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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Unspecified (results initially published in 2000)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Radioactive labeling: 14-C on the methine carbon
- Radiolabeled compound specific activity: 15.0 mCi/mmol
- Radiochemical purity: approximately 94% (determined by HPLC)
- Radiolabeled batch number: 940207
- Radiolabeled compound provider: Wizard Laboratories (West Sacramento, CA)
- Non-radiolabeled batch number: DF04501LZ
- Non-radiolabeled compound provider: Aldrich Chemical Company, Inc. (Milwaukee, WI)
Radiolabelling:
yes
Remarks:
[14C]-p-tert-butylcatechol

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc. (Raleigh, NC, and Portage, MI)
- Age at study initiation: 9 to 10 weeks old
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: Polycarbonate cages
- Individual metabolism cages: yes (from the day before dosing)
- Diet: Purina Rodent Chow No. 5002
- Water: ad libitum
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
Not specified


IN-LIFE DATES: Not specified

Administration / exposure

Route of administration:
dermal
Vehicle:
other: acetone
Details on exposure:
TEST SITE
- Area of exposure: 1 cm²
- % coverage: Not specified
- Type of wrap if used: metal tissue capsule glued over the dosing site with QuicktiteTM Super Glue Gel
- Time intervals for shavings or clipplings: Clipping approx. 24 hours before dose application


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: up to 72 hours after dosing


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 to 22.2 μCi [14C]-radiolabel and appropriate amount of unlabeled p-tert-butylcatechol
- concentration (if solution): Not applicable


VEHICLE
- Justification for use and choice of vehicle (if other than water): Not specified
- Amount(s) applied (volume or weight with unit): approximately 25 μL
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not specified
- Purity: Not specified


USE OF RESTRAINERS FOR PREVENTING INGESTION: No data
Duration and frequency of treatment / exposure:
single exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
0.04 or 4 mg/animal
No. of animals per sex per dose:
4 males
Control animals:
no
Details on study design:
- Dose selection rationale: dermal doses for mice selected to provide approximately equal concentrations of p-tert-butylcatechol per square centimeter of skin as the 0.6 and 60 mg/kg doses administered to rats.
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)

- Tissues and body fluids sampled: urine, faeces.
- Time and frequency of sampling: once after 72h. Radioactivity was measured in urine collected 6, 24, 48 and 72h after  dosing and feces collected 24, 48 and 72h after dosing (stored in dark at  -20°C until analysis). Skin wash and digests of the application site skin and carcass were  analysed by LSS.

METABOLITE CHARACTERISATION STUDY: no.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Most of the dose was absorbed by 72 hours following application (72% for the 0.04 mg dose and  86% for the 4 mg dose).
Mice applied 4 mg showed signs of local inflammation at the site of application.
Details on distribution in tissues:
Global distribution of radioactivity in tissues, at the application site, in urine and feces (% of dose) is detailed below.
Details on excretion:
Cumulative excretion of radioactivity is detailed below.

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

Cumulative excretion of radioactivity (cumulative % of dose, mean +/- standard deviation):

Dose (mg) Time (h) Urine (%) Feces (%) Total (%)
0.04 4.3 +/- 5.2  - (not collected) 4.3 +/- 5.2 
  24 32.1 +/- 9.6 7.45 +/- 5.39  39.6 +/- 13.6
  48 47.1 +/- 10.7 8.15 +/- 5.31  55.2 +/- 15.3
  72  51.7 +/- 8.9 12.4 +/- 7.7  64.1 +/- 15.7
4 6 11.9 +/- 14.0  - (not collected) 11.9 +/- 14.0
  24  54.3 +/- 10.5 2.58 +/- 1.30 56.9 +/- 10.3
  48  68.3 +/- 3.9 3.48 +/- 1.51 71.8 +/- 3.0 
  72  71.4 +/- 3.5 5.42 +/- 2.55  76.8 +/- 1.4

Distribution of radioactivity at 72 hours (% of dose, mean +/- standard deviation):

 Dose (mg/kg)  Tissues (%)  Application site (%)  Feces (%)  Urine (%)  Total absorbed dose (%)  Total unabsorbed dose (%)
 0.04 11.6 +/- 8.3 1.51 +/- 0.43  12.4 +/- 7.7 57.0 +/- 7.5 72.2 +/- 14.2 11.6 +/- 8.3
 4 0.76 +/- 0.30 6.18 +/- 0.52 5.4 +/- 2.6 73.7 +/- 3.2 86.0 +/- 2.7 2.25 +/- 0.81


Applicant's summary and conclusion

Conclusions:
Bioaccumulation potential cannot be judged based on study results
The absorption, distribution and excretion of 4-tert butylpyrocatechol were studied in mice following a single dermal application of radiolabeled compound.
Executive summary:

Groups of 4 mice were administered a single dermal application of 0.04 or 4 mg/kg 14C-4-tert butylpyrocatechol (TBC).

At 72 hours following application, the total unabsorbed dose was 11.6% or 2.25% from total radioactivity, at 0.04 or 4 mg, respectively.

Most of the excreted radioactivity was retrieved from urine (up to 73.7%).