12-aminododecanoic acid

Endpoint summary

Description of key information

A toxicokinetic study has not been performed but a toxicokinetic assessment has been prepared 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

25

Absorption rate - inhalation (%):

100

Additional information

Introduction

Physico-chemical properties and the results of in vitro studies and acute and repeat dose toxicity studies with animals for 12-aminododecanoic acid (CAS 693-57-2) have been used to determine a toxicokinetic profile.

Physicochemical properties

The substance 12-aminododecanoic acid is a white powder and has the molecular formula C12O2NH27 with a molecular weight of 217.1 g/mol. It is relatively soluble, the maximum solubility being 137 mg/L at 25°C, with a log Pow value of -0.607 at 25°C (Walker and Mullee, 2007). Aminododecanoic acid contains a carboxylic acid and an amino group and is zwitterionic in nature, with a neutral pH, and a pKa and pKb of 4.8 and 10.7 respectively.

Absorption

Oral absorption

Oral absorption was experimentally evident from pathology manifesting in the OECD 422 study conducted by Dhinsa and Petrie (2007). Nothing could be inferred about the extent of oral absorption however.

Estimation of the extent of mammalian oral absorption is made on basis of similarity to fatty acids which are readily absorbed through incorporation into micelles and absorption via the lymphatic system, and the physical chemical properties of the substance which allow it to be taken up through the mass uptake of water and/or aqueous pores across membranes. The physical chemical properties are comparable with those delineated by ECHA (2012) for such absorption processes across the gastrointestinal tract (sufficiently water soluble given anticipated exposure: 137 mg/L; small MW of up to around 200 g/mol, a Pow between -1 and <4).

A value of 100% is assumed oral absorption for all mammalian species, where present at levels comparable to those that might be experienced under occupational exposure scenarios.

Dermal absorption

Estimation of mammalian dermal absorption is made in accordance with principles adopted within the EFSA guidance on estimating dermal absorption of pesticide active substances (EFSA, 2012). On this basis, dermal absorption is estimated at 25% for undiluted material. This is considered an appropriate estimate because values of ca 25% were obtained in vivo in rats for substances with a MW of ca. 271 -288. These were very conservative estimates in themselves given one was based on a dilution and high skin residues were included in the other. In addition no correction for human skin was made. Therefore, taking into account the slightly smaller molecular weight for 12-aminododecanoic acid of 217.1 g/mol, 25% is considered a reasonable estimation of the human dermal penetration.

Inhalation

In the absence of any other data, absorption of material reaching the alveoli is estimated at 100%.

Distribution

Distribution is estimated to be wide throughout the body. The OECD 422 toxicity study (Dhinsa and Petrie, 2007) shows only relevant toxicology in red blood cells and the kidney. This may suggest some preferential partitioning into RBC membranes. The kidney is an organ of excretion and total exposure of kidneys to the test material might reasonably be expected to be greater than other organs.

Metabolism

Not Known. The material was readily biodegradable in aerobic sewage sludge (Kitano, 1985). At low doses metabolism by gut flora may perform the majority of metabolism prior to absorption.

Elimination

Not known. Given the molecule is of low molecular weight (<300 g/mol, above which biliary excretion tends to predominate) and appears readily biodegradable (achieving smaller fragments), elimination is estimated to be via the kidney given the pathology observed in the OECD 422 study (Dhinsa and Petrie, 2007). The pathology consisted of a) groups of basophilic tubules; b) tubular dilatation; c) hypertrophy collecting duct epithelium; d) hyperplasia pelvic/papillary epithelium. The same lesions (and others) were observed also in animals of both sexes at 1000 mg/kg at termination, and most of them (i.e. a), c) and d)) were still observable in recovery animals, thus suggesting that the damage was permanent. In contrast there was no pathology observed in the liver.

It is not know how rapid excretion would be.

Conclusion

The substance 12-aminododecanoic acid is expected to be readily absorbed after ingestion, and absorption is expected to be 100% at typical occupational exposure levels. Dermal absorption is estimated at 25%, whilst inhalation absorption is estimated at 100%. Elimination is expected to be predominantly via the urine.

References

Author (year)	Title Source (where different from company) Company, Report No. GLP or GEP status (where relevant) Published or Unpublished
ECHA (2012)	Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance.  www.echa.europa.eu Not GLP Published
Walker, J. A. and Mullee, D. M. (2007)	12-Aminododecanoic acid: Determination of General Physicochemical Properties. Safepharm Laboratories Limited, Derby, UK Ube Industries Ltd, Report number: 1456/0091 GLP Unpublished
Dhinsa,N. K. and Petrie, A. J. (2007)	12-Aminododecanoic Acid: Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction/Developmental Toxicity Screening Test in the Rat (OECD 422 1996 with Recovery Groups). Safepharm Laboratories Limited, Derby, UK Ube Industries Ltd, Report number: 1456/0083 GLP Unpublished
EFSA (2012)	SCIENTIFIC OPINION: Guidance on Dermal AbsorptionfromEFSA Panel on Plant Protection Products and their Residues (PPR). European Food Safety Authority (EFSA), Parma, Italy. EFSA Journal2012;10(4):2665 Not GLP Published
Kitani, H. (1985)	The Biodegradablity Test of S-153. Chemical Biotesting Center, Chemicals Inspection & Testing Institute, Japan. Ube Industries LTD, Report number: 33314 Not GLP Unpublished