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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across study hence maximum reliability rating of 2 assigned according to ECHA guidance, although the study is well documented study, meets generally accepted scientific principles, acceptable for assessment.
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Lauramide diethanolamine absorption, metabolism, and disposition in rats and mice after oral, intravenous, and dermal administration
Author:
Mathews JM, deCosta K and Thomas BF
Year:
1996
Bibliographic source:
Drug metabolism and disposition 24(7): 702-710

Materials and methods

Objective of study:
absorption
excretion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
This study was conducted as a 3 wk repeated dose study at a single dose level (25 mg/kg bw) in rats through dermal route.

GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N-bis(2-hydroxyethyl)dodecanamide
EC Number:
204-393-1
EC Name:
N,N-bis(2-hydroxyethyl)dodecanamide
Cas Number:
120-40-1
Molecular formula:
C16H33NO3
IUPAC Name:
N,N-bis(2-hydroxyethyl)dodecanamide
Details on test material:
- Name of test material (as cited in study report): Lauramide diethanolamine (LDEA)
- Radiochemical purity (if radiolabelling): 96 to 97 %
- Specific activity (if radiolabelling): 841 µCi/mmol
- Locations of the label (if radiolabelling): On the DEA moiety
- Other: Identity confirmed by: Mass spectrometry and proton NMR
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc. (Raleigh, NC)
- Age at study initiation: 81 to 87 d
- Housing: Individual glass metabolism chambers, which allowed separate collection of carbon dioxide, urine, and feces.
- Individual metabolism cages: Yes
- Diet: Purina Rodent Chow (no. 5002), ad libitum
- Water: Ad libitum

Administration / exposure

Route of administration:
dermal
Vehicle:
not specified
Details on exposure:
DOSE APPLICATION: [14C] LDEA was administered on Days 3, 10, and 17 and non-radiolabeled LDEA was administered on all other days.


USE OF RESTRAINERS FOR PREVENTING INGESTION: Yes, some of the animals had protective appliances, which prevented both the animal’s access to the dose site during grooming and the escape of dander containing LDEA into the metabolism cages.
DOSE FORMULATION: 16 to 18 µCi radiolabel per dose
Duration and frequency of treatment / exposure:
Duration of treatment: 3 wk
Frequency of treatment: 5 d/wk


Doses / concentrations
Remarks:
Doses / Concentrations:
25 mg/kg bw

No. of animals per sex per dose / concentration:
Five
Control animals:
no
Positive control reference chemical:
No data

Details on study design:
No information




Details on dosing and sampling:
PHARMACOKINETIC STUDY (Excretion)
- Tissues and body fluids sampled: Urine and faeces
- Time and frequency of sampling: 6, 24, 48 and 72 h on Day 3, 10 and 17


METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine, faeces, tissues, cage washes, bile



Statistics:
Not reported

Results and discussion

Preliminary studies:
Not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:
- 70-85% dermal absorption of lauramide diethanolamine was observed.


Details on distribution in tissues:
Not examined


Transfer into organs
Transfer type:
other: not determined
Details on excretion:
- The flux of LDEA doubled from the first week to the last and only statistically significant differences were observed between the 48 and 72 h collection periods starting on Day 3 and 17 (For details see Table 1 in the attached document).

Toxicokinetic parameters
Toxicokinetic parameters:
other: Not determined

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Only radioactivity of metabolised LDEA was detected in the cage urine.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
Under the test conditions, 70-85 % of the test substance was dermally absorbed and metabolised with only metabolised test substance present in the urine.
Executive summary:

A dermal toxicokinetic study was conducted to evaluate the absorption and excretion of the radiolabelled (14C) lauramide diethanolamine (LDEA) in the F344 rats.

Five male Fischer rats were exposed to 25 mg/kg of the test substance through dermal route 5 d/wk for 3 wk. Radiolabelled test substance was administered on Day 3, 10, and 17 and non-radiolabeled test substance was administered on all other days.

Between 70-85 % dermal absorption of the test substance was observed. The flux of the test substance doubled from the first week to the last and only statistically significant differences were observed between the 48 and 72 h collection periods starting on Day 3 and 17. Analysis of cage urine revealed only presence of metabolised test substance.

 

Hence, under the test conditions, 70-85% of the test substance (LDEA) was dermally absorbed. Only metabolised LDEA was present in urine.