Cyclohexadecen-1-one

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Expert Statement

Type of information:

other: Expert Statement

Adequacy of study:

key study

Study period:

2019-02-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert statement, no other study available

Data source

Reference

Reference Type:

other: Expert Statement

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Principles of method if other than guideline:

Expert Statement

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

448-300-4

EC Name:

-

Cas Number:

88642-03-9

Molecular formula:

C16H28O

IUPAC Name:

(6E)-cyclohexadec-6-en-1-one; (7Z)-cyclohexadec-7-en-1-one; (8E)-cyclohexadec-8-en-1-one; (8Z)-cyclohexadec-8-en-1-one

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Inhalation
The low water solubility (<1 mg/L) and high lipophilicity (log Pow = 6.5) indicate that the substance may be retained in the mucus and indicates a potential for accumulation. However, due to the low volatility (vapour pressure = 0.0092 Pa) and the susceptibility to convert to the molten state in view of the very low melting point (= 25°C) tendency, the potential for inhalation of dust or vapours is only marginal.

Oral
The test item has a low water solubility (<1 mg/L) and is highly lipophilic, and therefore may not readily dissolve in gastrointestinal fluid and absorption by passive diffusion will be very limited. Furthermore, no toxicity was observed in the acute oral toxicity study and in the subchronic oral toxicity study up to 1000 mg/kg bw. Systemic absorption does not seem to be a preferential route of entry into the body.

Dermal
Due to the low water solubility (<1 mg/L) and a logPow of 5.8, dermal uptake is likely to be low. Since the substance is a skin irritant, damage to the skin surface may enhance penetration. However, the lack of toxicity in the acute dermal toxicity study up to a dose of 2000 mg/kg bw may be seen as an indication that this is not a preferential route of entry into the body.

Details on distribution in tissues:

During the 28-day oral toxicity study in the rat only marginal changes in cholesterol levels and liver weights were observed, which indicate that the liver can be considered as target organ. However, the histopathological examination revealed no changes on cellular level. The results of the examinations indicate that following the repeated administration of high doses sufficient amounts are resorbed, as indicated by the marginal reaction of the liver. Apart from that, no signs of systemic toxicity could be observed.

Details on excretion:

The available data do not allow the prediction of an expected metabolism or excretion of the substance.

Metabolite characterisation studies

Details on metabolites:

It can be assumed that P450-enzymes are substantially involved in the metabolism of the test item, since in the chromosome aberration test with human lymphocytes clear toxic effects were observed after 4 h and 22h treatment with 49 µg/mL and above in the absence of S9 mix, whereas no cytotoxic effects could be observed after 4h treatment up to the highest applied concentration in the presence of S9 mix. The available data do not allow the prediction of an expected metabolism or excretion of the substance. Metabolism by Phase I enzymes, such as CYP450 enzymes, usually aims to enhance hydrophilicity of the substance by for example hydroxylation. Thus, the test item is not considered of concern in regards to bioaccumulation, since it is anticipated that it is metabolised to more hydrophilic metabolites in the organism.