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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: toxicokinetic assessment
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: toxicokinetic assessment based on physicochemical data and available studies.

Data source

Reference
Reference Type:
other: assessment report
Title:
Unnamed
Year:
2013

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information, EC 2006/1907, Annex VII, 8.8.1

Test material

Constituent 1
Reference substance name:
Sodium Benzotriazolate
Cas Number:
15217-42-2
Molecular formula:
C6H4N3Na
IUPAC Name:
Sodium Benzotriazolate

Results and discussion

Any other information on results incl. tables

Data from in vivo studies, which were designed to identify the toxicokinetic properties of the substance, are not available. One in vitro study on the metabolism of Benzotriazole, the conjugated acid, is available (H. Hoffman et al.: Biotransformation von 1H-Benzotriazol und N-1-Alkylbenzotriazolen in vitroArchiv der Pharmazie, 315, 422-428 (1982)).

This means, that absorption, distribution, metabolism and excretion (ADME) can only be derived from available physical-chemical data and in the case of metabolism additionally from the available study.

To estimate the toxicokinetic properties of the substance the following information was considered (cited from IUCLID5 data file, section 4):

Parameter

Value used for CSR

Molecular weight

141.11 g/mol

Melting point

Decomposition at 245 °C

Boiling point

Decomposition at 245 °C

Density

1.42 g/cm3(at 15 °C)

Vapour pressure

0.001 Pa (at 20 °C)

Partition coefficient n-octanol/water (log POW)

0.480 (at 25 °C)

Water solubility

> 10 g/L (at 25 °C) / 49.9 % w/w

pH

ca. 12

pKa

8.57 (at 25 °C)

Particle size

The substance is manufactured and marketed as aqueous solution

 

Absorption:

Based on above data the substance may be absorbed through the skin in relevant amounts (molecular weight < 500 g/Mol, -1 < log POW< 4, see EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRETORATE-GENERAL: Guidance Document on Dermal Absorpiton Sanco/222/2000 rev. 7 19 March 2004). This assumption is supported by the criteria mentioned in Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance, November 2012, Table R.7.12 -3): The physical state as solution and the skin corrosive properties will increase the skin absorption.

For exposure assessments a default value of 100 % of absorption after dermal exposure may be appropriate.

The uptake after direct inhalation of the substance may be of low relevance due to the fact that the substance is manufactured and marketed as an aqueous solution only. Uptake by inhalation after evaporation is unlikely, the substance as such is a solid at room temperature and has a very low vapour pressure.

The absorption after oral ingestion cannot be calculated due to lack of data; Taking into account information from acute toxicity and repeated dose toxicity studies where systemic toxicity occured after oral exposition, relevant ammounts are absorbed by this route.

By default an absorption of 100 % may be appropriate, until specific data will be available, although such a high absorption is rather unlikely.

 

Distribution:

The substance is highly hydrophilic as a salt at high pH values. In physiological media like body fluids the conjugated acid Benzotriazole will be formed, which is neither highly lipophilic nor hydrophilic the fact of which makes an estimation on which body compartment would be preferred for distribution in the human body practically impossible such that a more detailed description is futile.

Due to the log Pow of 1.44 only a low potential for bioaccumulation is expected.

Metabolism and Excretion:

Taking into account the structural elements of the formula it follows that typical functional groups for phase II metabolic reactions are not present (like hydroxyl- or amine-groups).

The study by Hoffmann which investigated the conjugated acid Benzotriazole indicates a low metabolic conversion of 1H-Benzotriazole (<2 % are metabolized within 1 hour in liver extract). A Hydroxylation at the benzole moiety is seen which is a phase I metabolic reaction.

Based on this functionalisation phase II reactions can occur. The Hydroxy group can be the substrate for sulfotransferases, acetyltransferases and for glucuronidation.

All of these reactions will increase the water solubility of the substance and improve urinary excretion, which may be the most relevant way of excretion for this substance.

But even when the water solubility stays low, a renal excretion of the unchanged molecule is possible.

Another relevant pathway for excretion may be by faeces, especially for the fraction, which has not been absorbed in the gastrointestinal tract after oral uptake.

Excretion by exhalation does not seem to be relevant.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
Based on the physicochemical data, available toxicological information and the supporting study by Hoffmann the toxicokinetic properties of Sodium Benzotriazolate are assessed.
Executive summary:

Absorption: for the dermal and oral route, an absorption of 100% is assumed,

For the inhalative route no relevant absorption is estimated and 10% is assumed.

Distribution: based on available information it is not possible to make a detailed assessment.

Due to the log Pow of 1.44 only a low potential for bioaccumulation is expected.

Metabolism and Excretion: metabolism rate is rather low (supporting study) and no Phase II reactions may occur.

Renal and faecal excretion are the prominent excretion routes.

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