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Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
no information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not according to GLP nor to specific test guideline. Usefull as preliminary indication.
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Percutaneous absorption of cadmium in rabbit and hairless mouse
Author:
Kimura M & Otaki N
Year:
1972
Bibliographic source:
Ind. Health. 10: 7-10

Materials and methods

Principles of method if other than guideline:
Study was conducted to assess the percutaneous absorption of Cd.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CdCl2
Radiolabelling:
no

Test animals

Species:
other: rabbit and mouse
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
Male rabbits with the average weight of 3-4 kg were used. Male hairless mice with the average weight of 25 g were used.

Administration / exposure

Type of coverage:
open
Vehicle:
not specified
Duration of exposure:
rabbits: 5 wk ; mice: 2 wk
Doses:
1% solution of CdCl2 or a 2% w/w ointment
No. of animals per group:
no information
Control animals:
yes
Details on study design:
APPLICATION OF DOSE:
Rabbit: The hair of the back of rabbit was removed (exposure area; 10 sq cm). The aqueous solution of CdCl2 (1mL = 10 mg of CdCl2 = 6.1mg of Cd) was applied on the skin of rabbit for five times in three weeks. The ointment of CdCl2 (1g = 20 mg of CdCl2 = 12.2 mg of Cd) was placed on the back skin of rabbit for five times in three weeks. The rabbit treated with the cadmium was killed after two weeks.
Mouse: On the other hand, the ointment of CdCl2 (50mg = 1mg of CdCl2 = 0.61mg of Cd) was applied on the back skin of hairless mouse, which followed to be killed after one week. The other mouse was given the ointment for five times in a week, and followed to be killed after one week.

SAMPLE COLLECTION
- Analysis of organs: The amounts of cadmium in the organs were determined by the atomic absorption spectrometer, Hitachi model 207, after the ashing
Details on in vitro test system (if applicable):
not appicable

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
no information
Total recovery:
no information
Percutaneous absorptionopen allclose all
Dose:
1% solution CdCl2 (6.1mg Cd/ml)
Parameter:
percentage
Absorption:
ca. 0.4 %
Remarks on result:
other: 5 weeks
Remarks:
1% solution CdCl2 (6.1mg Cd/ml); rabbits; in liver and kidney
Dose:
2% ointment of CdCl2 (12.2mg Cd/ml)
Parameter:
percentage
Absorption:
>= 0.4 - <= 0.6 %
Remarks on result:
other: 5 weeks
Remarks:
2% ointment of CdCl2 (12.2mg Cd/ml); rabbits; in liver and kidney
Dose:
2% ointment of CdCl2 (0.61 mg Cd/ml)
Parameter:
percentage
Absorption:
>= 0.2 - <= 0.8 %
Remarks on result:
other: 2 weeks
Remarks:
2% ointment of CdCl2 (0.61 mg Cd/ml); mice; in liver and kidney
Conversion factor human vs. animal skin:
no information

Any other information on results incl. tables

percutaneous absorption and accumulation in the liver and in the kidney:

rabbits: 0.4 -0.6%

mice: 0.2 -0.8%

After the treatments with the cadmium, the organs of rabbits and hairlessmice were analyzed. The amounts of the cadmium in the liver and kidney are given below.

Cadmium content in liver and kidney of rabbit given cadmium percutaneously.

 

Rabbit

Kidney

r/g     Totalr

Liver

r/g     Totalr

Cdfoundr

Cd*1absorbedr

% for applied cadmium

Control

1.14

24.5

0.09      9.6

   34.1

 

 

W*2

2.95

69

0.83       86

155

121

    0.40

A*3

B*4

8.62

9.42

148

212

1.65    59

2.12   250

307

406

273

372

0.45      

0.61

*1  Cd found - Control (Cd found)

*2  Given 1 ml of the CdC!2aqueous solution for 5 times in 3 weeks and killed

     after 2weeks.  Total Cd = 30.5mg

*3  Given 1 g of the. CdCl2 ointment A for 5 times in 3 weeks and killed after

     2 weeks.Total Cd = 61mg

*4  Given 1 g of the CdCl2ointment B for 5 times in 3 weeks and killed after 

      2  weeks.Total Cd=61mg

Cadmium content in liver and kidney of hairless mouse givencadmium percutaneously.

 

Hairless mouse

Kidney

r/g     Totalr

Liver

r/g     Totalr

r

Cd             Cd*1

Found      absorbed

r                r

%forappliedcadmium

Control

0.26

0.11

0.10

0.11

0.22

 

 

"

0.26

0. 11

0.06

0.10

0.21

 

 

A*21

0.55

0. 32

0.79

1.57

1.87

1.67

0.27

2

0.34

0.22

0.24

0.43

0.65

0.43

0.07

3

0.39

0.22

0.49

0.98

1.20

0.98

0.16

B*21

0.29

0.21

0.39

0.71

0.92

0.70

0.11

2

0.50

0.28

0.62

0.97

1.25

1.23

0.20

3

0.52

0.33

0.66

1.36

1.69

1.47

0.24

A*2 4

4.99

3.09

12.79

18.03

21.12

20.90

0.85

5

4.96

2.67

13.21

18.76

21.43

21.21

0.87

B*2  4

4.03

2.30

8.88

12.25

14. 55

14.33

0.59

5

4.22

2.53

12.44

18.04

20.57

20.35

0.83

*1  Cd found - Control (Cd found)

*2  A: Cream-like ointment (2%CdCl2w/w).   B; Milk-like ointment (2% CdCl2 w/w).

Mice 1, 2 and 3 were given 50 mg of ointment (1 mg of CdCl2=0.61 mg of Cd) for

onetime and killed after one week. Total Cd = 0.61 mg. Mice 4 and 5 were

given 50 mgof ointment (1 mg of CdCl2=0.61 mg of Cd) for four times in one week

and killed afterone week. Total Cd=2.44mg.

Applicant's summary and conclusion

Conclusions:
Application of a 1% solution of CdCl2 or of a 2% ointment of the same compound to the shaved skin of rabbits for 5 weeks or to hairless mice for 2 weeks indicated substantial percutaneous absorption of Cd which accumulated, two weeks after the end of exposure, in kidney and liver at 0.4-0.6 and 0.2-0.8 % of the dose in rabbits and mice, respectively. However, only cadmium contents of liver and kidney were measured, so total absorption through the skin may have been greater.
Executive summary:

This study describes the percutaneous absorption of cadmium as estimated from the accumulation of cadmium in the liver and kidneys of mice and rabbits.

Male rabbits were dosed with cadmium chloride percutaneously with a 1% aqueous solution (6.1 mg cadmium) or 2% ointment (12.2 mg cadmium) over a 10-cm2 shaved area. Animals were treated 5 times over 3 weeks and were killed 2 weeks after the last application. Only cadmium contents of liver and kidney were measured, so total absorption through the skin may have been greater. Similarly, male hairless mice were dosed with cadmium chloride percutaneously with a 2% ointment (containing 0.61 mg cadmium) 1 or 5 times in a week (duration of exposure not reported) and killed 1 week later.

Application of a 1% solution of CdCl2 or of a 2% ointment of the same compound to the shaved skin of rabbits for 5 weeks or to hairless mice for 2 weeks indicated substantial percutaneous absorption of Cd which accumulated, two weeks after the end of exposure, in kidney and liver at 0.4-0.6 and 0.2-0.8 % of the dose in rabbits and mice, respectively.