1,3-dioxepane

Endpoint summary

Additional information

Unfortunately no experimental data regarding toxikocinetics of 1,3-dioxepane exists.

There is no specific requirement to generate TK information in REACh. Annex I, Section 1.0.2 states that “the human health hazard assessment shall consider the toxicokinetic profile (i.e. absorption, metabolism, distribution and elimination) of the substance”. Furthermore, REACh announces in Annex VIII (Section 8.8.1) that one should perform “assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information”.

 

Absorbtion

Oral

From the molecular weight of 102.13 g/mol, the log Pow of 0.6 (at 20 °C) and a good water solubility of 263 g/l (at 20°C) a considerable absorption of dioxepane in the GI-tract can be anticipated.

Inhalation

At room temperature 1,3 -dioxepane in a liquid and based on the vapor pressure of 20 hPa at 18.5°C a significant vapor exposure needs to be taken into account.

Based on the already mentioned physico-chemical properties of dioxepane (molecular weight of 102.13 g/mol, log Pow of 0.6 and water solubility of 263 g/l) a considerable absorption can also be anticipated for the inhaled vapor in the respiratory tract. Furthermore water soluble vapors like dioxepane can be effectively removed from the air in the upper respiratory tract.

Dermal

Dermal absorption represents the amount of topically applied substance that is found in the epidermis (stratum corneum excluded) and in the dermis, and this quantity is therefore taken as systemically available. Again, based on the physico-chemical properties of dioxepane (molecular weight of 102.13 g/mol, log Pow of 0.6 and water solubility of 263 g/l) a considerable dermal absorption can not be excluded, even tough an in silico prediction (DERMWIN v2.00) resulted in a dermal permeability coefficient (Kp) of 0.00105 cm/hr, indicating a low dermal uptake.

Based on the high vapor pressure of dioxepane (20 hPa at 18.5°C), the extend of the vapor partitioning from the air into the stratum corneum is limited by evaporation. 

 

Accumulative potential

Although there is no direct correlation between the lipophilicity of a substance and its biological half-life, substances with high log P values tend to have longer half-lives unless their large volume of distribution is counter-balanced by a high clearance. On this basis, there is the potential for highly lipophilic substances (log P >4) to accumulate in individuals that are frequently exposed (e.g. daily at work) to that substance. Since for dioxepane the log Pow is 0.6, no significant accumulative potential in adipose tissue needs to be anticipated.

 

Metabolism

In an in vitro assay the formaldehyde-formation out of dioxepane and the fate of formaldehyde was assayed under the conditions of in vitro cytogenicity studies (BASF AG, 1998). Incubations were performed with and without a metabolic activation system (S9-mix). Detectable amounts of formaldehyde were formed in the incubations with S9-mix but not in the absence of S9-mix. A direct extrapolation to the in vivo metabolisation is difficult, but the formation of formaldehyde particularly in metabolicaly active tissues (e.g. the liver) can not be excluded.

 

Excretion

Substances that are excreted in the urine tend to be water-soluble and of low molecular weight. Substances that are excreted in the bile tend to have higher molecular weights. Based on the molecular weight of 102.13 g/mol and a good water solubility of 263 g/l (at 20°C) a predominant excretion via the urine can therefore be anticipated. To a certain extend vapors are likely to be additionally excreted via the exhaled air. Furthermore a low lipid solubility can be derived from the log Pow of 0.6, and therefore no distinct concern for high dioxepane concentrations in the breast milk exists.