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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study report with acceptable restrictions (no data on analytical purity of unlabelled test substance, non-GLP, limited documentation of methods and results)
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Principles of method if other than guideline:
An in vivo percutaneous absorption study was carried out with the substance using both control rats and rats treated topically with 2000 mg/kg bw/day for thirteen weeks. The percutaneous absorption of the substance in rats was measured over 4 days following a single topical administration of 14C-labelled test substance (2000 mg/kg bw).
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(tridecyl) adipate
EC Number:
241-029-0
EC Name:
Bis(tridecyl) adipate
Cas Number:
16958-92-2
Molecular formula:
C32H62O4
IUPAC Name:
ditridecyl adipate
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Details on the strain: Rat/crl COBS CD[SD] BR/Charles River, Lakeview, New Jersey
- Source: Charles River, Lakeview, New Jersey
- Age at study initiation: 49 days
- Weight at study initiation: males: 161.9 - 166.8 g; females: 149.2 - 150.5 g
- Housing: individually, in suspended, stainless steel cages, with wire mesh bottoms and fronts
- Diet: Purina Certified Lab Chow #5002 in pellet form, ad libitum
- Water: tap water, delivered by an automatic watering system, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
1. Pretreated rats: 13 weeks topical exposure (unlabelled test substance)
Treatment: 4 days (14C-labelled test substance)
2. Untreated rats: control rats from 13-week dermal study
Treatment: 4 days (14C-labelled test substance)
Doses:
2000 mg/kg bw
No. of animals per group:
5 animals/sex/dose
Control animals:
no
Details on study design:
APPLICATION OF DOSE:
A plastic ring with an inside area of 1.2 cm2 was attached securely to the back of each rat with adhesives. A single dose of the test substance was applied to completely cover the skin inside the ring (58 µL). The amount of test substance used was equivalent to the high dose used in the thirteen week study (on a µg/cm2 skin surface basis).

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes
To prevent the rats from removing the test substance, a wire mesh cover was attached to the ring. Each rat was fitted with a carboard "Elizabethan" collar and placed in a separate metabolism cage for once-daily collection of urine and feces.

SAMPLE COLLECTION
- Collection of urine and faeces: once daily
- Terminal procedure: blood, tissues and organs were removed from the rats after sacrifice for determination of levels of radioactivity, as measured by liquid scintillation counting.
- Analysis of organs: liver, kidney. stomach, bladder, small intestine, and large intestine


Results and discussion

Percutaneous absorptionopen allclose all
Key result
Dose:
2000 mg/kg bw
Parameter:
percentage
Absorption:
10.6 - 11.6 %
Remarks on result:
other: 4 days
Remarks:
rats previously untreated
Key result
Dose:
2000 mg/kg bw
Parameter:
percentage
Absorption:
9.1 - 10.8 %
Remarks on result:
other: 4 days
Remarks:
rats pre-treated for 13 weeks at 2000 mg/kg bw/day with the test substance

Any other information on results incl. tables

Table 1: Percentage of the applied 14C-labelled test substance recovered in the body

 

 

Male

Female

Control rats

11.6% (SD = 3.2)

10.6% (SD = 5.3)

Pre-treated rats

10.8% (SD = 1.6)

9.1% (SD = 0.6)

No significant differences were observed in comparing the percutaneous absorption of the test substance in male and female rats. Furthermore, no significant differences were observed in comparing the percutaneous absorption of the substance in control and pretreated rats. Thus, it appears that repeated treatment of the skin with the test substance at 2000 mg/kg bw/day for thirteen weeks had no effect on the percutaneous absorption of the substance in male and female rats.

 

The absorbed substance was observed to eliminate very slowly from the animals following diffusion through the stratum corneum. After four days, 52-63% of the substance absorbed by control rats and 81-87% absorbed by treated rats was still retained in the body. These results suggest that thirteen weeks of dermal treatment with the substance had an effect on the elimination of absorbed test substance from the animals.

Table 2: In vivo percutaneous absorption of 14C-labelled test substance (2000 mg/kg bw) in control rats

 

 

 

Summed & applied dose recovered (mean & SD of 4 rats)

Sex

Days

Urine

Faeces

Tissues

Total

Male

1

0.19 (0.21)

0.02 (0.01)

-

0.21 (0.22)

2

0.87 (0.75)

0.08 (0.12)

-

0.95 (0.82)

3

2.68 (1.65)

0.36 (0.31)

-

3.04 (1.88)

4

3.52 (1.76)

0.70 (0.25)

7.35 (1.50)

11.57 (3.18)

Female

1

0.04 (0.07)

0.04 (0.04)

-

0.08 (0.12)

2

0.31 (0.47)

0.08 (0.08)

-

0.39 (0.55)

3

3.75 (4.21)

0.25 (0.24)

-

4.00 (4.14)

4

4.73 (4.61)

0.42 (0.23)

5.49 (1.00)

10.64 (5.33)

 

 

Table 3: In vivo percutaneous absorption of 14C-labelled test substance (2000 mg/kg bw) in pre-treated rats

 

 

 

Summed & applied dose recovered (mean & SD of 4 rats)

Sex

Days

Urine

Faeces

Tissues

Total

Male

1

0.05 (0.07)

0.06 (0.03)

-

0.11 (0.08)

2

0.27 (0.22)

0.14 (0.07)

-

0.41 (0.25)

3

0.56 (0.40)

0.37 (0.16)

-

0.92 (0.42)

4

0.73 (0.43)

0.64 (0.27)

9.42 (1.64)

10.79 (1.56)

Female

1

0.13 (0.13)

0.06 (0.03)

-

0.18 (0.13)

2

0.70 (0.68)

0.14 (0.07)

-

0.85 (0.73)

3

1.02 (0.86)

0.26 (0.13)

-

1.28 (0.98)

4

1.34 (0.90)

0.35 (0.15)

7.43 (1.29)

9.13 (0.55)

 

Applicant's summary and conclusion