Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not GLP and no international guideline followed. No recovery but this study gives valuable information about hydrocarbon distribution after prolonged exposure.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1981

Materials and methods

Objective of study:
distribution
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
In order to study the distribution of octadecane, male rats were fed 0.1 mg/animal/day 14C-octadecane for 90 days. The animals were killed at 5, 11, 15, 20, 29, 46, 60, 75, and 90 days after beginning of exposure and radioactivity in different organs was measured.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): octadecane
- Specific activity (if radiolabelling): 185 000 000 Bq/kg
- Locations of the label (if radiolabelling): 1 C
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
other: white
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 260-280 g

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: sunflower oil
Details on exposure:
Concentration of radioactivity in vehicle: 37 000 Bq/mL.
Duration and frequency of treatment / exposure:
Daily for 90 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1 mg corresponding to 18 500 Bq
No. of animals per sex per dose:
86
Control animals:
no
Positive control:
None
Details on study design:
No data
Details on dosing and sampling:
The animals were killed at 5, 11, 15, 20, 29, 46, 60, 75, and 90 days after beginning of the experiment. Blood, liver, lien, brain, heart, kidneys, adrenal glands, testicles, muscular and fatty tissues samples as well as urine, feces, and exhaled air underwent radiometric tests.
Statistics:
Variance analysis method

Results and discussion

Preliminary studies:
No data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
No data
Details on distribution in tissues:
The highest volume of marker after 5 days of experiment was found in liver followed by adrenal glands, lungs, kidneys, lien, muscles, heart, brain, testicles, and excluding fatty tissue (Table 1). The lowest volume of marker was found in blood. Amounts of radioactivity gradually increased in all organs except in liver. At 90 days, the highest amount of radioactivity was found in adrenal glands, corresponding to about 30% of the total radioactivity found in organs examined.
The fatty tissue radioactivity was the highest, and increased gradually till 60-th day of the experiment; it even more sharply increased after, with only about 10-20% of radioactivity corresponding to the unchanged form, octadecane (table 2).
Gradual increase in octadecane content took place in blood, kidneys, and muscles (table 3). Octadecane in liver varied maybe due to periodical enzyme induction.
Details on excretion:
Octadecane was not eliminated in urine. Hydrocarbon activity in feces was approximately the same as its total radioactivity (Table 3).

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
No data

Any other information on results incl. tables

Table 1: Radioactivity of rats’ organs and tissues in different periods after beginning of oral administration of labeled octadecane (in imp/min peror 1 mL of biosample)

Organ

Day

5th

11th

15th

20th

46th

60th

75th

90th

Blood

1690±60

1310±58

1300±60

1350±64

2350±155

2660±160

4090±365

3590±360

Liver

18240±535

22090±850

18010±740

9300±495

24080±1600

24890±1800

74900±7100

66880±6400

Muscle

5660±184

6700±185

3830±170

5220±250

11400±760

9340±660

19140±1700

17560±1700

Lien

8210±310

7240±300

5650±285

7760±390

14620±890

17010±1020

38330±2400

25470±2100

Lungs

11270±390

12200±440

7490±320

14470±580

25130±1800

37710±2900

35120±3230

32460±3210

Kidneys

9120±310

9050±300

11830±450

8320±350

32660±2000

25320±1800

30120±2500

37350±3200

Brain

4750±140

4360±140

4440±180

4280±170

4640±280

6910±490

11430±910

12850±1180

Heart

5500±185

6540±190

8650±340

14140±560

21440±1400

17410±1400

41030±3700

30590±2900

Testicles

3660±110

3500±120

3160±110

4230±160

9030±540

8630±610

11610±1020

10140±1100

Adrenal glands

12470±370

10400±330

9410±380

10000±410

66340±3800

83570±5240

161440±11240

112950±9450

Table 2: Total radioactivity of rats’ fatty tissue and radioactivity of octadecane isolated from it (in imp/min perof tissue; M±m)

Day

Total radioactivity

Octadecane radioactivity

5th

147190±6360

10000±310

11th

153100±7380

11700±410

15th

171700±9410

12300±525

20th

182670±10440

13400±630

29th

179860±12430

31700±1800

46th

246470±17490

56910±3240

60th

535100±37720

86330±7290

75th

727190±66860

166000±17410

90th

1412240±161200

155100±17390

Table 3: Octadecane content in rats’ biomaterial at its long-term administration (in imp/min peror 1 ml of biosample; M±m )

Biosample

Day

5th

11th

15th

20th

46th

60th

75th

90th

Blood

30±6

40±7

90±10

96±12

250±18

370±21

420±24

430±26

Liver

2400±150

650±30

410±25

340±22

2390±160

2740±226

4300±470

3740±460

Muscle

520±23

740±39

590±35

1350±95

3200±256

3560±260

4100±460

4420±568

Kidneys

500±22

820±40

1200±75

1160±86

2450±150

2700±254

3800±362

4100±366

Feces

7600±786

ND

ND

ND

13450±1800

16130±2200

ND

ND

Urine

0

0

0

0

0

0

0

0

ND: Not Determined

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results Octadecane is a lipophilic compound that permeates through membranes, but at slow rates due to its low solubility in water layers. It is the slow rate of elimination that gives such a high log Kow-chemical its inherent bioaccumulative potential.
Octadecane gradually accumulates in rats' organs and tissues when orally administered on the amount of 0.1 mg/day per animal during 90 days; the highest accumulation occurred in fatty tissue. Octadecane is not discharged with urine. Biotransformation of octadecane occurs in rats’ bodies with CO2 production, however, it happens at low rate. The metabolism products are characterized by high tropism to fatty tissues. The low rate of dynamic equilibrium establishment (about 60 days) shows that octadecane is included inside tissues and has low rate exchange.
Executive summary:

In order to study the distribution of octadecane, male rats were fed 0.1 mg/animal/day 14C-octadecane for 90 days. The animals were killed at 5, 11, 15, 20, 29, 46, 60, 75, and 90 days after beginning of exposure and radioactivity in different organs was measured.

The highest volume of marker after 5 days of experiment was found in liver followed by adrenal glands, lungs, kidneys, lien, muscles, heart, brain, testicles, and excluding fatty tissue. The lowest amount of marker was found in blood. Amounts of radioactivity gradually increased in all organs except in liver. At 90 days, the highest amount of radioactivity was found in adrenal glands, corresponding to about 30% of the total radioactivity found in organs examined.

The fatty tissue radioactivity was the highest, and increased gradually till 60-th day of the experiment; it even more sharply increased after, with only about 10-20% of radioactivity corresponding to the unchanged form, octadecane.

Gradual increase in octadecane content took place in blood, kidneys, and muscles. Octadecane in liver varied maybe due to periodical enzyme induction but was not eliminated in urine.