Sodium hydrogen N-(1-oxotetradecyl)-L-glutamate

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion - in vivo:

A study was conducted to determine the in vivo skin irritation / corrosion potential of the read-across substance L-glutamic acid, N-coco acyl derivs., monosodium salts according to OECD Guideline 404, in compliance with GLP. New-Zealand White rabbits were exposed to 0.5 mL of undiluted test substance for 4 h.The experiment consisted of a semiocclusive coverage on a clipped skin free of fur. Following application, animals were observed after 1, 24, 48 and 72 h. The mean scores for erythema and oedema were between 0.7 and 1.0 and all effects were reversible within 7 d. Under the study conditions, the substance was not irritating to rabbit skin (Safepharm Laboratories Limited, 1989). A supporting study was conducted to determine the in vivo skin irritation / corrosion potential of the read-across substance Reaction mass of L-Glutamic acid, N-(1-oxooctyl)-, sodium salt and N-L-glutamyl-L-glutamic acid, N'-(1-oxooctyl)-, sodium salt in humans according to Method: T11C: "Skin irriation through patch test", in compliance with GLP and GCP. The method consists in an occlusive application of the test substance by means of Finn Chambers (aluminium cells of 20 microlitres volume) on 20 selected subjects’ back or forearm. The irritating activity/power (%) was clinically evaluated after 30 minutes (T1) following application (immediate irritative power) and 48 hours later (T2) (irritative power); by observing the erythema induced by the test substance. Test substances were then ranked on a statement scale ranging from “non irritating” to “strongly irritating” on the basis of the severity of the irritating reactions observed as well as their frequency in the different subjects. A second check was made 24 hours after the removal of the plaster strip. The irritating power of the test substance was 0% and 24 hours after the test substance removal; no cases of delayed irritation/allergic were either observed or reported. None of the subjects reported itching phenomena. Under the study conditions, the substance was not considered to be irritating to human skin (Sirigu, 2000). Another in vitro test was performed on the potassium salt of the substamce. Disks of EPISKIN (three units / chemical) were treated with Potassium hydrogen N-(1-oxotetradecyl)-L-glutamate / Acylglutamate MK-11-T and incubated for 15 minutes at room temperature. Exposure of test material was terminated by rinsing with PBS. Epidermis units were then incubated at 37°C for 42 hours in an incubatorwith 5% CO2. The viability of each disk was assessed by incubating the tissues for 3 hours with MTT solution at 37°C in 5% CO2 protected from light. The formazan extract in acidified isopropanol was then spectrophotometrically evaluated for optical density (OD) and quantified.
SDS 5% and PBS treated epidermis were used as positive and negative controls
respectively. For each treated tissue, optical density (OD) was calculated and the tissue viability was expressed as a % relative to negative control. If the mean relative viability after 15 minutes exposure and 42 hours post incubation is less or equal (≤) to 50% of the negative control, the test substance is considered to be irritant to skin.
As the test item has an intrinsic colour, one additional chemical-treated tissue was
used for the non specific OD evaluation. Optical density (measured at 540 nm) of this tissue was determined as 0.034, and this value was subtracted from the measured OD value for the test item. Non Specific Colour % was calculated as 4.5%, therefore additional data calculation was not necessary.
Following exposure with Potassium hydrogen N-(1-oxotetradecyl)-L-glutamate /
Acylglutamate MK-11-T, the mean treated skin value was 88% and therefore non
irritant. All validity criteria were within acceptable limits and therefore the study can be considered as valid. In this in vitro skin irritation test in the EPISKIN model with Potassium hydrogen N-(1-oxotetradecyl)-L-glutamate / Acylglutamate MK-11-T the results indicated that the test item is Non Irritant (NI) [UN GHS: No Category]. As the target substance is the sodium salt and sodium salt are usually less toxic that potassium, the test is valid. The reconstructed human epidermis model EPISKIN-SM is designed to predict and classify the corrosive potential of chemicals, by measuring its cytotoxic effect, as reflected in the MTT assay, on the EPISKIN reconstituted human epidermis. This method is approved by international regulatory agencies as a replacement for the identification of irritants / corrosives in the in vivo Rabbit skin assay (OECD 404) and is specifically approved as a replacement for the in vivo skin corrosivity test within OECD 431.
Disks of EPISKIN (three units / chemical) were treated with test item Potassium
hydrogen N-(1-oxotetradecyl)-L-glutamate / Acylglutamate MK-11-T and incubated
for 4 hours at room temperature. Exposure of test material was terminated by rinsing with PBS 1x solution (0.9 %). The viability of each disk was assessed by incubating the tissues for 4 hours with MTT solution. The formazan precipitated was then extracted using acidified isopropanol and quantified spectrophotometrically. NaCl (9 g/L saline) and glacial acetic acid treated epidermis were used as negative and positive controls. An additional disk was used to provide an estimate of colour contribution from the test item. For each treated tissue viability was expressed as a % relative to negative control. If the mean relative viability after 4 hours of exposure is below 35% of the negative control, the test substance is considered to be corrosive to skin.
Following exposure with Potassium hydrogen N-(1-oxotetradecyl)-L-glutamate /
Acylglutamate MK-11-T, the mean cell viability (after adjustment for colour) was
98% compared to the negative control and therefore non-corrosive. All validity criteria were within acceptable limits and therefore the study can be considered as valid.
In this in vitro EPISKIN model test with Potassium hydrogen
N-(1-oxotetradecyl)-L-glutamate / Acylglutamate MK-11-T, the results indicate
that the test item is not a skin corrosive. As the target substance is the sodium salt and sodium salt are usually less toxic that potassium, the test is valid.

Eye irritation - in vivo:

A study was conducted to determine the in vivo eye irritation potential of the read-across substance L-glutamic acid, N-coco acyl derivs., monosodium salts according to OECD Guideline 405, in compliance with GLP. Eyes of New-Zealand White rabbits were exposed to 0.1 mL of the undiluted test substance. The other eye served as control. Following application, animals were observed after 1, 24, 48 and 72 h. The mean scores for cornea, conjunctiva, iris effects and chemosis were determined to be 1.8, 2.9, 1.0 and 2.4. All effects were reversible within 14 d. Under the study conditions, the substance was considered to be irritating to rabbit eye (Safepharm Laboratories Limited, 1989). BCOP test was also performed on the substance.The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (Ethanol) was 50 and was within two standard deviations of the current historical positive control mean. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. Sodium hydrogen N-(1-oxotetradecyl)-L-glutamate induced ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 4.3 after 10 minutes of treatment.Since Sodium hydrogen N-(1-oxotetradecyl)-L-glutamate induced an IVIS > 3 ≤ 55, no prediction on the classification can be made. Also EpiOcular test was performed on the substance. Sodium hydrogen N-(1-oxotetradecyl)-L-glutamate was checked for colour interference in aqueous conditions and possible direct MTT reduction by adding the test item to MTT medium. The test item did not cause direct reduction of MTT but the compound showed colour interference. Therefore in addition to the normal procedure, two additional tissues were treated with the test item. Instead of MTT solution these tissues were incubated with assay medium. The non-specific colour of the test item was 0.72% of the negative control tissues. The mean Optical Density (OD) of the treated tissues without MTT assay was subtracted from the ODs of the test item treated viable tissues with MTT assay. Eye hazard potential is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 30 ± 2 minutes treatment with the test item compared to the negative control tissues was 16%. Since the mean relative tissue viability for the test item was below 60% after 30 ± 2 minutes treatment the test item is considered to be potentially irritant or corrosive to the eye. Finally, it is concluded that this test is valid and that Sodium hydrogen N-(1-oxotetradecyl)-L-glutamate is potentially irritant in the EpiOcular™ test under the experimental conditions described in this report.

Justification for classification or non-classification

Based on in vivo/in vitro skin and eye irritation studies reported  the substance warrants classification as Eye Irrit. 2: H319 (Causes serious eye irritation) according to EU CLP (1272/2008) criteria.