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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

No experimental toxico-kinetic data are available for assessing absorption, distribution, metabolism and excretion of the test substance via the oral and inhalation route. Dermal absorption data are available and resulted in 36.4% absorption. Based on effects seen in the human health toxicity studies and physico-chemical parameters the test substance is expected to be readily absorbed via the oral and inhalation route. The absorption is somewhat lower via the dermal route as is also seen in the experimental study. Using the precautionary principle for route to route extrapolation the final absorption percentages derived are: 50% oral absorption, 36.4% dermal absorption and 100% inhalation absorption.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information


The test substance contains a cyclohexylring with a double bond to which a straight C5 chain is attached with a branched end and an OH group. At the opposite (para) position an ethylaldehyde is attached to the ring. The substance is a liquid with a molecular weight of 210 that does not preclude absorption. The test material is not likely to hydrolyse. The test material has a very low volatility (0.0055 Pa).


Oral: The results of several repeated dose and reproductive toxicity studies show that the substance is being absorbed by the gastro-intestinal tract following oral administration because gestation length was increased at 100 mg/kg bw in a one-generation study and non-adverse liver effects were seen at 150 mg/kg bw in a 28-day repeated dose study. The relatively low molecular weight (210) and the low octanol/water partition coefficient (Log Kow 2.1) and water solubility (3420 mg/L) would favour absorption through the gut. According to Martinez and Amidon (2002) the optimal log Kow falls within a range of 2 - 7 for oral absorption. This shows that the test substance is likely to be absorbed orally. 

Skin: The substance is not a skin and eye irritant but is a skin sensitizer which indicates that dermal absorption occurs. In an in vitro skin absorption study (OECD TG 428) the maximum dermal absorption was considered to be 36.4 %. In addition, based on the physico-chemical characteristics of the substance, being a liquid, its molecular weight (210), log Kow (2.1) and water solubility (3420 mg/L), indicate that dermal absorption is likely to occur. The optimal MW 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 test substance is outside the optimal range for MW meaning that some limitation of dermal absorption is expected which was confirmed by the in vitro result.

Lungs: Absorption via the lungs is also indicated based on these physicochemical properties. The blood/air (BA) partition coefficient is a parameter indicating lung absorption. Due to the low vapour pressure of the test substance a model for calculating the blood/air partition coefficient according to Buist et al. (2012) is not valid. Based on the good water solubility and low vapour pressure the substance is likely to partition in the water and thus into blood.


The water solubility of 3420 mg/l of the test substance indicates that the distribution in the body will be both via the water channels and via the biological cell membranes as is indicated by the log Kow of 2.1. Due to the expected metabolism, the substance as such would not accumulate in the body fat which is indicated by the low bioaccumulation potential expected from the low log Kow (2.1).


The metabolism of the test substance is assessed using OECD Toolbox 3 liver metabolism simulator and supported by experimental metabolism data of analogues of the test substance as presented by The Flavor and Fragrance High Production Volume Consortia (2008)


The substance is expected to be readily absorbed, orally and via inhalation, based on the human toxicological information and physicochemical parameters. Dermal absorption of the test substance has been tested in an in vitro dermal absorption test (OECD TG 428).

The IGHRC (2006) document of the HSE and mentioned in the ECHA guidance Chapter 8 will be followed to derive absorption values via the oral, dermal and inhalation route.

Oral to dermal extrapolation: There are adequate data via the oral route and the critical toxic effect is related to systemic effects and therefore route to route extrapolation is applicable. The toxicity of the substance will be due to the parent compound 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 test substance is not expected to be metabolised in the gut because it is not an ester and it is hydrolytically stable. Though some first pass effect via the liver may occur the toxicity via the dermal route will not be underestimated because absorption will be slower (as has been shown experimentally) and the compound will also pass the liver. Using the asymmetric handling of uncertainty the oral absorption will be considered 50 % (though likely to be higher) and the dermal absorption will be based on the in vitro experimental study: 36.4 %

Oral to inhalation extrapolation: Though the test substance is not a volatile liquid some inhalation exposure will be calculated. The test substance is not irritant or corrosive for skin and eye and the systemic effect will overrule the effects at the site of contact. In the absence of bioavailability data it is most precautionary that 100 % of the inhaled vapour is bioavailable. For the oral absorption 50% has been 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, because this will be precautionary for the inhalation route.

Conclusion: The test substance is expected to be readily absorbed via the oral and inhalation route based on toxicity and physicochemical data and somewhat lower via the dermal route based on experimental data. Using the precautionary principle for route to route extrapolation the final absorption percentages derived are: 50 % oral absorption, 36.4 % dermal absorption and 100% inhalation absorption.


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

The Flavor and Fragrance High Production Volume Consortia, 2008, Revised Test Plan for HMPCC,

IGHRC, 2003, Guidelines on route to route extrapolation of toxicity data when assessing health risks of chemicals,[1].pdf

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.