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Description of key information

No studies are available in which the toxicokinetic properties of the test substance are investigated. However, as per REACH guidance document R7. C (ECHA, 2017), information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties. Based on the physicochemical properties, QSAR predictions/modelling as well as the available toxicological data, the test substance is expected to have relatively low to moderate absorption potential via the oral, dermal and inhalation route. It is likely to be metabolised via aliphatic hydroxylation phase-I reaction. Overall, the substance is expected to have low a bioaccumulation potential.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

ABSORPTION:

Oral absorption

Based on physicochemical properties:

According to the REACH guidance document R7.C (May 2014), oral absorption is maximal for substances with a molecular weight (MW) below 500. Water-soluble substances will readily dissolve into the gastrointestinal fluids; however, absorption of hydrophilic substances via passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. Further, absorption by passive diffusion is higher at moderate log Kow vales (between -1 and 4). If signs of systemic toxicity are seen after oral administration (other than those indicative of discomfort or lack of palatability of the test substance), then absorption has occurred.

The substance is a white powder with high water solubility of 221.9 g/L at 20°C and a very low log Kow of -2.4, calculated based on solubility in octanol and water.

Based on the R7.C indicative criteria, the oral uptake of the substance is assessed to be low to moderate, given the average MW not exceeding 500, high water solubility and low log Kow values of the test substance. This is supported by the absence of systemic effects in the 13-week repeat dose study conducted with the read across substance, L-glutamic acid, N-coco-acyl derivs., disodium salts in rats.

Conclusion: Based on the available weight of evidence information, the test substance can be expected to have low to moderate absorption through the oral route. However, in absence of experimental data, a default value of 50% has been considered for the risk assessment.

Dermal absorption

Based on physicochemical properties:

According to the REACH guidance document R7.C (ECHA, 2017), dermal absorption is maximal for substances having MW below 100 together with log Kow values ranging between 2 and 3 and a water solubility in the range of 100-10,000 mg/L. Substances with MW above 500 are considered to be too large to penetrate skin. Further, dermal uptake is likely to be low for substances with log P values <0 or <-1, as they are not likely to be sufficiently lipophilic to cross the stratum corneum. Similarly, substances with water solubility below 1 mg/L are also likely to have low dermal uptake, as the substances must be sufficiently soluble in water to partition from the stratum corneum into the epidermis.

The test substance has an average MW weight of 379 g/mol, high water solubility but log Kow less than 0. This suggests that, the test substance will have a low absorption potential through the skin.

Conclusion: Based on all the available weight of evidence information, the test substance can be expected to have a low absorption potential absorption through the dermal route. However, in absence of experimental data, a default value of 100% has been considered for the risk assessment.

Inhalation absorption

Based on physicochemical properties:

According to the REACH guidance document R7.C (ECHA, 2017), inhalation absorption is maximal for substances with VP >25 KPa, particle size (<100 μm), low water solubility and moderate log Kow values (between -1 and 4). Very hydrophilic substances may be retained within the mucus and not available for absorption.

The test substance, because of its low vapour pressure of 1.2E-04 Pa at 20°C, will not be available as vapours for inhalation under ambient conditions. Therefore, the substance will neither be available for inhalation as vapours nor as aerosols. Further, if at all there is any inhalation exposure, considering the high water solubility of the substance, it is expected to be retained in the mucus and only very little may reach the lower respiratory tract. The absorption fate of the deposited material thereafter is expected to be similar to the oral route/gastrointestinal tract.

Conclusion: Based on all the available weight of evidence information, the test substance can be expected to have low to moderate absorption through the inhalation route. However, in absence of any experimental data, a default value of 100% has been considered for the risk assessment.

METABOLISM:

Based on identified literature:

Available literature on acyl glutamates indicates that these substances do not rapidly dissociate in water (beyond zwitterionic formation) and action by amidases is the most likely first step of metabolism with the formation of fatty acid and glutamic acid (CIR, 2013).

Based on QSAR modelling:

The above evidence is supported by the predicted metabolism for the test substance using rat liver S9 metabolism simulator of the OECD QSAR Toolbox v.3.4. These simulator predicted hydroxylation (oxidation) at the ω positionfor the target substance. For further details, refer to the RA justification.

BIOACCUMULATION:

Based on the MW and physicochemical information (log Kow and water solubility) and metabolism prediction, the bioaccumulation potential of the substance is expected to be low.

EXCRETION:

Based on the average MW and high water solubility, the test substance as such is expected to be excreted via urine.

Reference:

Cosmetic Ingredient Review (CIR), 2013. Safety assessment of amino acid alkyl amides as used in cosmetics. Status: Tentative Report for Panel Review; Release date: September 20, 2013.