[No public or meaningful name is available]

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

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other: Non GLP, non guideline, animal experimental study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.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

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

77-73-6

Molecular formula:

C10H12

Constituent 2

Reference substance name:

Dicyclopentadiene

IUPAC Name:

Dicyclopentadiene

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Dicyclopentadiene (DCPD)
- Physical state: waxy solid, liquefied on slight warming
- Analytical purity: 98-99% pure dicyclopentadiene
- Impurities (identity and concentrations): Trace - one may be the cis-form
- Lot/batch No.: LBI No. 763A
- Analysis by UC-W98 column. Retention time was 1.9 minutes (trace impurities noted at approximately 1.5 and 2.1 minutes)

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

dog

Strain:

Beagle

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Laboroatories, Cumberland, Virginia, USA
- Weight at study initiation: 7.6 - 8.9 kg
- Fasting period before study: 18 h
- Housing: individually in stainless steel metabolism cages
- Individual metabolism cages: yes
- Diet : Purina Dog 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: unspecified

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
- 53 mg dicyclopentadiene-14C diluted with 600 mg non-radioactive dicyclopentadiene to form stock.
- dosing solution prepared in corn oil and contained 50 mg dicyclopentadiene-14C (specific activity 0.04 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:

5

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood, urine, faeces, spleen, lungs, heart, liver, kidneys, testes, brain, abdominal muscle, fat, urinary bladder, adrenals, eyes, femur, skin, gall bladder, small intestine, large intestine, caecum, stomach., medulla, cerebrum, cerebellum, thyroid, lymph nodes, spinal cord, bone marrow, pancreas, pituitary, bile, lens, cornea, ocular fluid and ocular tissue.,
- Time and frequency of sampling: urine and faeces collected from individual dogs for each 24 h period until all were killed.
Blood samples collected from femoral vein 0.5, 1, 2, 4, 6, 10 and 24 hours after dosing with DCPD-14C and then at each subsequent 24 hour interval until all dogs were killed.

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 39.9 µg/ml at 2 h. Concentrations were greater in plasma than blood. Elimination from plasma was biphasic with half lives of 10 and 18h.

Details on distribution in tissues:

Radioactivity was widely distributed, Cmax at 4-24 hours, highest concentrations were in the bile, gall bladder, bladder and stomach. Radioactivity was still detectable in most tissues at 7 days.

Details on excretion:

The primary route of excretion of 14C was via urine. 85% of radioactivity was recovered within 72 h with approximately 81% in urine.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Urine contained 6 radioactive constituents; the major polar constituent accounted for 81% of the total radioactivity. No DCPD was detected. Conjugates were present.

Any other information on results incl. tables

The distribution of radioactivity in the eye was assessed. The highest levels were in all parts of the eye at 4 h. After that time, radioactivity was greatly reduced but was still detected in all parts of the eye at 7 days.

Applicant's summary and conclusion

Conclusions:

DCPD was rapidly absorbed, radioactivity was widely distributed into tissues. Elimination from plasma was biphasic with half lives of 10 and 18 hours. Excretion was primarily in urine; a total of 85% of radioactivity was recovered within 72 h with approximately 81% in urine. 6 radiolabelled constituents were separated in the 0-24h urine collection; these included conjugates but no DCPD. There may be some biliary excretion in dogs.

Executive summary:

This study reports the rates of absorption, tissue distribution, metabolism and rate of excretion of 14C labelled dicyclopentadiene. DCPD was rapidly absorbed after oral administration to dogs. Peak plasma levels of 39.9ug/ml occurred in 2 hours. Concentrations were greater in plasma than blood. Elimination from plasma was biphasic with half lives of 10 and 18h.The distribution of radioactivity in the eye was assessed. The highest levels were in all parts of the eye at 4 h. The test substance was widely distributed in other organs at 1 to 2 hours (Cmax at 4-24 hours) with the highest levels in gall bladder and bile. Radioactivity was greatly reduced but was still detected in all parts of the eye at 7 days. Excretion appeared to be primarily via the urine. About 85% of the administered radioactivity was accounted for in urine and faeces within 24 hours. Urine contained 6 radioactive constituent; the major polar constituent accounted for 81% of the total radioactivity. No DCPD was detected. Conjugates were present.