Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study report, acceptable with restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Objective of study:

distribution

excretion

Principles of method if other than guideline:

Four male rats were administered with 14C-octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (specific gravity of 8.52 µCi/mg; radiochemical purity >99%) in a single oral-gavage dose of 10 mg/kg bw. The elimination of radioactivity and its retention was determined up to 168 h post administration.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

EC Number:

218-216-0

EC Name:

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Cas Number:

2082-79-3

Molecular formula:

C35H62O3

IUPAC Name:

octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Details on test material:

- Radiochemical purity (if radiolabelling): 99 %
- Specific activity (if radiolabelling): 8.52 µCi/mg

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sisseln animal farm
- Weight at study initiation: ca. 200 g
- Fasting period before study: yes, overnight

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: tetrahydrofurfuryl-alcohol-polyethylene-glycol ether

Details on exposure:

VEHICLE
- Amount of vehicle (if gavage): 0.5 ml

Duration and frequency of treatment / exposure:

single

Doses / concentrations

Remarks:

Doses / Concentrations:
10 mg/kg bw

No. of animals per sex per dose / concentration:

4

Control animals:

no

Positive control reference chemical:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, organs and tissues
- Time and frequency of sampling: Animals were housed in metabolism cages and had free access to food and water. Urine and faeces were collected in 24 hours portion until 168 hours after dosage. Organs and tissues were obtained by dissection of the animals 168 hours after administration.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

The highest residual radioactivity was measured in the heart (0.54 µg/g). Slightly higher levels than blood (0.07 µg/g) showed thyroid, liver, kidney, brown/white fat and aorta (0.21-0.09 µg/g). In all other organs and tissues lower but still detectable levels were found (Table 1).

Details on excretion:

Within 0-48 hours after administration about 73% of the dose was eliminated from the body. Afterwards elimination proceeded slowly and was not fully completed at 168 hours. At that time 96% of the dose was recovered, 35% in the urine and 61% in the faeces (Table 2).

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

Table 1. Distribution of radioactivity in the organs and tissues of rats, 168 hours after oral administration of 14 C-labelled substance.

Organ or tissue	14C-content as test substance, mean ± SD (mcg/g or mcg/ml)
Blood	0.07 ± 0.02
Plasma	0.03 ± 0.01
Heart	0.54 ± 0.30
Aorta	0.09 ± 0.02
Lungs	0.05 ± 0.04
Brain	0.01 ± 0.01
Nerva	0.05 ± 0.02
Eye	0.03 ± 0.01
Adrenals	0.07 ± 0.01
Thyroid gland	0.21 ± 0.12
Thymus	0.02 ± 0.00
Salivary gland	0.02 ± 0.01
Testes	0.03 ± 0.01
Spleen	0.04 ± 0.01
Bone marrow	0.07 ± 0.02
Muscle	0.03 ± 0.01
Skin	0.05 ± 0.02
Fat (white)	0.11 ± 0.05
Fat (brown)	0.15 ± 0.06
Pancreas	0.04 ± 0.01
Liver	0.14 ± 0.03
Kidneys	0.13 ± 0.03
Stomach	0.07 ± 0.04
Small intestine	0.06 ± 0.04

Table 2. Excretion of radioactivity in urine and faeces of rats after oral administration of the 14C-labelled substance.

Time intervals (h)	Elimination in % of administered radioactivity (mean) in
	urine	faeces	Urine + faeces
0-6	1.20	26.27	37.23
6-24	9.76
24-48	12.03	23.66	35.69
48-72	6.68	5.58	12.26
72-96	3.20	2.87	6.07
96-120	1.09	1.79	2.88
120-144	0.50	0.64	1.14
144-168	0.31	0.54	0.85
Total (0-168)	37.74	61.35	96.12