Docosane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

other information

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not GLP and no guideline followed but well conducted and well described study.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not GLP and no guideline followed but well conducted and well described study.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Objective of study:

distribution

Qualifier:

no guideline available

GLP compliance:

no

Remarks:

Not specified

Radiolabelling:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: EVIC CEBA, Guainville, France
- Weight at study initiation: 200 g
- Housing: no data
- Diet (e.g. ad libitum): standard diet (fish flour) ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
no data

Route of administration:

oral: feed

Vehicle:

arachis oil

Details on exposure:

No data

Duration and frequency of treatment / exposure:

Préliminary experiment: daily for 7 days
Main experiment: daily for 6 months

Remarks:

Doses / Concentrations:
Preliminary experiment: 15 mg/day
Main experiment: 0.1%

No. of animals per sex per dose / concentration:

Preliminary experiment: 3 rats
Main experiment: 30 rats periodically sacrified in groups of 3

Control animals:

yes, concurrent no treatment

Positive control reference chemical:

None

Details on study design:

30 animals were fed at 0.1% icosane for 6 months. Then, 2 groups were made: one fed with standard diet and one with energy-restricted diet.

Details on dosing and sampling:

Preliminary experiment: the 3 rats were sacrified the 10th day and liver, spleen, heart, kidneys, lungs, muscle and fat were collected. The rest of the carcass was grinded and lyophilised.
Main experiment: groups of 3 animals were sacrified at 8, 15 days and 1, 2, 3 and 6 months. Icosane administration was stopped 3 days before. Mesenteric and epididymal adipose tissue, liver and muscles from the hind limbs were collected. The rest of the carcass was grinded and lyophilised.

Statistics:

None

Preliminary studies:

Adipose tissue is the main site of retention, corresponding to 7.2% of the total amount of icosane ingested (see table 1).

Details on absorption:

No data

Details on distribution in tissues:

Icosane preferentially locates in fat and its increase parallels the increase in total fat due to growth. Icosane / total fat ratio is rather constant, between 6 to 8 ppm/g.

Details on excretion:

Repeated administration of icosane for several months led to retained amounts corresponding to 6.6% of the total amount ingested.
Icosane was slowly eliminated as after 6 months of "recovery", only 1/3 of icosane was eliminated from fat tissue. In light fed rats, icosane was mobilised as concentration in fat drastically increased in the first months but was no more detectable at 6 months.

Metabolites identified:

no

Details on metabolites:

No data

Table 1: Icosane content in tissues and organs in the preliminary experiment

	Icosane (µg/g of fresh tissue)
Liver	2.6
Heart	3.6
Spleen	13.5
Lungs	11.8
Kidneys	24.5
Muscle	34.3
Fat	317.0

Table 2: Icosane content in tissues and organs during prolonged exposure

	Live weight   (g)	Total lipids   (g)	Total carcass   (µg of icosane / g of tissue)	Liver   (µg of icosane / g of tissue)	Muscle   (µg of icosane / g of tissue)	Fat   (µg of icosane / g of tissue)
0.1% icosane in diet
8 days	264	35.9	63	54.7	17.4	266
15 days	359	574	84	3.3	31.3	374
1 month	342	61	116	4.7	24.2	494
2 months	460	94.8	259	4.7	28.1	684
3 months	509	110.3	373	10.7	56.8	1 029
6 months	580	154	635	17.2	64.1	1 172
Light diet
4 months	336	24	471	8.0	299	8 559
6 months	316	12.7	162	1.7	40.8	‑
Standard diet
6 months	571	148.7	353	10.1	59.7	738.4

Conclusions:

Interpretation of results: high bioaccumulation potential based on study results
Carcass retention of the amounts ingested is about 7%; preferential fixation occurs in adipose tissue.

Only 1/3 of the amount stored in fat disappears in 6 months.

If the animals are fed an energy-restricted diet, mobilization of stored hydrocarbon, although more pronounced, occurs at a lower rate than stored lipid mobilization.

Executive summary:

Accumulation of eicosane was observed over 6 months in rats fed a diet containing 0.1% of icosane. At 6 months, carcass retention of the amounts ingested is about 7%; preferential fixation occurs in adipose tissue. If hydrocarbon administration is discontinued, mobilization is slow since only 1/3 of the amount stored disappears in 6 months. Finally, if the animals are fed an energy-restricted diet, mobilization of stored hydrocarbons, although more pronounced, occurs at a lower rate than stored lipid mobilization.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1975

Materials and methods

Objective of study:

distribution

Test guideline

Qualifier:

no guideline available

GLP compliance:

no

Remarks:

Not specified

Test material

Test material information

Constituent 1

Reference substance name:

Icosane

EC Number:

204-018-1

EC Name:

Icosane

Cas Number:

112-95-8

Molecular formula:

C20H42

IUPAC Name:

icosane

Details on test material:

- Name of test material (as cited in study report): eicosane
- Analytical purity: analytical quality

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: EVIC CEBA, Guainville, France
- Weight at study initiation: 200 g
- Housing: no data
- Diet (e.g. ad libitum): standard diet (fish flour) ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

arachis oil

Details on exposure:

No data

Duration and frequency of treatment / exposure:

Préliminary experiment: daily for 7 days
Main experiment: daily for 6 months

Doses / concentrations

Remarks:

Doses / Concentrations:
Preliminary experiment: 15 mg/day
Main experiment: 0.1%

No. of animals per sex per dose / concentration:

Preliminary experiment: 3 rats
Main experiment: 30 rats periodically sacrified in groups of 3

Control animals:

yes, concurrent no treatment

Positive control reference chemical:

None

Details on study design:

30 animals were fed at 0.1% icosane for 6 months. Then, 2 groups were made: one fed with standard diet and one with energy-restricted diet.

Details on dosing and sampling:

Preliminary experiment: the 3 rats were sacrified the 10th day and liver, spleen, heart, kidneys, lungs, muscle and fat were collected. The rest of the carcass was grinded and lyophilised.
Main experiment: groups of 3 animals were sacrified at 8, 15 days and 1, 2, 3 and 6 months. Icosane administration was stopped 3 days before. Mesenteric and epididymal adipose tissue, liver and muscles from the hind limbs were collected. The rest of the carcass was grinded and lyophilised.

Statistics:

None

Results and discussion

Preliminary studies:

Adipose tissue is the main site of retention, corresponding to 7.2% of the total amount of icosane ingested (see table 1).

Toxicokinetic / pharmacokinetic studies

Details on absorption:

No data

Details on distribution in tissues:

Icosane preferentially locates in fat and its increase parallels the increase in total fat due to growth. Icosane / total fat ratio is rather constant, between 6 to 8 ppm/g.

Details on excretion:

Repeated administration of icosane for several months led to retained amounts corresponding to 6.6% of the total amount ingested.
Icosane was slowly eliminated as after 6 months of "recovery", only 1/3 of icosane was eliminated from fat tissue. In light fed rats, icosane was mobilised as concentration in fat drastically increased in the first months but was no more detectable at 6 months.

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

No data

Any other information on results incl. tables

Table 1: Icosane content in tissues and organs in the preliminary experiment

	Icosane (µg/g of fresh tissue)
Liver	2.6
Heart	3.6
Spleen	13.5
Lungs	11.8
Kidneys	24.5
Muscle	34.3
Fat	317.0

Table 2: Icosane content in tissues and organs during prolonged exposure

	Live weight   (g)	Total lipids   (g)	Total carcass   (µg of icosane / g of tissue)	Liver   (µg of icosane / g of tissue)	Muscle   (µg of icosane / g of tissue)	Fat   (µg of icosane / g of tissue)
0.1% icosane in diet
8 days	264	35.9	63	54.7	17.4	266
15 days	359	574	84	3.3	31.3	374
1 month	342	61	116	4.7	24.2	494
2 months	460	94.8	259	4.7	28.1	684
3 months	509	110.3	373	10.7	56.8	1 029
6 months	580	154	635	17.2	64.1	1 172
Light diet
4 months	336	24	471	8.0	299	8 559
6 months	316	12.7	162	1.7	40.8	‑
Standard diet
6 months	571	148.7	353	10.1	59.7	738.4

Applicant's summary and conclusion

Conclusions:

Interpretation of results: high bioaccumulation potential based on study results
Carcass retention of the amounts ingested is about 7%; preferential fixation occurs in adipose tissue.

Only 1/3 of the amount stored in fat disappears in 6 months.

If the animals are fed an energy-restricted diet, mobilization of stored hydrocarbon, although more pronounced, occurs at a lower rate than stored lipid mobilization.

Executive summary:

Accumulation of eicosane was observed over 6 months in rats fed a diet containing 0.1% of icosane. At 6 months, carcass retention of the amounts ingested is about 7%; preferential fixation occurs in adipose tissue. If hydrocarbon administration is discontinued, mobilization is slow since only 1/3 of the amount stored disappears in 6 months. Finally, if the animals are fed an energy-restricted diet, mobilization of stored hydrocarbons, although more pronounced, occurs at a lower rate than stored lipid mobilization.