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Description of key information

Short description of key information on bioaccumulation potential result: 
The physico-chemical characteristics of the substance and the absence of significant adverse effects observed in the toxicological studies tend to indicate a limited absorption and a low biodisponibility.
Short description of key information on absorption rate:
Based on physico-chemical properties (MW: 537 ; LogKow <-1.98, high water solubility, poor lipophilicity) and the presence of quaternary ammonium fucntions, the substance is unlikely to be well absorbed by the dermal route.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information

There are no experimental data. A preliminary assessment was made based on the information currently available from the dataset.

Based on the physico-chemical properties, such as molecular weight and logKow, the substance is considered to have a low bioavailability potential by all routes. This is further supported by the low toxicity profile observed in the various studies available.

The substance meets the criteria that allows the use a default value of 10% for dermal absorption for risk assessment purposes (REACH Guidance document, R7.12, EC Guidance document on dermal absorption SANCO 222/2000, 2004).

Discussion on bioaccumulation potential result:

There are currently no experimental toxicokinetics study. The assessment was based on the available dataset.

There was no observation available from the repeated dose toxicity studies providing specific information on potential absorption, metabolisation, distribution and excretion of the substance or metabolites.

 

However, based on the data currently available in the dataset, both from the physico-chenical properties (molecular weight, LogKow, vapour pressure, structure, ionic charge) and toxicological data, the substance is considered to present a low systemic bioavailability by all routes. This is further supported by the low toxicity profile observed.

Discussion on absorption rate:

ABSORPTION

No substance-specific absorption data were available experimentally by any route.

 

1)Skin absorption

Skin permeability estimates:

Input parameters:

MW = 537

log Kow = -1.98

Based on the log Kow a poor lipophilicity is predicted. The MW above 500 is also not in favour of dermal absorption.

 

As estimate of the permeability coefficient (maximum flux across the skin) was conducted using various mathematical models:

> Potts & Guy :           logKp = 0.71logKow – 0.0061MW – 2.72

Kp = 3.96 10-8 cm/h

sources :

- Potts & Guy (1992).Pharm.Res. 9:6693-669

- www.cdc.gov/niosh/topics/skin/skinpermcalc.html

 

> Frasch:    Kp = 4.96 10-10  cm/h

source :www.cdc.gov/niosh/topics/skin/skinpermcalc.html

 

> Modified Robinson  :   Kp = 6.77 10-6    cm/h

source :www.cdc.gov/niosh/topics/skin/skinpermcalc.html

 

> SkinPerm : Kp = 8.83 10-7cm/h

source :http://home.planet.nl/~wtberge/qsarperm.html

 

 

The various mathematical models based on hydrophobicity properties and molecular weight provided Kp estimates ranging from 8.83 10-7(SkinPerm) to 4.96 10-10(Frasch). These figures are all below 10-6 and support a very low percutaneous absorption capacity (Howes et al., 1996. Methods for assessing percutaneous absorption. The report and recommendations of ECVAM Workshop 13. ATLA 24:81-106).

 

Other considerations:

The molecular weight of 537Dalton, and the presence of cationic charged functions are not in favour of a passive diffusion accross biological membranes. (H. Schaefer, T. E. Redelmeier (eds), 1996.In: Skin Barrier – Principles of percutaneous absorption.S. Krager AG (publ.))

Furthermore, the acute dermal toxicity study at level up to 4840 mg/kg (dose expressed for the registered substance, with the residual stabilising water), i.e. 2000 mg/kg for the main TRIQUAT constituent, did not show any signs of systemic toxicity. No clinical signs were noted during the 15-day observation period.

No damages or alteration of the skin integrity are expected as the substance did not induce any signs of skin irritation in vivo.

 

It is generally admitted to consider a default skin absorption factor of 10% for substances with a molecular weight above 500 and a logKow below -1 (REACH guidance document, R.7.12; EC Guidance document on dermal absorption, SANCO/222/2000 rev7, 19 March 2004)