2,6-diisopropylnaphthalene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Alkylnaphthalenes. I. Absorption, Tissue Distribution and Excretion of 2,6-Diisopropylnaphthalene in Rats

Author:

Kojima S, Nakagawa M, Suzuki R, Horio M, and Tanaka Y

Year:

1978

Bibliographic source:

Chem Pharm Bull 26(10), 3007-3009,

Report date:

1978

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

toxicokinetic study in rats; investigation of absorption, tissue distribution and elimination/excretions after oral administration of single doses

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,6-diisopropylnaphthalene

EC Number:

246-045-1

EC Name:

2,6-diisopropylnaphthalene

Cas Number:

24157-81-1

Molecular formula:

C16H20

IUPAC Name:

2,6-diisopropylnaphthalene

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 230 - 270 g
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on exposure:

2,6-DIPN was administered as solution in olive oil (40 mg/mL)

Duration and frequency of treatment / exposure:

Administration of one single dose

Doses / concentrations

Dose / conc.:

100 mg/kg bw/day (nominal)

No. of animals per sex per dose / concentration:

3 to 5 animals

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, liver, kidney, spleen, heart, brain, muscle, skin, adipose tissue
- Time and frequency of sampling: 2, 4, 6, 8, 14, 24, and 48 h after administration
- Other: rats were sacrificed at each designated time period by decapitation and the tissues collected

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

Toxicokinetic / pharmacokinetic studies

Details on absorption:

After a single dose, ca. 85 % of the dose administered was resorbed within 48 h. Maximal blood level were reached after ca. 2 h. The first-order rate constant for the gastrointestinal absorption of 2,6-DIPN was computed to be 0.170 per h. Overall, the gastrointestinal absorption of 2,6-DIPN appears to be considerably rapid.

Details on distribution in tissues:

Maximal levels of 2,6-DIPN in liver and kidney were reached after 2 h, as it was seen for the other tissues except skin and adipose tissue. Then 2,6-DIPN levels decreased with time. Maximum levels in skin and fat were reached after 10 hours and then levels decreased slowly. The highest maximum DIPN concentrations were found in adipose tissue followed in descending order by skin > liver > heart, kidney, brain > spleen > muscle.
Ca. 10 % (8 %) of the dose was transiently accumulated in adipose tissue after 10 h (24 h) p.a.

Details on excretion:

Excretion of unchanged 2,6-DIPN in feces amounted to ca 3.76 mg (about 15% of the dose) during 48 h. However, this fraction is not attributed to biliary excretion of ingested 2,6-DIPN.
Excretion of 2,6-DIPN in urine was marginal and most notable during the first 24 h.

Metabolite characterisation studies

Metabolites identified:

no

Applicant's summary and conclusion

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results
After oral administration, 2,6-DIPN is resorbed by 85% within 48 h. The remainder is excreted in feces. Peak levels in blood and most tissues are reached within 2 h and largely eliminated after 24 h. In adipose tissue and skin, maximum levels are obtained 10 h p.a. Elimination is slow. After 10 and 24 h ca. 10 % and 8 %, respectively, of the dose are transiently accumulated in adipose tissue.