Hexane, 1,6-diisocyanato, homopolymer, N-butyl-1-butanamine-blocked

Endpoint summary

Description of key information

Based on the physicochemical properties, systemic availability of the UVCB substance may be limited but cannot be completely excluded following oral intake. Considering the low vapour pressure no relevant amounts of the UVCB substance are expected to be inhalable under normal use conditions. Also based on the physicochemical properties uptake of the UVCB substance into the systemic circulation following dermal exposure is very limited, if taken place at all. Due to the low vapour pressure, it is unlikely that relevant amounts of the reaction mass will become systemically bioavailable via inhalation. 
Following oral intake, it is expected that the majority of the chemical is excreted with the faeces. For any amounts potentially being bioavailable, it is assumed that circulation within the blood stream and subsequent metabolism may occur. Ultimately, absorbed amounts are expected to be excreted with the faeces or, to a lesser extend, in the urine depending on the molecular size. It is expected that the substance has no potential for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

1 Physicochemical Data on Hexamethylene diisocyanate, oligomers, blocked with dibutylamine

The UVCB substance Hexamethylene diisocyanate, oligomers, blocked with dibutylamine appears as a highly viscous,clear and colourless liquidat standard ambient temperature and pressure. The molecular weight of the UVCB substance depends on the degree of polymerisation and is expected to be considerably higher than 500 g/mol. The UVCBsubstance has a very low vapour pressure of 1x 10^-4Pa at 20°C which can be regarded as negligible for the present assessment. The substance has a low water solubilityas the water solubility value falls in the range of 2 to 4 mg/L. For all componentsthe LogPow value is estimated to be below 3.Hydrolysis of the UCVB substance is not expected based on the chemical structure.

 

 

2 Toxicokinetic Analysis ofHexamethylene diisocyanate, oligomers, blocked with dibutylamine

 

Absorption

 

Oral route:

In order to be absorbed into the systemic circulation, chemicals have to dissolve into the gastro-intestinal (GI) fluids and make contact with the mucosal surface. Hence, the poor water solubility of the UVCB substance may drastically reduce the amount available for uptake into the systemic circulation.

Moreover, the molecular weight of the reaction products is expected to be considerably above 500 g/mol and thus, does not favour absorption into the systemic circulation via the GI tract.With regards to toxicological data, an acute oral systemic toxicity studies in rats (OECD 423) conducted with the UVCB substance determined the respective LD50 value to be greater than 2000 mg/kg (limit dose) with no local or systemic effects noted. Furthermore, a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats (OECD 422) was conducted on the substance. No adverse effects were observed in the parental animals and the offspring. Thus, the NOAEL for general, reproductive and developmental toxicity was determined to be 1000 mg/kgbw/day (limit dose).

Overall,with regard to the physicochemical properties and theabsence of systemic effects in the toxicological investigation, it is unlikely that relevant amounts ofthe UVCB substancewill reach the systemic circulation. Even if certain amounts become bioavailable no systemic toxicity is expected.

Dermal route:

The physicochemical properties of the UVCB substance such as molecular weight and water solubility, will drastically limit the amount available for dermal absorption.

Again, the assumption that dermal absorption is limited is further strengthened by the results achieved from the dermal toxicity testing. In an acute dermal toxicity study (OECD 402), the substance didnot cause any local or systemic effects and the LD50 was determined to be greater than the limit dose (2000 mg/kg bw). Furthermore, no indication of systemic absorption was evident with respect to the results obtained from a Local Lymph Node Assay (LLNA, OECD 429) assay conducted on mice. Here, no immunological response was triggered and no signs of systemic toxicity were present.

Overall, the physicochemical properties and the findings from the dermal toxicity studysupport that absorption into the systemic circulation is expected to be low, if even taken place at all, after dermal application.

 

Inhalation route:

Considering the low vapour pressure and the resulting low volatility, it is unlikely that the UVCB substance will become bioavailable via inhalation when handled at ambient temperature.

 

Distribution

 

With regards to the physicochemical properties and the results achieved from the comprehensive toxicity testing, it appears that the bioavailability ofthe UVCB substancevia the main entrance routes (i.e., oral, dermal and through inhalation) is limited but cannot be excluded. If any amounts of the UVCB become systemically available, they will be most likely transported within the body via the blood stream. Due to the absence of systemic effects in the oral toxicity studies, there are no hints with regard to any potential target organ.

 

Metabolism

 

Because absorption of the UVCB substance into the interior part of the body cells is considered to be limited, considerable contact of the substance with intracellular metabolising enzymes is unlikely. However, in the event that fractions of the UVCB substance reach the systemic circulation it cannot be ruled out that they are metabolised by Phase I enzymes while undergoing functionalisation reactions aiming to increase their hydrophilicity. Furthermore, Phase II conjugation reactions may covalently link an endogenous substrate to the chemicals or its Phase I metabolites in order to ultimately facilitate excretion.

 

Excretion

 

As mentioned before, it is expected that the bioavailability of the UVCB substance is most likely to be limited and distribution into the body will be low. Thus it is expected that following oral ingestion the vast majority of the chemicals is excreted with the faeces. However, even if a certain amount of the reaction product is absorbed, this will most likely be excreted via the faeces as well due to the molecular size. For smaller degradation or break down products, resulting from metabolism processes, excretion via the urine might also be possible. Moreover, with regard to the substance’s LogPow value, the potential for bioaccumulation is expected to be negligible.

 

3 Summary

 

Based on the physicochemical properties, systemic availability of the UVCB substance may be limited but cannot be completely excluded following oral intake. Considering the low vapour pressure no relevant amounts of the UVCB substance are expected to be inhalable under normal use conditions. Also based on the physicochemical properties uptake of the UVCB substance into the systemic circulation following dermal exposure is very limited, if taken place at all. Due to the low vapour pressure, it is unlikely that relevant amounts of the reaction mass will become systemically bioavailable via inhalation.

Following oral intake, it is expected that the majority of the chemical is excreted with thefaeces. For any amounts potentially being bioavailable, it is assumed that circulation within the blood stream and subsequent metabolism may occur. Ultimately, absorbed amounts are expected to be excreted with the faeces or, to a lesser extend, in the urine depending on the molecular size. It is expected that the substance has no potential for bioaccumulation.

 

 

4 References

 

Bonse G., Metzler M. (1978) Biotransformation organischer Fremdsubstanzen.Thieme Verlag, Stuttgart.

 

ECHA (2008) Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.

 

Marquardt H., Schäfer S. (2004) Toxicology.Academic Press, San Diego, USA, 2nd Edition 688-689.

 

Mutschler E., Schäfer-Korting M. (2001) Arzneimittelwirkungen. Lehrbuch der Pharmakologie und Toxikologie. Wissenschaftliche Verlagsgesellschaft, Stuttgart.

 

Renwick A.G. (1994) Toxicokinetics - pharmacokinetics in toxicology.In Hayes,A.W. (ed.)

Principles and Methods of Toxicology. Raven Press, New York, p 103.

 

Rozman K.K., Klaassen C.D. (1996) Absorption, Distribution, and Excretion of Toxicants.In Klaassen C.D. (ed.) Cassarett and Doull's Toxicology: The Basic Science of Poisons.McGraw-Hill, New York.