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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP study, but performed equivalent to guideline with internal review. Well documented study
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
not applicable
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
1,2-dichloroethane
Radiolabelling:
no

Test animals

Species:
other: human and rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not applicable

Administration / exposure

Type of coverage:
other: unoccluded (neat material) and occluded (aqueous solutions)
Vehicle:
other: neat material or aqueous solution
Duration of exposure:
up to 8 hours
Doses:
5, 10, 25 and 100 µL/cm² as neat material and as 1000 µg/mL solution in water (200 µL/cm²)
No. of animals per group:
not applicable
Control animals:
no
Details on study design:
not applicable
Details on in vitro test system (if applicable):
Human and rat epidermal membranes were prepared from whole skin and mounted in glass diffusion cells. The integrity of the membranes was determined by measurement of their permeability to tritiated water. Samples with a permeability coefficient > 1.5 (exp-3) cm/h (human) or > 2.5 (exp-3) cm/h (rat) were deemed to have been damaged during preparation and were discarded. The remaining intact samples were used for the assessment of 1,2-dichloroethane absorption.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Total recovery:
not indicated
Percutaneous absorptionopen allclose all
Dose:
5 µL/cm² (neat)
Parameter:
percentage
Absorption:
91.9 - 398 %
Remarks on result:
other: 0.25 hour
Remarks:
mean absorption rate in µg/cm²/hr (not %); first value: human; second value: rat
Dose:
10 µL/cm² (neat)
Parameter:
percentage
Absorption:
81.9 - 873 %
Remarks on result:
other: 0.25 hour
Remarks:
mean absorption rate in µg/cm²/hr (not %) ; first value: human; second value: rat
Dose:
25 µL/cm² (neat)
Parameter:
percentage
Absorption:
104 - 1 780 %
Remarks on result:
other: 0.25 hour
Remarks:
mean absorption rate in µg/cm²/hr (not %); first value: human; second value: rat
Dose:
100 µL/cm² (neat)
Parameter:
percentage
Absorption:
106 - 6 810 %
Remarks on result:
other: 0.25 hour
Remarks:
mean absorption rate in µg/cm²/hr (not %); first value: human; second value: rat
Dose:
200 µL/cm² (in water)
Parameter:
percentage
Absorption:
25.8 - 78.4 %
Remarks on result:
other: 0.25 hour
Remarks:
mean absorption rate in µg/cm²/hr (not %); first value: human; second value: rat
Dose:
100 µL/cm² (neat)
Parameter:
percentage
Absorption:
205 %
Remarks on result:
other: 1.0 hour
Remarks:
mean absorption rate in µg/cm²/hr (not %); first value: human; no second value
Dose:
200 µL/cm² (in water)
Parameter:
percentage
Absorption:
20.3 - 33.1 %
Remarks on result:
other: 1.0 hour
Remarks:
mean absorption rate in µg/cm²/hr (not %); first value: human; second value: rat
Conversion factor human vs. animal skin:
The difference between absorption through human as compared to rat skin varied between 1:3 to approx. 1:65 during the first 15 minutes.

Any other information on results incl. tables

For all applications, 1,2-dichloroethane absorption was faster through rat epidermis than through human epidermis by factors varying from about 3 to 65 times, depending on the application.

The 1000 μg/mL occluded aqueous applications were made under conditions which provided an infinite dose and avoided losses of 1,2-dichloroethane by evaporation, thus enabling the direct comparison of 1,2-dichloroethane absorption through human and rat epidermis with the absorption of other chemicals which have been assessed under similar conditions (Dugard and Scott, 1984). The absorption of 1,2-dichloroethane through epidermal membranes from both species was fastest during the very early period of exposure and had virtually ceased by 1 hour after application. The reduction in absorption rate occurred in both species when the amount of 1,2-dichloroethane absorbed had reached 20-25 μg/cm² (i.e. approximately 10 % of the amount applied), however, this value was reached earlier with rat epidermis (0.25 hour) than with human epidermis (1 hour). The rate of 1,2-dichloroethane absorption from this application during the first 0.25 hour was only 3 times faster through rat epidermis (absorption rate = 78.4 μg/cm²/hr permeability coefficient (Kp) = 0.078 cm/hr) than through human epidermis (absorption rate = 25.8 μg/cm²/hr; Kp = 0.026 cm/hr). These rates were considered to indicate that, intrinsically, rat and human epidermis have a similar permeability to 1,2-dichloroethane.

For all the neat unoccluded applications, except the 100 μL/cm² application to human epidermis, the applied 1,2-dichloroethane had evaporated from the skin surface before the time of the first sample (0.25 hour after addition). The 100 μL/cm² application to human epidermis was the only neat application to display an increased 1,2-dichloroethane absorption rate after 0.25 hour (106-205 μg/cm²/hr). Although the applied 1,2-dichloroethane evaporated faster from the rat epidermis, possibly due to the increased surface area afforded by the fur "stubble", the 1,2-dichloroethane absorption rate during the first 0.25 hour increased almost proportionately with increasing amounts applied. Absorption had virtually ceased by 0.25 hour for all applications.

Absorption of neat 1,2-dichloroethane through human epidermis during the first 0.25 hour of exposure was similar for all applications (82-106 μg/cm²/hr); thus, increasing the dose did not affect the absorption rate. The rate of absorption at later times did not decrease as rapidly as was seen with rat epidermis, but continued until approximately 1 hour after application. The difference between absorption through rat and human epidermis from the 5 μL/cm² application (4-1) was similar to the difference measured from the aqueous application (3-1). For the other neat applications the factors of difference were greater, varying between 10 and 65 times, dependent on the volume applied.

Applicant's summary and conclusion

Conclusions:
Consideration of these results and observations suggested that neat 1,2-dichloroethane formed a reservoir in human epidermis, allowing fairly rapid absorption to continue for a very short time after the applied 1,2-dichloroethane has evaporated. With rat epidermis, however, little or no such reservoir was built up and absorption rapidly decreased after the application evaporated.
Executive summary:

Human and rat epidermal membranes were prepared from whole skin samples and mounted in glass diffusion cells in order to assess in vitro absorption rates of 1,2 dichloroethane. Neat applications (5, 10, 25 and 100 µL/cm²) were left uncovered after application, while the aqueous application (200 µL/cm²) was occluded throughout the entire exposure period. The data obtained from the applications of the aqueous 1,2 -dichloroethane solution showed that intrinsic permeability of human and rat epidermis to 1,2-dichloroethane was similar. From the neat material, 1,2 -dichloroethane absorption through human epidermis was consistently over-estimated by rat epidermis. The absorption of 1,2-dichloroethane from the neat material through rat epidermis was dependent upon the dose applied. 1,2 -dichloroethane absorption through human epidermis was not affected by varying the applied dose of neat material. The data obtained in this study indicated that 1,2 -dichloroethane absorption through human and rat epidermis was relatively fast.