[No public or meaningful name is available]

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

not reported; tables and plots dated 1984-04-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no GLP study, but the test parameters documented are sufficient to accept the data (Klimisch et al., 1997)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

Version / remarks:

(few similarities)

Deviations:

yes

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 417 (Toxicokinetic)

Deviations:

yes

Principles of method if other than guideline:

No sufficient information about test substance, experimental animals, their housing and feeding conditions. One dose level of test substance was administered. No data on type of coverage of the applied area. No interpretation of results.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diallyl 2,2'-oxydiethyl dicarbonate

EC Number:

205-528-7

EC Name:

Diallyl 2,2'-oxydiethyl dicarbonate

Cas Number:

142-22-3

Molecular formula:

C12H18O7

IUPAC Name:

diallyl 2,2'-oxydiethyl dicarbonate

Details on test material:

- Name of test material (as cited in study report): Carbon-14 labelled diallyl-diglycol carbonate (CR-39)
- Substance type: data not available
- Physical state: data not available
- Analytical purity: data not available
- Impurities (identity and concentrations): data not available
- Composition of test material, percentage of components: data not available
- Isomers composition: data not available
- Purity test date: data not available
- Lot/batch No.: 1222-145, assay number 81-221797
- Expiration date of the lot/batch: data not available
- Radiochemical purity (if radiolabelling): 1.29 microcuries
- Specific activity (if radiolabelling): data not available
- Locations of the label (if radiolabelling): (allyl-14C1) moiety of diallyl-diglycol carbonate
- Expiration date of radiochemical substance (if radiolabelling): data not available
- Stability under test conditions: data not available
- Storage condition of test material: data not available

- Other: The 14C labeled CR-39 utilized in this study was synthesized by New England Nuclear and was provided by the sponsor. A precipitant formed when the material was dissolved in absolute EtOH. The EtOH soluble fraction was assayed by thin layer chromatography using Silica Gel G. and a hexane:ether (40:60 , v/v) solvent system. The EtOH soluble fraction had the same rf value as a CR-39 reference standard. Only the EtOH soluble fraction was used in these studies.

Radiolabelling:

yes

Remarks:

C14

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Administration / exposure

Type of coverage:

not specified

Vehicle:

ethanol

Duration of exposure:

5 days

Doses:

- Nominal doses: 1.29 microcuries of C14 labeled CR-39
- Actual doses: no data
- Actual doses calculated as follows: no data
- Dose volume: 100 µL
- Rationale for dose selection: not reported

No. of animals per group:

3

Control animals:

no

Results and discussion

Percutaneous absorption

Parameter:

percentage

Absorption:

0 %

Remarks on result:

other: 5 th day

Remarks:

excretion rates via urine and absorption % with and without washing were determined

Conversion factor human vs. animal skin:

not applicable

Any other information on results incl. tables

Remarks on tables and enclosed plots (see "Attached background material"):

Appendix 1 lists the parameters used in the subsequent data analysis.

Table number 1 lists the dpm values, the total volume of urine collected, and the calculated % dose excreted during each collection t ime interval for each subject. For example, under 0-6 hours for subject 1, 985.7 and 1013.3 are the calculated dpm values, 84 is the volume of urine collected in milliliters and 2.964 is the calculated % 14C dose excreted into the urine.

Table number 2 lists the % dose excreted into the urine and removed by the 24 hour washing procedure. The % dose excreted into the urine of CR-39 was determined to be 17.6% (standard deviation of 1.8). The maximum rate of excretion was observed during the first 24 hours. The 24 hour washing procedure removed 9.0% (standard deviation of 4.7) of the applied dose.

No 14C was detected in the feces, site of application or in the carcass of the animals.

Finally two graphs are enclosed. The first is a linear plot of the average % dose excreted into the urine per hour versus time at the midpoint of the collection period. The second is a semilog plot of the % dose excreted into the urine per hour versus time at the midpoint of the collection period.

 

Applicant's summary and conclusion

Conclusions:

The excretion rates were the highest within the first 24 hours. Percutaneous penetration of test substance is high.
17.6% of the applied dose were excreted into the urine during 5 days. The 24 hour washing procedure removed 9% (standard deviation) of the applied dose. No 14C was detected in the feces, site of application or in the carcass of animals.

Executive summary:

Carbon-14 labeled diallyl-diglycol carbonate (CR-39) was applied to the postauricular skin of the guinea pigs. Percutaneous absorption of the CR-39 was determined by measurement of the total amount of 14C label excreted into the urine.

The urine samples were collected every six hours the first day then daily for 5 days and assayed by liquid scintillation method. The skin of the animals was washed after 24 hours of application. The site of application and the remaining carcass were tested for C14 label.

17.6% of the applied dose were excreted into the urine during 5 days. The 24 hour washing procedure removed 9% (standard deviation) of the applied dose. No 14C was detected in the feces, site of application or in the carcass of animals.

Since the multi-constituent to be registered (EC 700-483-4) contains as main ingredient 'diallyl 2,2'oxydiethyl dicarbonate', the experimental data from this substance were used in a read-across approach.