D-Glucitol, 1-deoxy-1-(methylamino)-, N-[C8-16 (even numbered) and C18 unsaturated acyl] derivs.

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study according to GLP. Limitations due to low number of evaluated animals (n=2), but overall result plausible based on all available data.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.7600 (Dermal Penetration)

Deviations:

yes

Remarks:

(limited animal number (n=2)).

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Glucamide 24

IUPAC Name:

Glucamide 24

Constituent 2

Reference substance name:

287735-50-6

Cas Number:

287735-50-6

IUPAC Name:

287735-50-6

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): N-Lauroyl [14C]-glucose amide (C12-GS-Base)
- Physical state: white solid
- Radiochemical purity (if radiolabelling): 99.1%
- Specific activity (if radiolabelling): 19 mCi/g
- Storage condition of test material: room temperature

Radiolabelling:

yes

Remarks:

(14C)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Weight at study initiation: 175 - 225 g
- Fasting period before study: overnight before dosing
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 4 days

Administration / exposure

Type of coverage:

open

Vehicle:

other: absolute ethanol:water (80:20)

Duration of exposure:

single dermal application for 72 hours

Doses:

9.9 mg/kg body weight (0.26 mg/cm2)

No. of animals per group:

Initially 4 males; 2 animals accidentally ingested residual test material from exposed test site were removed from evaluation

Control animals:

no

Details on study design:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Urine, faeces, CO2, blood, plasma, tissues, cage washes, GI tract wash. Tissue collected were liver (entire), kidneys, testes or (Ovaries and uterus), heart, lung (entire), spleen, pancreas, brain, bone marrow, muscle (Hind limb; right), bone (femur; both), adipose (at the psoas), Gl tract, Carcass, skin (test site) and skin (adjacent).
- Time and frequency of sampling: Urine and feces were collected at 24, 48 and 72 hours after treatment. CO2 was collected from the rats at 24, 48 and 72 hours. CO2 safety trap (one/rat) was collected at the end of the 72 hour test period. At the end of the 24-, 48- and 72-hour collection period, cages were washed with 3A alcohol followed by distilled water. These cage washes were submitted separately to Radiochemistry for analysis. Tissue samples were collected after sacrifice of animals.
- Blood sampling and sacrifice: At the end of the 72 hour test period, rats were sacrificed with an overdose of carbon dioxide. Blood was collected from the inferior vena cava in a heparinized syringe. A portion of this sample was submitted to Radiochemistry as ‘blood’. The plasma fraction from the remainder of the blood was prepared by centrifugation. This sample was submitted to Radiochemistry as ‘plasma’.

Results and discussion

Signs and symptoms of toxicity:

no effects

Dermal irritation:

not specified

Percutaneous absorption

Dose:

0.26 mg/cm2

Parameter:

percentage

Absorption:

< 1 %

Remarks on result:

other: 72 hours

Any other information on results incl. tables

Total Recovery: Recovery was 95 ± 5% (Mean ± S.E., n=2)

Applicant's summary and conclusion

Conclusions:

The extent of radioactivity absorption following dermal administration of n-Lauryl [14C(U)]-glucose amide ([14C]-C12-GS-Base) at 9.9 mg/kg bw (0.26 mg/cm2) to rat was estimated to be <1% over 72-h test period. A very low amount of residual radioactivity was detected in all tissues and the principle route of elimination was urine.

Executive summary:

The absorption, distribution and excretion of n-Lauryl [14C(U)]-glucose amide ([14C]-C12-GS-Base) after dermal administration was determined by following the methods similar to the OECD guideline 417 (Toxicokinetics).

Male Sprague Dawley rats (from Charles River) were used in study. One group (number of animals= 2) of rats was used in the study to determine absorption, distribution and excretion (ADE) of test substance. Animals were housed in metabolism cages during the study period.

Test formulation (19.3 mg/g solution) was prepared in absolute ethanol. Animals were treated once with dose of 9.9 mg/kg bw (0.26 mg/cm2). Approximately 0.1 mL of test solution was applied within a glass ring glued on the hair clipped backs of animals, with the help of a syringe. The radioactive dose administered to animals was approximately 9 µCi/animal.

Animals were sacrificed by an overdose of CO2 after 72 hours of treatment. Urine and faeces were collected at 24, 48 and 72 h time intervals after treatment. Tissue samples were collected after sacrifice of the animals.

The extent of absorption following dermal administration of the radio-labeled test substance at 9. 9 mg/kg bw (0.26 mg/cm2) was estimated to be < 1% over a 72-hour test period.

Inspection of individual tissue radioactivity distribution at 72 hours showed the presence of very low levels of residual radioactivity in all tissues. The femur contained the highest radioactive content [20 times background (plasma radioactive content)] followed by carcass, whole blood, adipose and bone marrow. AII other tissues were five times background or less.

At the end of the 72-hour test period, 94.4% of the dosed radioactivity was recovered in the test site skin plus dose cell wash, 0.27% in the urine plus cage wash, 0.19% in the tissues plus carcass, 0.1% in the feces plus Gl tract wash and 0.02% in the expired carbon dioxide.Theprincipal route of radioactivity elimination was urine.

The % total recovery of test substance was 95±5% after treatment.

In conclusion, the extent of radioactivity absorption following dermal administration of n-Lauryl [14C(U)]-glucose amide ([14C]-C12-GS-Base) at 9.9 mg/kg bw (0.26 mg/cm2) to rat was estimated to be <1% over 72-h test period. A low amount of residual radioactivity was detected in all tissues and the principle route of elimination was urine.