Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Assessment of the toxicokinetic behaviour of the substance to the extent that could be derived from the relevant available information
Type of information:
other: Assessment (literary search)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report Date:
2020

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Doses / concentrationsopen allclose all
Dose / conc.:
1 457 other: mg/kg
Remarks:
EPA Guideline Series 81-1
LD50 (male), 95 % confidence limits: 1271 to 1670 mg/kg)
Dose / conc.:
1 033 other: mg/kg
Remarks:
EPA Guideline Series 81-1
LD50 (female), 95% confidence limits: 881 to 1212 mg/kg)
Dose / conc.:
200 mg/kg bw/day
Remarks:
BIO Acute dermal
Dose / conc.:
1 000 mg/kg bw/day
Remarks:
BIO acute dermal
Dose / conc.:
2 000 mg/kg bw/day
Remarks:
BIO acute dermal
Dose / conc.:
3.48 mg/L air
Remarks:
BIO acute inhalation
Dose / conc.:
100 mg/kg bw/day
Remarks:
BIO DRFE 14 oral
Dose / conc.:
300 mg/kg bw/day
Remarks:
BIO RDFE 14 oral
Dose / conc.:
600 mg/kg bw/day
Remarks:
BIO RDFE 14 oral
Dose / conc.:
900 mg/kg bw/day
Remarks:
BIO RDFE 14 oral
Dose / conc.:
50 mg/kg bw/day
Remarks:
BIO 28 oral
Dose / conc.:
150 mg/kg bw/day
Remarks:
BIO 28 oral
Dose / conc.:
300 mg/kg bw/day
Remarks:
BIO 28 oral
Dose / conc.:
62.5 mg/kg bw/day
Remarks:
BIO RPD screening
Dose / conc.:
125 mg/kg bw/day
Remarks:
BIO RPD screening
Dose / conc.:
250 mg/kg bw/day
Remarks:
BIO RPD screening
Details on dosing and sampling:
TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, blood, plasma, serum or other tissues, cage washes, bile
- Time and frequency of sampling:
- Other:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, tissues, cage washes, bile
- Time and frequency of sampling:
- From how many animals: (samples pooled or not)
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC)
- Limits of detection and quantification:
- Other:
TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable):

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Absorption from gastrointestinal tract for 1 mg dose (%) = 100 (Lipinski's Rule-of-five score (bioavailability) = 0), EQUATION FROM LITERATURE
Type:
absorption
Results:
Absorption from gastrointestinal tract for 1000 mg dose (%) = 95 (Lipinski's Rule-of-five score (bioavailability) = 0), EQUATION FROM LITERATURE
Type:
absorption
Results:
Dermal absorption (mg/cm2/event) 0.0179 (EPI DERMWIN)
Type:
distribution
Results:
Log brain/blood partition coefficient 0.4955 (EQUATION FROM LITERATURE)

Applicant's summary and conclusion

Executive summary:

The chemical evaluated ( 3-(isodecyloxy)propylammonium acetate )belongs to cationic surfactants. The literature sources mentioned that cationic surfactants are substances of low acute toxicity and exhibit strongly irritation effect exhibit on the mucous membrane of the gastrointestinal tract (SFT 1991,SCCSand others).

This is in agreement with findings of above mentioned studies.

 

Isomaa and Ekman (1975) stated thatadministrations of quaternary ammonium surfactant to pregnant mice in an ip dose corresponding to 10 or 33% of the LD50 increased the incidence of malformations, principally cleft palate and minor skeletal defects in the skull and sternum. Cationic surfactants are known to affect the permeability of cells and tissues and it is possible that the embryotoxic and teratogenic effects are due to a disturbance of the functional integrity of the placenta.

This is not the case of our chemical.

 

Isomaa (1975)studied the absorption, distribution and excretion of orally administered [14C]CTAB, (the same quaternary ammonium surfactant mentioned above), in female rats. About 80% of the dose of radioactivity was found in the gastro-intestinal tract 8 hr after administration, only small amounts were found in the blood plasma and about 2% of the administered radioactivity was excreted in the bile during the first 12 hr after treatment. The low levels of radioactivity in the serum and bile, together with the large amounts of radioactivity found in the gastro-intestinal tract, indicated poor intestinal absorption of CTAB. Only small amounts of radioactivity were found in the liver, kidneys, spleen, heart, lungs and skeletal muscle, and the tissue radioactivity declined rapidly. Within 3 days of ingestion, 92% of the administered radioactivity had been excreted in the faeces and 1% in the urine.

These findings are in large extent in agreement with the resulst of studies mentioned in part 2 of assessment report.

 

QSAR models estimated for the chemical evaluated the poor dermal absorption, very good absorption from gastrointestinal tract and for bioavailability the score 0 (Lipinskiscores of 0 or 1 means that the substance may be bioavailable).

With this last statement we could identify.