Tetrachloroethylene

Dermal absorption

Administrative data

Endpoint:

dermal absorption

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Studies based on which the toxicokinetic behaviour of the substance can be derived, considered acceptable for assessment. Also peer-reviewed under Regulation 793/93.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

other: European Union Risk Assessment Report (EU-RAR 2008)

Title:

European Union Risk Assessment Report: Tetrachloroethylene, CAS No 127-18-4, EINECS No 204-825-9. Final draft human health report for publication

Author:

Rapporteur: United Kingdom, on behalf of the European Union

Year:

2008

Materials and methods

Principles of method if other than guideline:

no information available

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Tetrachloroethylene

EC Number:

204-825-9

EC Name:

Tetrachloroethylene

Cas Number:

127-18-4

Molecular formula:

C2Cl4

IUPAC Name:

tetrachloroethene

Details on test material:

no information available

Radiolabelling:

yes

Remarks:

in one study with female hairless guinea pigs

Test animals

Species:

other: mice, rats and guinea pigs

Strain:

other: nude mice, F344 rats, guinea pigs

Sex:

male/female

Details on test animals or test system and environmental conditions:

no information available

Administration / exposure

Type of coverage:

other: ranged from occuluded to open

Vehicle:

other: undiluted and aqueous solutions

Duration of exposure:

In vivo exposures ranged from 70 minutes to a maximum of 24 hours and in vitro exposure ranged between 2-6 hours

Doses:

ranged from diilute aqueous solutions (20-100 ppb) to undiluted (2ml)

No. of animals per group:

limited information available

Details on study design:

limited information available

Details on in vitro test system (if applicable):

Tsuruta (1977) measured the penetration of tetrachloroethylene in vitro across excised rat skin held in a diffusion cell. Tetrachloroethylene (1 ml) was applied to about 4 cm2of the skin for 2 - 6 hours and its penetration into a saline solution was determined by gas chromatography. The lag time needed to establish steady-state diffusion was found to be 2.5 hours and the mean penetration rate was 0.55 nmol/min/cm2, 44 times smaller than the rate derived from the in vivo study in mice. In comparison, the mean rate measured in vitro for 1,2-dichloroethane was 169 nmol/min/cm2 and the time to reach a steady-state was about 0.5 hours. References Tsuruta H (1977): Percutaneous absorption of organic solvents. 2) A method for measuring the penetration rate of chlorinated solvents through excised rat skin, Ind Health. 15; 131-139.

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

limited information available

Total recovery:

limited information available

Conversion factor human vs. animal skin:

limited information available

Any other information on results incl. tables

The dermal absorption of liquid tetrachloroethylene (both undiluted and in aqueous solution) and of tetrachloroethylene vapour have been investigated in several animal species. In one study, 5 anaesthetised guinea pigs with indwelling arterial cannulas had undiluted tetrachloroethylene (1 ml) added to a sealed skin depot on shaved skin (Jakobsonet al, 1982). Serial blood samples were collected at least every 30 minutes during a 6-hour exposure. Blood tetrachloroethylene concentrations, measured by gas chromatography, peaked at about 1.5 µg/ml at 30 minutes then gradually fell, despite the continuing exposure, to 0.6 µg/ml at 6 hours.

In a study using a similar exposure method, 3 anaesthetised mice had 0.5 ml tetrachloroethylene applied to depots on shaved abdominal skin for 15 minutes (Tsuruta, 1975). The mean amounts of tetrachloroethylene retained in the whole body (173 µg) and expired in the breath (4 µg) were determined by gas chromatography, and added to give the total amount of tetrachloroethylene absorbed percutaneously. The mean percutaneous absorption rate was calculated to be 24 nmol/min/cm². In comparison, the mean rates for tetrachloroethane and 1,2-dichloroethane were 62 and 479 nmol/min/cm²respectively.

 

The dermal absorption of undiluted and aqueous solutions of tetrachloroethylene were investigated by adding them to glass exposure cells on the dorsal skin of male F344 rats (Morganet al, 1991). The cells contained 2 ml of fluid, covered a skin area of 3 cm²and were left on for 24 hours. Blood samples were obtained via indwelling venous catheters at 0, 0.5, 1, 2, 4, 8, 12 and 24 hours of exposure. The peak tetrachloroethylene blood level obtained with undiluted tetrachloroethylene was about 21 µg/ml and was reached at the first time-point after the start of the exposure, 0.5 hours. When saturated (102 µg tetrachloroethylene/ml), 67% saturated and 33% saturated aqueous solutions were used, the tetrachloroethylene concentrations in blood were near the lower detection limits of the analytical method (gas chromatography) used, and too variable to be informative.

 

In another study assessing dermal uptake of tetrachloroethylene from aqueous solution, anaesthetised female hairless guinea pigs were immersed up to their shoulders in very dilute (20 - 100 ppb) solutions of¹⁴C-labelled tetrachloroethylene in an airtight chamber containing no headspace (Bogenet al, 1992). Dermal absorption was estimated by comparing the loss of radiolabel from chamber water in experiments with and without the guinea pigs. Radiolabel recovered in urine and faeces after the 70-minute exposures was also measured at intervals over the following 2 - 4 weeks. The mean permeability constant derived from an experiment using 5 animals was 0.37 ml/cm².hour.  In comparison, values of 0.23 and 0.13 were obtained for trichloroethylene and chloroform respectively. For tetrachloroethylene, a mean value of about 14% of the estimated dermal uptake was excreted in urine or faeces and the mean time to excrete 95% of the metabolised dose was 6 days.

 

Finally, in a study designed to examine dermal uptake of tetrachloroethylene from the vapour phase, male nude mice, each attached by tracheal cannula to a respirator, were exposed in a chamber to 200, 1000 or 3000 ppm (1380, 6900 or 20700 mg/m³) tetrachloroethylene for 2, 4 or 6 hours (Tsuruta, 1989). At the end of the exposure period the amount of tetrachloroethylene retained in a homogenate of the whole body was determined by gas chromatography. It was found that tetrachloroethylene vapour was absorbed rapidly across the skin and was detected in the body at all exposure concentrations. The amount of skin absorption increased linearly with exposure time and the skin absorption rate at the steady state was proportional to the exposure concentration. 

 

References

 

Bogen KT, Colston BW Jr and Machicao LK (1992): Dermal absorption of dilute aqueous chloroform, trichloroethylene and tetrachloroethylene in hairless guinea pigs,Fund Appl Toxicol.18; 30-39.

 

Jakobson I, Wahlberg JE, Holmberg B and Johansson G (1982): Uptake via the blood and elimination of 10 organic solvents following epicutaneous exposure of anaesthetised guinea pigs,Toxicol Appl Pharmacol.63; 181-187.

 

Morgan DL, Cooper SW, Carlock DLet al(1991): Dermal absorption of neat and aqueous volatile organic chemicals in the Fischer 344 rat,Environ Res.55; 51-63.

 

Tsuruta H (1975): Percutaneous absorption of organic solvents. 1) Comparitive study of in vivo percutaneous absorption of chlorinated solvents in mice,IndHealth.13; 227-236.

 

Tsuruta H (1989): Skin absorption of organic solvent vapors in nude mice in vivo,Ind Health.27; 37-47.

Applicant's summary and conclusion

Conclusions:

Based on the findings of the various studies, there is no bioaccumulation potential for tetrachloroethylene.

Executive summary:

A number of studies were conducted in various species ranging from mice, rats and guinea pigs to evaluate the bioaccumulation potential of tetrachloroethylene (varying concentrations for aqueous solutions and undiluted) via dermal exposure. The findings revealed that the rate of skin penetration appeared to be markedly lower than for other solvents, with both the experimental data and the physico-chemical properties of tetrachloroethylene indicating that a worst-case absorption value of 50% is appropriate for risk assessment purposes. Although a study in animals suggested substantial dermal absorption of tetrachloroethylene vapour, human evidence indicates that dermal absorption of vapour would only contribute a minimal (~0.3-1%) amount of that which would be absorbed by inhalation under normal conditions. Following absorption tetrachloroethylene is subject to widespread systemic distribution to all organs and tissues with selective partitioning into fat. Hence based on the findings of these various studies, there is no bioaccumulation potential for tetrachloroethylene.