Registration Dossier
Registration Dossier
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EC number: 230-597-5 | CAS number: 7212-44-4
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
Limited toxicokinetic data are available for nerolidol.
Nerolidol has a molecular weight of 222 g/mol and is a liquid with a low volatility (0.24 Pa at 20°C). It is highly lipophilic with a logPow of 4.5 (at 24°C) and shows a low water solubility (14.1 mg/l at 20°C).
In a reproductive screening study in rats, repeated administration of nerolidol via the diet at 0, 1500, 4000, 12000 ppm resulted in general systemic adverse effects on body weights and the liver, providing evidence for bioavailability of nerolidol via the oral route (BASF 96R0466/09052).
In support, a study on the structually similar substance linalool (CAS 78-70-7), provides evidence for a rapid and complete absorption in rats after oral administration. Labelled linalool (14C) was administered orally (gavage, 500 mg/kg bw) and intraperitoneally (20 mg/animal) to male Wistar rats (Parke 1974). After oral adminsitration, the majority was excreted via urine (60% of administered radioactivity), expired air (23%) and faeces (15%) 72 hours after application, whereas only 3% of the dose were detected in tissues, i.e. brain, lung, liver, heart, spleen, gastro-intestinal tract, kidney, skin and skeletal muscle. Intraperitoneal administration with a subsequent collection of bile revealed, that approx. 25% of the dosed linalool is excreted via the bile probably by formation of respective glucuronide and sulfate conjugates. Transfer of the bile from a linalool treated animal into the duodenum of an untreated animal further indicated the occurrence of enterohepatic circulation.
Taken together, oral absorption is to be expected at a hight rate based on the low molecular weight and the findings from the structurally related linalool.
When considering the vapour pressure of nerolidol, limited adsorption of the substance via the inhalative route can be assumed. In a standardized inhalation hazard test using a saturated vapour atmosphere with trans-nerolidol (CAS 40716-66-3), no mortality, clinical signs or pathological findings were seen after a 7 h exposure (BASF 10I0193/877088). Due to the low volatility of the substance, the mean concentration of the test material during 7 h exposure was not determinable by weighing.
No experimental data on the capacity of dermal absorption of nerolidol are avaialble, however, on the basis of the given physicochemical parameters, i.e. high log Pow and a low water solubility, dermal absorption into viable skin layers is considered to be low and a low bioavailability via the the dermal route is therefore to be expected. No acute toxicity has been reported after single dermal application of nerolidol (Russel 1973), which could stem from the absence of a toxic potential of nerolidol and/or the absence of bioavailablility via the dermal route.
Only limited information is available in terms of metabolism of nerolidol.
One study was conducted to investigate the effect of the test material on the activities of the hepatic drug metabolizing enzymes (Parke 1969). It was found that nerolidol produced no increase in the activities of biphenyl 4-hydroxylase, glucuronyl transferase or cytochrome P-450, but increased the activity of 4-nitrobenzoate reductase by 25-50%.
Nerolidol was found to be negative in an Ames Test, indicating no reactivity of nerolidol or its metabolites.
Taken together, a potential for bioaccumulation of nerolidol is considered to be unlikely.
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