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Description of key information

The toxicokinetics of the substance CAS 1195028-55-7/ EC 939-992-3 has been assessed based on the physicochemical properties and available toxicological data following the ECHA Guidance R.7c from November 2012 (version 1.1).

As a result, it has been found that the substance is expected to be absorbed from the gastro-intestinal tract. The respiratory deposition is assessed to be low and the dermal absorption could occur on certain extent.

Distribution in the body is expected to take place, mainly based upon the water solubility and the clinical observations and target organs seen in the toxicity studies.  

Limited data were available for estimation of metabolism (increased kidney weights were observed in rats). Based on the chemical structure it is known that the present double bonds -C=C- or –N=N- might react with strong acids (pH << 4) to give new structures. From the biodegradability testing it was concluded that the test item was not readily biodegradable but showed biodegradation and is considered as inherently biodegradable. Bioaccumulation is not expected, based on the log Kow and the calculated BCF values.

Based on the physicochemical properties of the substance only one route of excretion (urine) was assessed as possible.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
50

Additional information

The assessment below is based on theECHA Guidance on information requirements and chemical safety assessment (Chapter R.7c: Endpoint specific guidance, November 2012 Version 1.1), for which physicochemical data may be used for a qualitative Toxicokinetics assessment. All data needed are part of the REACH registration dossier of the substance.

 

Absorptionof CAS 1195028 -55 -7/ EC 939 -992 -31 was assessed based on physicochemical and available toxicological data. The substance is a solid with a molecular weight of ca 1155 and a water solubility of 149 g/L. The octanol-water partition coefficient (log Kow) is -4.47. These values of log Kowand molecular mass of the substance don’t suggest an absorption into the body.

 (a)  Oral/GI absorption:

 

The compound is ionisable and highly soluble in water. Its high molecular weight and because of the log Kowvalue of -4.47 (not in the range -1 to 4), the compound should not be easily involved in a micellular solubilisation and this fact doesn’t favor the oral absorption.

No signs of toxicity appeared in acute oral toxicity studies that support the substance is not easily absorbed by oral route. However there are certain signs of toxicity in repeated dose toxicity studies that indicate the compound is absorbed from the gastro-intestinal tract in a certain level.

The considered value for Chemical Safety Assessment of oral absorption 50% is the value taken from the ECHA Guidance.

  (b)  Respiratory absorption:

 

N-octanol/water partition coefficient and molecular weight of the substance doesn’t favor absorption. The substance is a solid and not volatile and it is not expected a high exposure by inhalation route. However if some of the substance is inhaled, it can be expected to be absorbed, based on the high solubility. In practice, absorption is assumed to be low based on the physical properties and the physical status (solid) with a particle size >100 μm.

The considered value for Chemical Safety Assessment of inhalation absorption 50% is considered to better reflect the substance behaviour than the value of the ECHA Guidance proposed to be 100%.

(c)  Dermal absorption:

 

This route of exposure is the most probable one.

Based upon the fact that the substance is a solid with a high molecular weight, log Kowof -4.47 and not showing skin irritation, sensitization and/or acute dermal toxicity, it might be expected that the substance is not absorbed by the skin. The dermal absorption degree is increased when the substance is in a water solution form.

Having all this factors into account the dermal absorption is considered to be low to moderate.

 

The value considered for Chemical Safety Assessment of dermal absorption is the value proposed in ECHA Guidance for dermal absorption, 50%.

For the assessment of distribution, metabolism and excretion, physicochemical and available toxicological properties are also taken into account according to ECHA guidance Chapter R.7c. 

 

Distribution:

Based upon the molecular weight ca.1155 g/mol, high water solubility of 149 g/L and logKowof -4.47, distribution in the body is expected to take place slowly but in certain extent. This is further confirmed by effects in clear target organs (kidneys) and observations from the toxicity studies.

 

Metabolism and accumulation potential: 


Metabolism cannot be deduced from the data available, except for the increase in kidney weights in male and female rats dosed at 750 mg/kg bw and 300 mg/kg bw day, and haemotogical changes in the repeated dose toxicity study.

Regarding bioaccumulation potential, the available data from biodegradation studies show that although the substance can’t be classified as “readily biodegradable” a 48% of degradation is observed after 21 days and the substance will biodegrade along time. The BCF calculated value is 3.162 L/kg ww, which is well below the threshold value of 2000 L/kg for a PBT substance as indicated by the REACH Guidance on PBT assessment. Therefore, the substance is not expected to bio-accumulate in the body.

 

Excretion:


Based on the high molecular weight and pKavalue the urinary excretion of the parent compound would not be expected. However the high water solubility, could favor this route of elimination. Excretion via the saliva and sweat is considered less possible based on the low log Kowvalue (-4.45). Also exfoliation should not be applicable. Excretion in the breast milk is not considered to be the main route. Therefore only one route of excretion is available to reduce the substance in the body.

However it should be considered that the substance could be degraded at gastro-intestinaI pH 1-4 and won’t be eliminated as such.