2-chlorobenzaldehyde

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

Deviations:

yes

Remarks:

only one dose level per route tested

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
- Analytical purity: 98%

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TNO stock, Zeist (The Netherlands)
- Age at study initiation: 6 weeks
- Weight at study initiation: 180 - 200g
- Fasting period before study:
- Housing: 3 days prior to experiments the rats were housed in individual glass metabolism cages 30 cm designed to separate urine from faeces
and to trap expired air.
- Individual metabolism cages: yes
- Diet and water ad libitum

Air was drawn through the metabolism cage (volume 24 l) at a rate of 400 ml/min by means of a peristaltic pump, so that the pressure inside the cage was somewhat lower than outside . This air was led from the metabolism cage subsequently through three gaswashing bottles ; the first one was empty and put on ice to trap expired water ; the next two bottles contained 20% water in ethanolamine (v/v) to traexpired CO2. The trap solution was renewed every 6 hours.

Administration / exposure

Type of coverage:

other: glass cup

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 h

Doses:

75 µl/kg ; 1 .83 mCi/ml

No. of animals per group:

8

Details on study design:

DOSE PREPARATION
- Method for preparation of dose suspensions: The specific activity of the compound was 740 MBq/mmol (20 mCi/mmol) and was reduced by addition of pure unlabelled material to 10.2 MBq/mmol (0.275 mCi/mmol). Radiochemical purity was at least 98%.

APPLICATION OF DOSE: The radiolabelled benzaldehyde (dose 75 ltl/kg ; 1 .83 mCi/ml) was pipetted undiluted in the cup, which was closed immediately afterwards with a glass-cover using a cyanoacrylate adhesive .

TEST SITE
- Preparation of test site: 16 hrs before topical applications of 1°C- 2-chlorobenzaldehyde, hair on a part of the right dorsal area was shaved with clippers. Then a glass cup was fixed to the shaved ratskin with cyanoacrylate adhesive 1 hour before the start of the experiment. The cup was glued in such a way that no contact between the glass or the adhesive with the treated skin was possible .
- Type of cover / wrap if used: The cup on the animal was fixed by two pieces of crossed elastic adhesive bandages of 1 cm width. Then crepebandage and elastic adhesive bandage was wound around the animal in such a way as not to hinder its respiration.

SAMPLE COLLECTION
- Collection of blood: collected from femoral artery at time intervals during the experimental period of 72 h
- Collection of urine and faeces: urine collected at regular time intervals for 72 h after application; faeces collected quantitatively at daily intervals
- Collection of expired air: Samples from the gas-washing bottles taken frequently via syringe-connected catheters without interruption of air flow

ANALYSIS
- radioactivity was measured using a liquid scintillation counter, Packard TRICARB model 460 CD. The counting efficiency was determined by an
internal standard.
- Blood samples: fractionated in plasma and cells, stored at 4°C for less than 6 h; bloodplasma dissolved and counted in Instagel/0 .5 M HCI (9 :1, v/v); erythrocytes dissolved (mixture of soluene 350 and 2-propanol (1 : 1, v/v)), bleached (35% hydrogen peroxide) and counted in Instagel/0.5 M
HCI (9 :1, v/v).
- Urine and ethanolamine-C02 samples: weighed; counted directly in scintillation liquid (Instagel); Weighed samples of feaces - homogenized;. Aliquots dissolved in soluene 350 at 50°C for 2 h, cooled at 4°C for 5 min, mixed with 2-propanol, bleached with 35% hydrogen peroxide, counted in Instagel/0 .5 M HCI (9 : I, v/v).
- glass-cup rinsed with methanol, rinsing fluids collected in glass-scintillation vials until counting (Instagel).
- exposed skin: widely excised, cut into small pieces, solubilized in Soluene 350 at 50°C for 2 h . After cooling 2- propanol was added and the mixture was bleached (35% hydrogen peroxide). Duplicate samples were counted.
- qualitative and quantitative determination of metabolites in urine with a thin layer chromatography- radioautography method.

Results and discussion

Signs and symptoms of toxicity:

no effects

Percutaneous absorption

Dose:

4000-6000 dpm/g

Parameter:

percentage

Absorption:

ca. 0.1 %

Remarks on result:

other: 10-15 h post dosing

Any other information on results incl. tables

Cutaneously administered 14C-2-chlorobenzaldehyde (75 µI/kg) was well absorbed by the skin of rats as indicated by plasma radioactivity levels and the high total recovery of radioactivity. The slow increase in plasma-radioactivity was shown in all cutaneous experiments and the peak plasma concentrations of 4000-6000 dpm/g were reached 10 -15 h post dosing. Thereafter the plasma-radioactivity declined slowly with a 14C half-life ranging between 20 and 40 h.

The major portion of radioactivity was excreted in the urine. Small amounts were found in the faeces and in the exhaled air. The cutaneously administered radioactivity was mainly recovered from urine, faeces and glasscup over a 3-day period. Urinary excretion of the radioactivity was found about 45% within the first 24 h post dosing: About 15% of the 75 µl/kg dose of 14C-2-chlorobenzaldehyde was found in the glasscup and on the skin. The exhalation of 14C02 over a period of 72 h was minimal, approximately 1% of the dose.

The principal metabolite in rat urine was 2-chlorohippuric acid . The radioactivity derived from 14C-2-chlorobenzyl alcohol was mostly excreted in the second-day urine of the cutaneously treated rats. About 15% of the total urinary radioactivity was eliminated as 2-chlorobenzyl alcohol and 2-chlorobenzoic acid into urine within 72 h (cutaneous).

No radioactivity was retained in the red blood cells after administration of 14C-2-chlorobenzaldehyde .