Octadecane

Basic toxicokinetics

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

Octadecane

EC Number:

209-790-3

EC Name:

Octadecane

Cas Number:

593-45-3

Molecular formula:

C18H38

IUPAC Name:

octadecane

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 or test system 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 / concentration:

86

Control animals:

no

Positive control reference chemical:

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
	5^th	11^th	15^th	20^th	46^th	60^th	75^th	90^th
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
5^th	147190±6360	10000±310
11^th	153100±7380	11700±410
15^th	171700±9410	12300±525
20^th	182670±10440	13400±630
29^th	179860±12430	31700±1800
46^th	246470±17490	56910±3240
60^th	535100±37720	86330±7290
75^th	727190±66860	166000±17410
90^th	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
	5^th	11^th	15^th	20^th	46^th	60^th	75^th	90^th
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.