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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:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test was not performed according to international standardised guidelines and the exposure to cigarette smoke is uncommon.

Data source

Reference
Reference Type:
publication
Title:
Studies on the deposition and distribution of catechol from whole cigarette smoke in B6C3F1/Cum mice
Author:
Hwang K.K., Sonko O., Dansie D.R., Kouri R.E., Henry C.J.
Year:
1982
Bibliographic source:
Toxicology and Applied Pharmacology, 64, 405-414.

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
Exposure to cigarette smoke labelled with 2 to 2.3 µCi of [3H] catechol.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Pyrocatechol
EC Number:
204-427-5
EC Name:
Pyrocatechol
Cas Number:
120-80-9
Molecular formula:
C6H6O2
IUPAC Name:
pyrocatechol
Details on test material:
- [3H]catechol was synthesised and purified using catalytic reduction procedures. The chemical had a specific activity of 2.5 mCi/mmol and purity > 98 %.
- Catechol was from Aldrich Chemical Company, Milwaukee, Wisconsin.

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Cumberland View farms (Clinton, Tennessee)
- Age at study initiation: 4-6 weeks old
No more data

Administration / exposure

Route of administration:
inhalation: aerosol
Vehicle:
other: diluted cigarette smoke
Details on exposure:
TYPE OF INHALATION EXPOSURE: nose only

Tritiated catechol has been used to follow the pharmaco-kinetics and metabolic fate of inhaled catechol in cigarette smoke in BC3F1/cum female mice. The presence of [3H]catechol was verified by silica gel chromatography, high performance liquid chromatography, and gas chromatography/mass spectrometry. Mice were exposed to 10% (v/v) 2R1 cigarette smoke on the Walton Horizontal Smoking Machine under standard conditions of 35 ml puff volume, 2 sec/puff, 10 puffs/cigarette.
The deposition and distribution of inhaled catechol were determined in all internal tissues, urine and faeces at 0, 5, 10, 30, 60 and 120 min.
Four exposure experiments were performed. Twelve mice per time were exposed to catechol (results expressed as the means from 8 mice per death time point).
Twelve mice were exposed to catechol for 2 h. They were killed 2 hours after the end of exposure. Urine and faeces were collected separately.
Six mice were exposed to filtered smoke from one (3H)-catechol 2R1 cigarette.
Duration and frequency of treatment / exposure:
10 minute(s)
Doses / concentrations
Remarks:
Doses / Concentrations:
Mice were exposed to 10% (v/v) 2R1 cigarette smoke on the Walton Horizontal Smoking Machine under standard conditions of 35 ml puff volume, 2 sec/puff, 10 puffs/cigarette.
No. of animals per sex per dose / concentration:
66 females
Control animals:
not specified

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
- Clearance was occurring during the 10-min smoke exposure period.  - Immediately after exposure (t = 0), over 56 % of the radioactivity (in the total body) was found in the blood, 14% in the kidneys, 13% in the liver, 10% in the lung, and approximately 12 % in the respiratory tract. The blood contained the greatest percentage of radioactivity at all times (measured at up to 2 h after exposure). The radioactivity decreased over time in all tissues. Two hours after exposure, approximately 11% of the radioactivity remained in the body.
Details on excretion:
- In another experiment, where urine and faeces were collected, over 91% of the inhaled radioactivity were found in the urine and 1.5% was excreted in the faeces within 2 h after exposure. Less than 1% of the radioactivity remained in the lung, turbinate, liver or kidneys 2 h after exposure. Catechol is rapidly absorbed, redistributed, and excreted from mice exposed to whole cigarette smoke.

Metabolite characterisation studies

Metabolites identified:
not measured

Applicant's summary and conclusion

Conclusions:
No bioaccumulation potential based on study results
Executive summary:

[3H] catechol was used to follow the kinetics and metabolic fate of inhaled catechol in cigarette smoke in Mice. 2 to 2.3 µCi [3H] catechol were present in reconstituted cigarette.

Mice were exposed to 10% (v/v) 2R1 cigarette smoke on nose only and received 35mL puff volume, 2 sec/puff, 10 puffs/cigarette for 0, 5, 10, 30, 60 and 120 minutes. The deposition and distribution of inhaled catechol were determined in all internal tissues, urine and feces. Data showed that cleareance was occuring during the 10 minutes smoke exposure period. Immediately after exposure, over 50% of the radioactivity was found in the blood, with 10% found in the lung, and approximately 12% in the respiartory tract. Over 91% of the inhaled radioactivity was found in the urine 120 minutes after exposure. Less than 0.5% of the total dose was found in the lung at this time. Catechol is rapidly absorbed, redistributed, and excreted from mice exposed to whole cigarette smoke.