Amidation products of C16-18 (even numbered), C18 unsaturated fatty acids esters with 1,1'-iminodipropan-2-ol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Written assessment

Type of information:

other: Written assessment

Adequacy of study:

other information

Study period:

December 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Written assessment

Justification for type of information:

At the current level of registration, a written assessment is suitable. Please see attached justification below.

Data source

Reference

Reference Type:

other: Written assessment

Title:

Unnamed

Year:

2018

Materials and methods

Objective of study:

other: Written assessment of ADME

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Written assessment based on available study data.

Test material

Test material information

Constituent 1

Reference substance name:

Amidation products of C16-18 (even numbered), C18 unsaturated fatty acids esters with 1,1'-iminodipropan-2-ol

EC Number:

701-003-6

Cas Number:

1454803-04-3

Molecular formula:

C20H39NO3 to C26H51NO3

IUPAC Name:

Amidation products of C16-18 (even numbered), C18 unsaturated fatty acids esters with 1,1'-iminodipropan-2-ol

Test material form:

liquid

Details on test material:

Identification: MLA-3202
Appearance: Clear amber-red liquid
Purity/Composition: UVCB
Test item storage: At room temperature
Stable under storage conditions until 17 February 2019 (expiry date)
Purity/composition correction factor: No correction factor required
Chemical name (IUPAC), synonym or trade name: Amides, tallow, N,N-bis(2-hydroxypropyl)
CAS Number: 1454803-04-3
Test item handling No specific handling conditions required

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

See above justification

Details on distribution in tissues:

See above justificationSee above justification

Details on excretion:

See above justification

Metabolite characterisation studies

Details on metabolites:

See above justification

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

See above justification

Applicant's summary and conclusion

Conclusions:

In conclusion, there is no evidence that the substance is significantly absorbed via the dermal route or the inhalation route, but for worst case risk assessment, 100% absorption is proposed. The results of an oral repeated dose toxicity study indicate that the substance may be absorbed orally. This is further confirmed by the extensive metabolic studies conducted on the closely related substance lauramide DEA. Lauramide DEA, following absorption in rodents, is metabolized to the half-acid amides of succinic and of adipic acid. These metabolites would arise from the ω-hydroxylation and eventual β-oxidation to give the chain-shortened products. The metabolism studies conducted by Mathews et al. (1996) on the analogue demonstrate that the amide moiety is not hydrolysed; hence the lack of potential for amine formation. Since ω-hydroxylation and β- oxidation are the only noted means of metabolism (these are common metabolic pathways for dietary fatty acids and triglycerides), there is no possibility that reactive, or potentially mutagenic intermediates, can be formed. The metabolic data on the close structural analogue lauramide DEA corroborates the conclusion that the substance is not considered to be bioaccumulative, and would be metabolised for elimination via urine.

Executive summary:

In conclusion, there is no evidence that the substance is significantly absorbed via the dermal route or the inhalation route, but for worst case risk assessment, 100% absorption is proposed. The results of an oral repeated dose toxicity study indicate that the substance may be absorbed orally. This is further confirmed by the extensive metabolic studies conducted on the closely related substance lauramide DEA. Lauramide DEA, following absorption in rodents, is metabolized to the half-acid amides of succinic and of adipic acid. These metabolites would arise from the ω-hydroxylation and eventual β-oxidation to give the chain-shortened products. The metabolism studies conducted by Mathewset al. (1996) on the analogue demonstrate that the amide moiety is not hydrolysed; hence the lack of potential for amine formation. Since ω-hydroxylation and β- oxidation are the only noted means of metabolism (these are common metabolic pathways for dietary fatty acids and triglycerides), there is no possibility that reactive, or potentially mutagenic intermediates, can be formed. The metabolic data on the close structural analogue lauramide DEA corroborates the conclusion that the substance is not considered to be bioaccumulative, and would be metabolised for elimination via urine.