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Description of key information

Rosemary oil is expected to be readily absorbed, orally and via inhalation but somewhat less via the dermal route, based on physico-chemical parameters. The substance also is expected to have some dermal absorption but this will be limited due to its log Kow (log kow constituents range from 2.85 to 6.3) and the dermal absorption will not exceed the oral route. As adverse effects were observed in the oral repeated dose study, route-to-route extrapolation will be performed to estimate the dermal and respiratory DNELs.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

Toxicokinetic behaviour of Rosemary oil (CAS 84604-14-8)



Rosemary oil (CAS 84604-14-8) is an UVCB, and is extracted from the leaves, flowers and twigs of Rosmarinus officinalis L. (Lamiaceae) by steam distillation.Rosemary oil is an UVCB containing hydrocarbon type of substances. The main substances contain an ether group (cineol), solely hydrocarbon (alpha-pinene and camphene) or a ketone (camphor).

Rosemary oil is a liquid with a melting point of <-20°C and a boiling point of 158 – 210 °C. It’s known constituents have a molecular weight range of 136.24 - 204.36, that does not preclude absorption. The volatility of the constituents ranges from 0.06 – 536.0 Pa at 25°C.



Oral: In an acute oral toxicity study an LD50 of 5000 mg/kg bw was determined for Rosemary oil. Systemic effects on the Central Nervous System were observed, indicating that absorption through the gut is relevant for Rosemary oil. The relatively low molecular weight range (136.24 – 204.36) would favour absorption through the gut. According to Martinez and Amidon (2002) the optimal log Kow for oral absorption falls within a range of 2-7. The Log Kow of the constituents ranges from 2.85 – 6.3. Furthermore, the water solubility of the main constituents of this UVCB (1.97 – 3500 mg/L)(Cineole, Alphapinene, Camphor, Beta pinene, Camphene) indicate that parts of this UVCB can be absorbed in the GI tract via passage through aqueous pores or carriage of such molecules across membranes with the bulk passage of water (Renwick, 1994). Micellar solubilisation may be of particular importance for the constituents that are highly lipophilic. Based on these observations, oral absorption is expected. Therefore the default absorption percentage of 50%will be used.


Skin: Based on the molecular weight, log Kow and water solubility it is likely that the substance will show some dermal absorption. The optimal molecular weight and log Kow for dermal absorption is <100 and in the range of 1-4, respectively (ECHA guidance, 7.12, Table R.7.12-3). The molecular weight range of the substance is somewhat outside of the optimal range and therefore skin absorption is expected, though the extent is difficult to estimate. Skin irritation was observed in Rabbits exposed to 10 mL/kg bw.This suggests that this UVCB may damage the skin and thereby increase its penetrating potential.The skin absorption will not exceed oral absorption and therefore the default percentage of 50% dermal absorption will be used.


Lungs:The inhalation exposure route is thought to be of relevance because of the volatility of the main constituents ranging from 87 - 633 Pa at 25°C (cineole, alpha-pinene, camphor, beta-pinene, camphene). The average vapour pressure for Rosemary oil was determined to be 225 Pa based on all its constituents. Its octanol/water partition coefficient range does indicate that inhalation absorption is possible when the substance reaches the lungs.The blood/air (B/A) partition coefficient is another partition coefficient indicating lung absorption. Buist et al. 2012 have developed B/A portioning model for humans using the most important and readily available parameters:

Log PBA = 6.96 – 1.04 (Log VP) – 0.533 (Log Kow) – 0.00495 MW.

For Rosemary oil the B/A partition coefficient, calculated with the average VP, log Kow and MW values would result in:

Log P (BA) = 6.96 – 1.04 x (2.35) – 0.533 x (3.8) – 0.00495 x 150.07= 1.75

This means that Rosemary oil has a tendency to go from air into the blood. The B/A partition coefficient indicates that the substance can be readily absorbed via the inhalation route. Based on this, inhalation absorption of 100% will be assumed.



The water solubility (1.97 – 3500 mg/L) of the constituents as well as its log Kow range (2.85 – 6.3), indicates that the substance is likely to pass through the biological cell membrane and distribute into cells, the intracellular concentration may be higher than extracellular for the concentration particularly in fatty tissues. For this UVCB, the constituents with a log Kow around 4 or higher may have some potential to build-up within the body, depending on their biological half-life.



In a OECD TG 422 study conducted with the read-across source substance Eucalyptus oil, effects on the livers of the treated rats were observed, indicating metabolism in the liver. Minimal centrilobular hepatocytic hypertrophy of the male livers was observed and associated with liver weight increase. These findings were considered an adaptive change likely associated with microsomal enzyme induction. Furthermore, the alpha-hydrocarbon nephropathy seen in male rats is indicative for metabolism in the liver lysosomes and transport of the substances via alpha-2µglobulins.

During Phase I metabolism, constituents with methyl groups outside the skeleton of the backbone can become oxidised into primary alcohols and subsequently acids (1,8 Cineole, Alpha-Pinene, Camphene, Beta-Pinene). Cineol is one of the common constituents that will be reduced into a tertiary alcohol and is likely a metabolite that will be distributed by alpha-2µglobulins.



The kidney is the expected to be the main route of excretion, based on the renal effects observed in the repeated dose study performed in rats receiving theread-acrosssource substance Eucaplyptus oil. Hyaline droplet nephropathy in the kidneys of exposed male rats is caused by accumulation ofalpha-2µglobulins(produced by the male rat liver) in the proximal tubules. These effects support that the kidney is the main route of excretion.


Bioaccumulation:For this UVCB, constituents with a log Kow around 4 or higher may have some potential for bioaccumulation, depending on their biological half-life.



Rosemary oil is expected to be readily absorbed, orally as well as after inhalation, based on the oral absorption information, human toxicological information and physico-chemical parameters. As adverse effects were observed in an oral repeated dose study, route-to-route extrapolation will be performed to estimate the dermal and inhalatory no effect levels.

Oral to dermal extrapolation:The critical toxic property of Rosemary oil is related to systemic effects and therefore route-to-route extrapolation is applicable. The toxicity of the substance can be due to the parent constituents but also to its metabolites. The overriding principle will be to avoid situations where the extrapolation of data would underestimate toxicity resulting from human exposure to a chemical by the route-to-route extrapolation. The absorption will be slower via the skin. Therefore it will be assumed that the oral absorption will be equal to dermal absorption. Using the asymmetric handling of uncertainty the oral absorption will be considered 50% and the dermal absorption will be considered also 50%.

Oral to inhalation extrapolation:Rosemary oil has an average vapour pressure of 225 Pa therefore inhalation exposure is considered to be relevant. The substance is expected to be readily absorbed via the inhalation route. In the absence of bioavailability data it is most precautionary that 100% of the inhaled vapour becomes bioavailable. For the oral route, 50% absorption will be used for route-to-route extrapolation to be precautionary for the dermal route.For inhalation absorption 100% will be used for route-to-route extrapolation.



Rosemary oil is expected to be readily absorbed via the inhalation and oral route, and somewhat slower via the dermal route. Using the precautionary principle for route-to-route extrapolation the final absorption percentages derived are: 100% inhalation absorption, 50% oral absorption and 50% dermal absorption.



- Martinez, M.N., And Amidon, G.L., 2002, Mechanistic approach to understanding the factors affecting drug absorption: a review of fundament, J. Clinical Pharmacol., 42, 620-643.

- Buist, H.E., Wit-Bos de, L., Bouwman, T., Vaes, W.H.J., 2012, Predicting blood:air partition coefficient using basic physico-chemical properties, Regul. Toxicol. Pharmacol., 62, 23-28. 

- IGHRC, 2006, Guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals,[1].pdf