Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - dermal (%):
50

Additional information

The physicochemical properties of 7-hydroxycitronellal, i.e. small molecular weight, LogPow and high water solubility at room temperature (MW = 172.26, Log POW= 1.68, water solubility = 35 g/L), indicate a good bioavailability of the substance via the oral route.

Dermal absorption of 7-hydroxycitronellal was evaluated using [14C]-labeled hydroxycitronellal and full-thickness dorsal rat skin in an in vitro flow-through diffusion cell system (Tonge, 1995). Receptor fluid, dry lint swabs, tape-strips, teflon cell body and cap and remaining skin were assessed for the content of hydroxycitronellal in different experimental setups.

1) The absorption of neat HC through full-thickness rat skin and the effect of the vehicle (ethanol and ethanol:DEP) on the absorption was investigated.

2) Skin samples after stratum corneum removal were compared to intact skin samples on the absorption of HC.

3) ) Skin samples after stratum corneum and epidermis removal were compared to intact skin samples on the absorption of HC.

4) Distribution of HC between different layers of rat skin was investigated on intact skin samples.

HC distribution in different skin layers was reported to be approx. 5% of the applied dose in SC and approx. 10% of the applied dose in tape-stripped skin within the observation period of 6 hours. According to these data, 1/3 of the HC levels found in skin are estimated to be located in the SC and 2/3 in epidermis and dermis.

Application of neat HC and HC in different vehicles resulted in calculated sums (% dose of receptor fluid + intact skin) between 60% and 64%. For all vehicles examined, no significant differences in the absorption of HC though rat skin were observed. No determination of HC levels in the stratum corneum was performed in this experimental setup, however, considering the ratio of HC found in the skin layer distribution study, the bioavailable amount of HC, i.e. levels in receptor fluid, dermis and epidermis was estimated to be approx. 50 % of the applied dose or lower.

Compared to full-thickness skin, removal of the stratum corneum resulted in a 3-fold increase and removal of the stratum corneum and epidermis resulted in a 4-fold increase in the total amount of HC traversing the skin in 72 hours. These findings demonstrate the relevance of these skin layers as barrier.

Although human skin is described to result in lower skin penetration levels than rat skin, the estimated 50% bioavailability via the dermal route has been taken for the respective DNEL derivation as a worst case.

 

On the basis of the low vapour pressure at room temperature (vapour pressure = 0.54 Pa), it can be assumed that the exposure via inhalation of 7-hydroxycitronellal as a vapour is low.

Based on a pharmacokinetic study in rabbits, oral administration of hydroxycitronellal resulted in detectable amounts of hydroxycitronellol and hydroxycitronellic acid in ß-glucuronidase/arylsulfatase treated urine. Therefore a reduction to yield the corresponding alcohol and an oxidization to yield the corresponding carboxylic acid is evident and a subsequent conjugation with e.g. glucuronide is to be expected (Ishida et al., 1989). Furthermore, incubation of hydroxycitronellal in human skin homogenate or on intact full-thickness and dermatomed rat (excl. SC and epidermis) skin in a flow-through diffusion cell system resulted in the formation of hydroxycitronellol and hydroxycitronellic acid but no evidence for the presence of glucuronide or sulfate conjugates were given (Tonge, 1995).

Based on the information given above, there is no evidence for a bioaccumulative potential of 7-hydroxycitronellal.