3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP, non guideline, animal experimental study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Rates of absorption, tissue distribution, metabolism and rate of excretion of 14C labelled dicyclopentadiene

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

3a,4,7,7a-tetrahydro-4,7-methanoindene

EC Number:

201-052-9

EC Name:

3a,4,7,7a-tetrahydro-4,7-methanoindene

Cas Number:

77-73-6

Molecular formula:

C10H12

IUPAC Name:

3a,4,7,7a-tetrahydro-1H-4,7-methanoindene

Constituent 2

Reference substance name:

Dicyclopentadiene

IUPAC Name:

Dicyclopentadiene

Details on test material:

- Name of test material (as cited in study report): Dicyclopentadiene (DCPD -14C)
- Physical state: uniformly labelled with 14C
- Analytical purity of stock: 97%
- Lot/batch No.: 895-157
- Radiochemical purity (if radiolabelling): 99%
- Specific activity (if radiolabelling): 3.02 µCi/mM
- Other: Total quantity of 53 mg dicyclopentadiene-14C was diluted with 600 mg nonradioactive dicyclopentadiene to form stock used for all pharmacokinetic and metabolism studies.

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not reported
- Age at study initiation:
- Weight at study initiation: 180-280 g
- Fasting period before study: 18 h
- Housing: individually in Roth metabolism cages
- Individual metabolism cages: yes
- Diet :.Purina Rat chow (ad libitum)
- Water: ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS: Not reported

IN-LIFE DATES: Not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
- 53 mg DCPD-14C diluted with 600 mg non-radioactive dicyclopentadiene to form stock.
- dosing solution prepared in corm oil and contained 20 mg dicyclopentadiene-14C (specific activity 0.20 µCi/mg) per mL corn oil.

Duration and frequency of treatment / exposure:

Single dose

Doses / concentrations

Remarks:

Doses / Concentrations:
100 mg/kg bw.

No. of animals per sex per dose / concentration:

12

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood, urine, faeces, expired carbon dioxide , spleen, lungs, heart, liver, kidneys, testes, brain, abdominal muscle, fat, urinary bladder, adrenals, eyes, femur, skin, gall bladder, small intestine, large intestine, caecum and stomach.,
- Time and frequency of sampling: urine, faeces and expired carbon dioxide collected for 24 h and then every 24 h thereafter until all were killed.
Blood samples collected from aorta from 2 rats/time period, killed at 2, 4, 6, 24, 48 and 72 hours after dosing with dicyclopentadiene-14C.
- Other: Expired carbon dioxide was absorbed by a mixture containing ethanolamine:methyl cellusolve:toluene (1:8:10v/v)

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled : urine
- Time and frequency of sampling: 0 - 24 h
- From how many animals: 2 per time point (samples pooled)
- Method type(s) for identification: TLC
- Other: Radioactive spots on the TLC plates were localised by scanning with a radiochromatogram scanner.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Absorption was rapid, Cpmax was 23.28 µg/ml at 6 h. Concentrations were greater in plasma than blood. Elimination from plasma was biphasic, the terminal half life was 27h.

Details on distribution in tissues:

Radioactivity was widely distributed, Cmax at 2-6 hours, highest concentrations were in the fat, adrenals and urinary bladder. Radioactivity was still detectable in all tissues at 72 hours.

Details on excretion:

The primary route of excretion of 14C was via urine. 94% of radioactivity was recovered within 72 h with approximately 75% in urine.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Urine contained 7 radioactive components; the major polar component accounted for 41% of the total radioactivity. No DCPD was detected. Conjugates were present.

Any other information on results incl. tables

Average plasma and whole blood levels (µg/ml) of 14 C radioactivity in rats after a single oral dose of dicyclopentadiene-14C

Time point (post dose)	15 m	30 m	1 h	2 h	4 h	6 h	24 h	48 h	72 h
Blood	-	-	-	10.65	11.92	19.76	14.09	1.93	0.47
Plasma	-	-	-	11.51	14.44	23.28	15.47	2.13	0.36

Key: m = minutes, h = hour

Applicant's summary and conclusion

Conclusions:

Dicyclopentadiene was rapidly absorbed, radioactivity was widely distributed into tissues. The terminal elimination half life from plasma was 27 hours. Excretion was primarily in urine; a total of 94% of radioactivity was recovered within 72 h with approximately 75% in urine. 7 radiolabelled components were separated in the 0-24h urine collection; these included conjugates but no dicyclopentadiene.