Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Expert statement
Adequacy of study:
weight of evidence
Study period:
2019
Reliability:
other: not relevant for expert statement

Data source

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Expert statement
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous

Results and discussion

Main ADME results
Type:
absorption
Results:
100% (oral), 10% (inhalation), 15% (dermal)

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Oral :
After oral administration, a compound needs to be dissolved before it can be taken up from
the gastrointestinal tract1. Since the water solubility of Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is high
(> 1000 g/L), the substance is expected to be totally dissolved in gastrointestinal fluids,therefore the availability for uptake is expected to be high. Based on its moderate molecular weight (242-386), uptake via passive diffusion might occur, but might be too big for passage through aqueous pores or carriage across membranes with the bulk passage of water. Tetradecafluorohexane has a relatively low partition coefficient (log Pow < 4.5), which is considered favourable for passive diffusion, and thus high absorption. The substance have ionisable groups that could influence its absorption. However, as the substance is acid, thus gastric acid is not expected to modify the ionisation form nor the absorption.
For risk assessment purposes, oral absorption of Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is set at 100%, based on its high water solubility, moderate molecular weight and low log Pow. The oral toxicity data do not provide reasons to deviate from the proposed oral absorption factor2.

Respiratory :
Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine has high water solubility, so its dissolution in mucus lining in the respiratory tract may be high. Moreover, Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine has a low partition coefficient (log Pow < 4.5), which is considered favourable for passive diffusion through biological membranes. However, Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine has a very low vapour pressure (2.07 x 10-4 Pa at 20 °C ), which indicates that Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is not volatile and exposure by inhalation is not expected. A very limited amount of vapours, not lipophilic (log Pow < 4) does not have the ability to reach the deep lung, thus absorption through gas exchange may only marginally occur.
Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is a liquid, which indicates that exposure via areosols is also possible.
Aerosols can reach the tracheobronquial region of the respiratory tract. Taking in consideration all these factors together, it is concluded that for risk assessment purposes, the inhalation absorption should be set at 10%2.

Dermal :
Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is a liquid with high water solubility, it will dissolve
into the surface moisture of the skin to allow uptake. The relatively low logPow (<4) indicates the crossing of epidermal barriers will occur. According to the criteria given in the REACH Guidance2, a default value of 100% dermal absorption has been established if the molecular weight is lower than 500 and log P between -1 and 4. The physical/chemical properties of Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine fully meet the criteria for full dermal absorption (MW 242-386; log Pow <4.5).
Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine skin corrosive, so enhanced uptake related to local effects is expected, but skin contact is not expected and may be very limited in time. Acute dermal toxicity study did not show mortality at 2000 mg/kg. As mortality was observed form 300 mg/kg by oral route, it can be concluded that dermal absorption is lower than 15 %. For risk assessment purpose, as a conservative hypothesis, dermal absorption is set at 15%.

Applicant's summary and conclusion

Conclusions:
A toxicokinetic assessment was performed based on the available data of the substance.
Based on the physical/chemical properties of the substance, absorption factors for this
substance arederived to be 100% (oral), 10% (inhalation) and 15% (dermal) for risk
assessment purposes. The bioaccumulation potential is expected to be low.
Executive summary:

A substance can enter the body via de gastrointestinal tract, the lungs, and the skin1. Since

different parameters are relevant for absorption via the different routes of exposure, the

uptake via these three routes will be addressed individually.

 

Oral :

After oral administration, a compound needs to be dissolved before it can be taken up from

the gastrointestinal tract1. Since the water solubility of Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is high

(> 1000 g/L), the substance is expected to be totally dissolved in gastrointestinal fluids,therefore the availability for uptake is expected to be high. Based on its moderate molecular weight (242-386), uptake via passive diffusion might occur, but might be too big for passage through aqueous pores or carriage across membranes with the bulk passage of water. Tetradecafluorohexane has a relatively low partition coefficient (log Pow < 4.5), which is considered favourable for passive diffusion, and thus high absorption. The substance have ionisable groups that could influence its absorption. However, as the substance is acid, thus gastric acid is not expected to modify the ionisation form nor the absorption.

For risk assessment purposes, oral absorption of Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is set at 100%, based on its high water solubility, moderate molecular weight and low log Pow. The oral toxicity data do not provide reasons to deviate from the proposed oral absorption factor2.

 

Respiratory :

Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine has high water solubility, so its dissolution in mucus lining in the respiratory tract may be high. Moreover, Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine has a low partition coefficient (log Pow < 4.5), which is considered favourable for passive diffusion through biological membranes. However, Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine has a very low vapour pressure (2.07 x 10-4 Pa at 20 °C ), which indicates that Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is not volatile and exposure by inhalation is not expected. A very limited amount of vapours, not lipophilic (log Pow < 4) does not have the ability to reach the deep lung, thus absorption through gas exchange may only marginally occur.

Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is a liquid, which indicates that exposure via areosols is also possible.

Aerosols can reach the tracheobronquial region of the respiratory tract. Taking in consideration all these factors together, it is concluded that for risk assessment purposes, the inhalation absorption should be set at 10%2.

 

Dermal :

Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is a liquid with high water solubility, it will dissolve

into the surface moisture of the skin to allow uptake. The relatively low logPow (<4) indicates the crossing of epidermal barriers will occur. According to the criteria given in the REACH Guidance2, a default value of 100% dermal absorption has been established if the molecular weight is lower than 500 and log P between -1 and 4. The physical/chemical properties of Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine fully meet the criteria for full dermal absorption (MW 242-386; log Pow <4.5).

Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine skin corrosive, so enhanced uptake related to local effects is expected, but skin contact is not expected and may be very limited in time. Acute dermal toxicity study did not show mortality at 2000 mg/kg. As mortality was observed form 300 mg/kg by oral route, it can be concluded that dermal absorption is lower than 15 %. For risk assessment purpose, as a conservative hypothesis, dermal absorption is set at 15%.

 

Once absorbed, distribution of the substance throughout the body is expected to be high

based on its high water solubility, relatively low log Pow and moderate molecular

weight. Orally absorbed Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine may be metabolized in the gastrointestinal tract or the liver and excreted through bile and urine. Based on its relatively low partition coefficient (log Pow < 4.5), Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is not expected to accumulate in adipose tissue (intracellular concentration may not be higher than the extracellular concentration). The overall bioaccumulation potential of Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine is expected to be low.

 

CONCLUSION

A toxicokinetic assessment was performed based on the available data of the substance.

Based on the physical/chemical properties of the substance, absorption factors for this

substance arederived to be 100% (oral), 10% (inhalation) and 15% (dermal) for risk

assessment purposes. The bioaccumulation potential is expected to be low.