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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Endpoint:
basic toxicokinetics, other
Type of information:
other: expert statement based on analysis of all available information
Adequacy of study:
key study
Study period:
March 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: expert statement based on analysis of all available information

Data source

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Expert statement based on the analysis of all available information on the substance, including physico-chemical properties and the results of toxicological studies.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Oxacycloheptadecan-2-one
EC Number:
203-662-0
EC Name:
Oxacycloheptadecan-2-one
Cas Number:
109-29-5
Molecular formula:
C16H30O2
IUPAC Name:
oxacycloheptadecan-2-one
Radiolabelling:
no

Test animals

Species:
other: not applicable, toxicokinetic assessment

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
For risk assessment purposes, 10% absorption will be considered for all exposure routes.
Type:
distribution
Results:
Based on physico-chemical properties, accumulation in adipose tissue is possible. Based on very low solubility of the substance, its distribution in the body is unlikely.
Type:
metabolism
Results:
Toxtree v.2.6.13 predicts metabolism by aliphatic hydroxylation of primarily alpha-position of lactone moiety.
Type:
excretion
Results:
Based on physico-chemical properties, the main route of excretion is expected to be via faeces.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The physico-chemical properties of the substance, in particular its very low water solubility and high log Kow (4-7.3), suggest that its absorption from gastrointestinal tract will be limited. This is in agreement with the results of available toxicity studies, in which the substance was not acutely toxic by oral route up to and including dose level of 5000 mg/kg bw, and the results of the OECD guideline 422 study, in which no adverse effects or clinical signs of toxicity were seen at the highest dose level of 1000 mg/kg bw/day. Based on this, the value for oral absorption is set at 10%.
Although the substance has a high log Kow (range 4-7.3, the main constituent has most probably log Kow of 7.3), its molecular weight (254.41 g/mol) is below the cut-off value of 500 g/mol, when dermal absorption of 10% can be considered. However, considering very low water solubility of the substance, the lack of any adverse findings in the available repeated dose toxicity study and the fact that, in general, dermal absorption will not be higher than oral absorption, value of 10% will be considered for dermal absorption.
Oxacycloheptadecan-2-one is an opaque crystalline mass, without fine particles, under ambient conditions. Its vapour pressure is very low (<= 0.028 Pa). Therefore it is not likely that the substance will reach the nasopharyncheal region or subsequently the tracheo/bronchial/pulmonary region via inhalation of vapor or fine particles. If the substance reaches the tracheobronchial region, it is not likely to diffuse/dissolve into the mucus lining of the respiratory tract as it does not dissolve in water and its log Pow >7; hence, absorption is expected to be limited. Based on the above data, for risk assessment purposes the inhalation absorption of oxacycloheptadecan-2-one is set at 10%.
Details on distribution in tissues:
Once absorbed, distribution of the test substance throughout the body is not expected based on its very low water solubility. Based on a limited distribution throughout the body but high partition coefficient the substance is expected to accumulate limitedly in adipose tissue.
Details on excretion:
Based on very low solubility and high log Kow of oxacycloheptadecan-2-one, the main route of excretion will probably be via faeces.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
There is no evidence suggesting that the substance is metabolized in the body. The lack of adverse findings or clinical signs of toxicity in the available OECD guideline 422 study together with its physico-chemical properties suggest that the substance is probably poorly absorbed. Nevertheless, the metabolism of oxacycloheptadecan-2-one by CYP450 was predicted using Toxtree v 2.6.13. The primary metabolic pathway is considered to be aliphatic hydroxylation of the CH2 group in the alpha position to lactone moiety. As a secondary pathway, aliphatic hydroxylation at C9 or C10 position of the ring is predicted by Toxtree v 2.6.13.

Applicant's summary and conclusion

Conclusions:
The toxicokinetic assessment for oxacycloheptadecan-2-one was performed based on all available data. For risk assessment purposes, 10% absorption will be considered for all exposure routes. Once absorbed, distribution of the test substance throughout the body is not expected based on its very low water solubility. Based on a limited distribution throughout the body but high partition coefficient the substance is expected to accumulate limitedly in adipose tissue. The main route of excretion will probably be via faeces.
Executive summary:

The toxicokinetic assessment for oxacycloheptadecan-2-one was performed based on all available data. In the available 28-day study with the reproductive and developmental toxicity screening no adverse effects or clinical signs of toxicity were observed at the highest tested dose of 1000 mg/kg bw/day. The substance is practically insoluble in water (water solubility 0.103 mg/L) and has a very high log Kow (range 4.0 -7.3). This in combination with the results of the available repeated dose study suggest that its absorption from gastrointestinal tract will be limited. For risk assessment purposes, 10% oral absorption will be considered in the lack of other data. Considering very low water solubility of the substance, its high log Pow and the fact that, in general, dermal absorption will not be higher than oral absorption, value of 10% will be considered for dermal absorption. Oxacycloheptadecan-2 -one is an opaque crystalline mass, without fine particles, under ambient conditions. Its vapour pressure is very low (<= 0.028 Pa). Therefore it is not likely that the substance will reach the nasopharyncheal region or subsequently the tracheo/bronchial/pulmonary region via inhalation of vapor or fine particles. If the substance reaches the tracheobronchial region, it is not likely to diffuse/dissolve into the mucus lining of the respiratory tract as it does not dissolve in water and its log Pow >7; hence, absorption is expected to be limited. Based on the above data, for risk assessment purposes the inhalation absorption of oxacycloheptadecan-2-one is set at 10%. Once absorbed, distribution of the test substance throughout the body is not expected based on its very low water solubility. Based on a limited distribution throughout the body but high partition coefficient the substance is expected to accumulate limitedly in adipose tissue. Considering very low water solubility and high log Pow of oxacycloheptadecan-2 -one, the main route of excretion is expected to be via faeces.