4-tert-butylpyrocatechol

Basic toxicokinetics

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

Guideline:

OECD Guideline 417 (Toxicokinetics)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butylpyrocatechol

EC Number:

202-653-9

EC Name:

4-tert-butylpyrocatechol

Cas Number:

98-29-3

Molecular formula:

C10H14O2

IUPAC Name:

4-tert-butylbenzene-1,2-diol

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 or test system 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 / concentration:

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	6	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%).