Carbon tetrachloride

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Does not meet criteria of today standard methods

Data source

Reference

Reference Type:

publication

Title:

Comparative study of the in vivo percutaneous absorption of chlorinated solvents in mice

Author:

Tsuruta H.

Year:

1975

Bibliographic source:

Industrial Health, vol. 13, p. 227

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

Deviations:

yes

Remarks:

, see "Priciples of method if other than guideline"

Principles of method if other than guideline:

Anesthesized ICR mice were exposed for 15 min to pure CTC at 2.92 cm² of shaved skin. During exposure exhaled CTC was trapped in washing flasks. At the end of exposure animals were sacrificed by CO inhalation, flash frozen, pulverized in a blender and an aliquot of the powder was extracted and analyzed for its CTC content by GC with an electron capture detector (ECD).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Carbon tetrachloride

EC Number:

200-262-8

EC Name:

Carbon tetrachloride

Cas Number:

56-23-5

Molecular formula:

CCl4

IUPAC Name:

tetrachloromethane

Details on test material:

- Name of test material (as cited in study report): tetrachlorormethane
- Physical state: liquid
- Analytical purity: no detectable impurities (by GC FID)
- Lot/batch No.: not reported
- supplier: Wako Pure Chem. Co., Tokyo
- Stability under test conditions: stable
- Storage condition of test material: not reported

Radiolabelling:

no

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not reported
- Age at study initiation: not reported
- Weight at study initiation: 30 - 35 g
- Fasting period before study: not reported
- Housing: not reported
- Individual metabolism cages: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported


IN-LIFE DATES: not reported

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

15 min

Doses:

- Nominal doses: 0.5 mL (= 0.792 g)

No. of animals per group:

6

Control animals:

no

Details on study design:

DOSE PREPARATION
- Method for preparation of dose suspensions: pure substance was used
- Method of storage: pure substance was used


APPLICATION OF DOSE:


VEHICLE
- no vehicle used


TEST SITE
- Preparation of test site: The skin of the abdominal region was clipped with an electric clipper and a small glass funnel was glued with autopolymerized resin "Pile-B" on the skin to delineate an area of 2.92cm².
- Area of exposure: 2.92cm²
- % coverage: not reported
- Type of cover / wrap if used: the glass funnel was covered with a plastic adhesive tape
- Time intervals for shavings or clipplings: shaved once before application

2. 0.5 ml of a test solvent
was applied to this area for a period of 5 to 15 rnin. As soon as the test solvent had
been applied, the glass funnel was closed at the top with a plastic adhesive tape to
avoid evaporation and then the mouse mouth was covered with a mask to collect the
expired breath

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: glass funnel glued to the skin of anesthesized animals


REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: yes, by tearing off from prior sacrificed animals
- Washing procedures and type of cleansing agent: no washing
- Time after start of exposure: 15 min


SAMPLE COLLECTION
- Collection of blood: no
- Collection of urine and faeces: no
- Collection of expired air: yes, by a breathing masks supplied with fresh air on the inlet side and connected on the outlet side to two absorption bottles (15 mL n-hexane each) to trap the test substance
- Terminal procedure: sacrifice by CO inhalation, flash freezing, pulverized in a blender and an aliquot of the powder was extraxted and analyzed for its CTC content by GC with an electron capture detector (ECD)
- Analysis of organs: no, the whole carcass was flash frozen, grinded and an aliqout of the powder and extracted with n-hexane (1.5 g of powder, vigorously shaken for 5 min in 15 mL n-hexane


SAMPLE PREPARATION
- Storage procedure: no storage, samples were directly analyzed
- Preparation details: 5 µL of the powder extracts or an unspecified aliquot of the air extraction samples were directly allpied to GC analysis


ANALYSIS
- Method type(s) for identification: GC-ECD (electron capture detector ), Perkin-Elmer model 900 with an electron capture detector (63Ni foil). The column used was 118-in. by 3-ft. stainless and contained Porapak Q, 60 to 80 mesh. Column temperature was 130- 190°C
- Liquid scintillation counting results (cpm) converted to dpm as follows: not applicable
- Validation of analytical procedure: not reported
- Limits of detection and quantification: not reported


OTHER: substance recovery: 80 - 100 %

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

- Expired air (if applicable): 52.1 ± 21.2 µg
- Complete body: 309 ± 54.7 µg

Total recovery:

- Total recovery: reported to be 80 - 100 %

Percutaneous absorption

Dose:

0.792 g/30 -35 g bw

Parameter:

percentage

Absorption:

0 %

Remarks on result:

other: 15 min

Remarks:

0.04558 % absorbed in 15 min, 53.6 ± 9.30 nmol/min/cm² skin

Any other information on results incl. tables

- Non-occlusive cover + enclosure rinse: not analyzed

- Skin wash: not analyzed

- Skin test site: not analyzed

- Skin, untreated site: not analyzed

- Blood: not analyzed

- Carcass: not analyzed

- Urine: not analyzed

- Cage wash + cage wipe: not analyzed

- Faeces: not analyzed

- Expired air (if applicable): 52.1 ± 21.2 µg

- Serial non-detects in excreta at termination: not analyzed

- Receptor fluid, receptor chamber, donor chamber (in vitro test system): not applicable

- Skin preparation (in vitro test system): not applicable

- Stratum corneum (in vitro test system): not applicable

- complete body: 309 ± 54.7 µg

- Total recovery: reported to be 80 - 100 % - Recovery of applied dose acceptable: no data - Results adjusted for incomplete recovery of the applied dose: no data - Limit of detection (LOD): no data - Quantification of values below LOD or LOQ: no data

Applicant's summary and conclusion

Conclusions:

The present study (Tsuruta 1975) describes the percutaneous absorption of CTC in ICR mice after single application of 0.5 mL (0.792 g) CTC to the shaved skin. No official guideline was followed but the results should be comparable to short term results from OECD TG 427.

Executive summary:

The potential of CTC to penetrate the skin and be absorped via this route was tested by application of 0.5 mL (= 0.792) of the test item for 15 min in an occlusive reservoir glued to the shaved skin of male ICR mice. During exposure exhaled CTC was trapped in washing flasks. At the end of exposure the reservoir was withdrawn, animals were sacrificed by CO inhalation, flash frozen, pulverized in a blender and an aliquot of the powder was extracted and analyzed for its CTC content by GC with an electron capture detector (ECD). Recovery of CTC was reported to be between 80 and 100 % but the basis for the calculation was not detailed. As CTC is still liquid at a temperature of -20 °C it remains unclear whether CTC might have been lost during the grinding procedure. The determined absorption rate was 0.04558 % absorbed in 15 min, or 53.6 ± 9.30 nmol/min/cm² skin. Due to the reasons stated above this might be an underestimation of the actual absorption rate.