2-chlorobenzaldehyde

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

year of publication: 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Sufficently documented literature data

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Percutaneous absorption of 14C-labelled 2-chlorobenzaldehyde in rats. Metabolism and toxicokinetics.

Author:

Rietveld EC, Hoet RMA, Seutter-Berlage F, van Rossum JM

Year:

1988

Bibliographic source:

European Journal of Drug Metabolism and Pharmacokinetics 13: 231-240

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

investigation of metabolism in vivo

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-chlorobenzaldehyde

EC Number:

201-956-3

EC Name:

2-chlorobenzaldehyde

Cas Number:

89-98-5

Molecular formula:

C7H5ClO

IUPAC Name:

2-chlorobenzaldehyde

Details on test material:

- Name of test material (as cited in study report): 2-chlorobenzaldehyde
- Radiochemical purity (if radiolabelling): at least 98%
- Specific activity (if radiolabelling): 20 mCi/mmol; reduced to 0.275 mCi/mmol by addition of pure unlabelled material
- Locations of the label (if radiolabelling): carbonyl-group

Radiolabelling:

yes

Remarks:

2-Chloro(carbonyl-14C)benzaldehyde

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

- Source: TNO, Zeist (The Netherlands)
- Age at study initiation: about 6 weeks
- Individual metabolism cages: yes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least three days prior to experiments rats were housed in individual glass metabolism cages
- Air was drawn through the metabolism cage (volume 24 l) at a rate of 400 ml/min; pressure inside the cage was somewhat lower than outside
- polyethylene catheters (I.D. 0.4 mmmm; O.D. 0.8 mm) were placed into the femoral artery and the jugular vein and led subcutaneously to the nuchal area where they went out of the body

Administration / exposure

Route of administration:

other: dermal, intravenous, intraperitoneal

Vehicle:

water

Details on exposure:

DERMAL EXPOSURE:
Preparation of dose:
- radiolabelled substance was pipetted undiluted in the cup, which was closed immediatly afterwards with a glass cover using the cyanoacrylate adhesive

TEST SITE
- Preparation of test site: shaved, 16 hours before application
- Area of exposure: right dorsal skin,
- Type of cover: with a glass cup (I.D. 16 mm, O.D. 24 mm, height: 10 mm) which was fixed to the skin with cyanoacrylate adhesive; the cup was glued in such a way that no contact between the glass or the adhesive with the treated skin was possible.


SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes: glass cup

REMOVAL OF TEST SUBSTANCE
- Washing procedures and type of cleansing agent: the glass was rinsed with methanol
- exposed skin was widely excised, cut into small pieces and solubilized bevor counting of radioactivity


SAMPLE COLLECTION
- Collection of blood: from femural artery
- Collection of urine and faeces: urine was colleted for 72 hours after the administration; faeces was collected at daily intervals

INTRAVENOUS AND INTRAPERITONEAL EXPOSURE:

25 µl/kg bw of the radiolabelled test substance (specific radioactivity 1.83 mCi/ml dissolved in 1 ml of 2% aqueous solution of Tween-60) were injected into the jugular vein catheter, duration about 4 minutes; 37.5 µl/kg were applied intraperitoneally.

Duration and frequency of treatment / exposure:

72 hours (dermal application)
single exposure (i.v. and i.p. application)

Doses / concentrations

Remarks:

Doses / Concentrations:
75 µl/kg (dermal application)
25 µl/kg (i.v. application)
37.5 µl/kg (i.p. application)

No. of animals per sex per dose / concentration:

8 (dermal application),
6 (i.v. application),
2 (i.p application)

Control animals:

no

Positive control reference chemical:

none

Details on dosing and sampling:

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: dermal application: 0-12 h, 12-24 h, 24-48 h, 48-72 h; i.v. and i.p. application: 0-6 h, 6-24 h
- From how many animals: no data
- Method type(s) for identification: thin layer chromatography
- Limits of detection and quantification: no data

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

More than 95% of the radioactivity in the urine was ethyl acetate extractable. Metabolic patterns of urinary excreted metabolites of the test item were quite similar after dermal, i.v. and i.p. application, apart from some quantitative differences. None 14C-2-chlorobenzaldehyde was identified in the urine. 2-Chlorohippuric acid was the main metabolite excreted (about 65% to 75% depending on the application route). Additionally, 2-chlorobenzylmercapturic acid, 2-chlorobenzoic acid and 2-chlorobenzyl alcohol were identified as urinary metabolites. 14C-2-chlorobenzyl alcohol was mostly excreted in the urine collected on the second day (24-48 h) of cutaneously treated rats. This metabolite was found in much smaller amounts in the urin of rats which were treated i.v. or i.p. 2-Chlorobenzyl alcohol and 2-chlorobenzoic acid accounted for abour 15% of the total urinary radioactivity.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results concluded by supplier
2-Chlorobenzaldehyde is extensively metabolised in rats. 2-Chlorohippuric acid is the main metabolite. 2-Chlorobenzyl alcohol, 2-chlorbenzoic acid and 2-chlorobenzylmercapturic acid were identified as further metabolites. No unchanged compound was identified in the urine.

Executive summary:

Urinary metabolites of 14C-2-chlorobenzaldehyde were identified in rats treated percutaneously, intravenously or intraperitoneally. The principal metabolite in rat urine was 2-chlorohippuric acid. Additionally, 2-chlorobenzyl alcohol, 2-chlorobenzoic acid, which accounted for about 15% of urinary radioactivity, and 2-chlorobenzylmercapturic acid were identified in the urine by means of thin layer chromatography. No unchanged compound was detected in the urine.

The study has been judged to be reliable with restrictions (RL2). It was selected as key study.