed in rats administered an acute dermal dose of 5,000 mg/kg body weight, and the general lack of dermal irritation that has been observed in reliable studies conducted in humans, rats, and guinea pigs.

Toxicokinetic and toxicological data were not identified for the inhalation route of exposure. Although its small size and low lipophilicity would suggest the potential for absorption, exposure and possible absorption of heliotropin via the inhalation route would not be expected to occur based solely on its very low vapour pressure (2 Pa).

Heliotropin was demonstrated to exert an inhibitory effect on cytochrome P450 (CYP450)-mediated oxidative reactions in rat nasal microsome preparations but not in microsome preparations from rat liver [6], suggesting minimal potential for alteration of the metabolism of other substances known to be metabolized by hepatic CYP450.

Based on the available data demonstrating the rapid oral absorption of heliotropin and its efficient metabolism and urinary excretion, and taking into consideration its low molecular weight and low lipophilicity, heliotropin is not expected to bioaccumulate.


[1] The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (14th Edition), 1996.

[2] Rudio J. 1997. Partition coefficient n-octanol/water of HELIOTROPINE according to OECD Guideline N. 117. Givaudan Roure SA, Ecotoxicological Laboratory 5, ch. de la Parfumerie CH-1214 Vernier/Geneva Switzerland.

[3] F.R.FERREGUTTI - SAFETY LABORATORY. 1995. Report No. 1915-FRF.

[4] Kamienski FX, Casida E. Importance of demethylenation in the metabolism in vivo and in vitro of methylenedioxyphenyl synergists and related compounds in mammals. Biochem Pharmacol 1970;19:91-112.

[5] Klungsoyr J, Scheline RR. Metabolism of piperonal and piperonyl alcohol in the rat with special reference to the scission of the methylenedioxy group. Acta Pharm Suec. 1984;21:67-72.

[6] Dahl AR. The inhibition of rat nasal cytochrome p-450-dependent mono-oxygenase by the essence heliotropin (piperonal). Drug Metab Dispos. 1982;10:553-554.