N-(2-carboxyethyl)-N-octyl-β-alanine

Endpoint summary

Description of key information

A 28 day oral toxicity study performed according to OECD Guideline 407 and under GLP with Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6 is available, with reliability rating 1. Based on the absence of functional or morphological disturbances supporting the changes noted in the study, a NOAEL of > 1000 mg/kg was established.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The study is performed according to OECD 407 guideline and under GLP and has reliability rating 1. It is sufficient to cover the information requirements in Annex VIII.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A 28-day oral toxicity study according to OECD 407 has been performed on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6. The dose levels tested were 1000 mg/kg/day, 300 mg/kd/day and 50 mg/kg/day. This study was performed according to the current OECD 407 and EU method B7 protocols, with full GLP compliance and a well-defined test substance. No adverse effects were found in the study. The histopathology showed that the statistically higher thymus weight seen in females at 1000 mg/kg were minor, non-adverse, treatment-related lymphocytolysis. Since lymphocytolysis is a common background finding and based on the incidence, degree and lack of clear dose-relation seen in this study, this finding was not considered to be an adverse effect of the test item.

The parental toxicity effects reported in as 2-generation reproduction study on rats (parental dosing for 16 weeks) are consistent with the effects reported in the other repeat dose studies on these primary amine alaninates. The liver changes are indicative of metabolic processes and the results are also consistent with alklyamines suggesting similar toxicological mechanisms

The minimal lymphoid hyperplasia in the mesenteric lymph nodes of the males and the remaining microscopic findings recorded were within the normal range of background pathology encountered in Wistar(Han) rats of this age and strain. No adverse toxicity findings were observed up to the highest dose level tested, and a NOAEL value could therefore not be defined. The highest dose tested is therefore reported as NOAEL value for these this endpoint, since the use of ">" is not possible in the IUCLID filed specified for effect level.

 

The data from the 28 day oral toxicity study is therefore used to determine the DNEL values for oral, inhalation and dermal exposure following the ECHA guidance document for deriving DNEL values. As appropriate DNEL values can be calculated using the oral dosing study data, and due to the low vapour pressure of the substance, it is not justified on animal welfare grounds to perform repeat dose dermal or inhalation toxicity studies.

Work on analogue substances reviewed include further repeat dose oral testing (including dosing for reproduction tests) and these confirm low chronic toxicity with effects generally linked to liver function and some effects on kidneys. These have been considered in some cases to be adaptive and indicate metabolic processes.

This EPA study is considered valid in terms of grouping of substances. Examination of data on various primary alkylamines show little difference in repeat toxicity effects, including reproduction. Read-across is considered valid as the results are consistent with the findings in the more recent 28 days study (key study); this study show more adverse effects and is therefore considered a suitable surrogate for the reporting of reproductive effects.

The similarity in findings with the work on primary amines further justifies read-across to these potential metabolites. This is reviewed in the assessment report attached in Section 13.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

The only available 28-day oral toxicity study on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, is performed according to OECD 407 guideline under GLP conditions and has reliability rating 1. No adverse effects were seen in any of the selected doses in the study, and a NOAEL value could therefore not be defined. The highest dose tested is therefore reported as NOAEL value for this endpoint and used for DNEL derivation, since the use of ">" is not possible in the IUCLID filed specified for effect level below.  

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

There is no repeat dose inhalation study Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, however the substance is a paste with a low vapour pressure of < 1.5 mPa at 20°C. Significant exposure to vapours would not be expected at ambient temperatures so it is considered to not be scientifically valid to conduct a repeat dose inhalation study.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:

There is no repeat dose inhalation study Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, however the substance is a paste with a low vapour pressure of < 1.5 mPa at 20°C. Significant exposure to vapours would not be expected at ambient temperatures so it is considered to not be scientifically valid to conduct a repeat dose inhalation study.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

There is no repeat dose dermal study Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, but a 28 day oral toxicity study according to OECD 407 is available. Based on the physicochemical properties of the substance, it is considered very unlikely that dermal absorption would exceed oral absorption, so it would be expected than the oral NOAEL would be lower than a corresponding value from a dermal study. Results from the two acute toxicity tests available on the substance show no differences in toxicological profile, LD50 is > 2000 mg/kg bw for both exposure routes. Data from the repeat dose oral study can be used in the setting of DNELs in accordance with the REACH guidelines. As appropriate DNEL values can be calculated using the oral dosing study data, it is not justified on animal welfare grounds to perform a repeat dose dermal toxicity study.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:

There is no repeat dose dermal study Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, but all three acute skin irritation / corrosion studies and the one acute dermal toxicity study in combination with the 28 day oral toxicity study indicates low toxicity of the substance. This does not justify the requirement for an additional dermal animal study to establish a local NOAEL for dermal exposure.

Justification for classification or non-classification

The EU CLP (GHS) criteria for classification for Specific Target Organ Toxicity (STOT) are based on data from a 90 day study, for Category 2 the range for such effects is 10-<100 mg/kg/day. Where the data are from a 28 day study these levels are multiplied by three. However there were no indications of any specific systemic toxic effects such as serious organ damage in any of the dose groups of Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6. Based on the lack of findings from the available 28 day oral toxicity study, there is no evidence of relevant specific target organ toxicity in the rats dosed at up to the highest dose level of 1000 mg/kg/day. Therefore it does not have to be classified and has no obligatory labelling requirement according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011), nor the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.