Lanthanum oxide

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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

A kinetic study of radionuclide absorption through damaged and undamaged skin of the guinea pig

Author:

Inaba. J, Suzuki-Yasumoto, M

Year:

1979

Bibliographic source:

Health Psych. 37 (4), 592-595

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Absorption of radiolabelled 144CeCl3 through guinea pig skin was determined in anaesthetized animals by observation of the radiolable on the skin and distribution in skin and body after 3 hr of exposure.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Cerium trichloride

EC Number:

232-227-8

EC Name:

Cerium trichloride

Cas Number:

7790-86-5

Molecular formula:

CeCl3

IUPAC Name:

cerium(3+) trichloride

Details on test material:

- Name of test material (as cited in study report): 144cerium trichloride equilibrated with the daughter 144Pr.
- Molecular formula (if other than submission substance): CeCl3
- Molecular weight (if other than submission substance): 246.45
- Structural formula attached as image file (if other than submission substance): see Fig. CeCl3
- Substance type: solid salt
- Physical state: solid
- Analytical purity: no tstated
- Specific activity (if radiolabelling): 20 mCi/mg Ce
- Locations of the label (if radiolabelling): Ce

Radiolabelling:

yes

Remarks:

144CeCl3 paired with 144Pr

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not stated
- Age at study initiation: adult
- Weight at study initiation: 500 g
- Anaesthesized with Nembutal (Abbot)

.

Administration / exposure

Type of coverage:

open

Vehicle:

other: solution in 1.1 N HCl diluted with distilled water to 100 micro-Ci/ml solution (pH 2)

Duration of exposure:

3 hours

Doses:

- Actual doses: 1 micro-Ci/cm2 skin
- Dose volume: 0.01 ml/cm2 skin

No. of animals per group:

3 animals

Details on study design:

TEST SITE
- Preparation of test site: After the animal had been anesthetized, the hair on the right led skin was shorn with an electric clipper and about 2 cm2 of the epridermal part of the shorn skin surface was stripped away with strong transparent adhesive tape (seven to 8 times stripping). The intact hairless skin was prepared by shearign the surface of the skin of the right leg and plucking out the fine hairs with a finepointed foreceps in an area of about 2 cm2. On the day of the experiment the plucked skin was lightly shaved with a razor and the area carefully examined under a magnifying glass for possible lesions. If lesions were detected the animal was not used.
- Area of exposure: 1 cm2 stipped skin and 1cm2 intact skin.

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes: The anesthetize animal was fixed to a plastic board with an adhesive tape.

Application of the test substance: 0.01 ml of the radioactive solution was applied with a micropipette to 1 cm2 of skin and dried within 1 to 2 min with an electric hair dryer.

Detection: Beta-radioactivity was measured with a catheter type semiconductor radiation detector (Toshiba, Tokyo) conmnected to a 200-channel pulse height analyzer (Toshiba). A plastic collar was attached to the top of the detector to minimize variation in counting efficiency. The detctor was placed in a stand holder, a pulse-height analyser was used as a multichannel scaler. The measurement time per one channel was set to 100 sec.

After drying of the test substance the collar of the detector was placed in direct contact with the exposed skin area without exerting pressure. Radioactivity was measured for 3 h.

After 3 h the animal was killed by injection of an overdose of Nembutal and the exposed skin area was dissected. The radioactiviy in the dissected skin, the remaining whole body and the excreta collected during the exposure period was analysed by an Armac counter (Packard).

Two other substances were also tested in the same system (60Co and 137 Cs).

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

- Skin test site: during the 3 h exposure period 144Ce-Pr radioactivity remained constant in the exposed skin area in both stripped and intact skin. (The other 2 test materials showed a considerable decay in stripped skin during that period indicating sensitivity of the test system).
In the dissected skin the loss of 144Ce radioactivity was calculated from the difference in radioactivity in dissected skin, the remainder of the body and excreta. The absorption was calculated to be 4 +- 3% in stripped skin and <= 0.001 +- 0.001% in intact skin (n=3, mean +- SD). The value of 0.001 % was very close to the detection limit of the method.

Total recovery:

not stated

Percutaneous absorption

Dose:

1 micro Ci

Parameter:

percentage

Absorption:

<= 0.001 %

Remarks on result:

other: 3 h

Remarks:

intact skin

Applicant's summary and conclusion

Conclusions:

The study demonstrated that absorption of a soluble cerium salt, cerium trichloride through intact guinea pig skin is very low (<= 0.001%). It can be assumed that the uptake of less soluble compounds is even lower. Cerium3+ can in this case be used as a surrogate for lanthanum oxide as well, because the atomic radius is very of the two metals is very similar and the oxidation state is the same (3+). It can therefore be concluded that dermal absorption of lanthanum oxide through intact skin can be considered negligible.

Executive summary:

Inaba et al (1979) studied the uptake of radiolabled Cerium chloride (144Ce) through stripped and intact guinea pig skin during a 3 hour exposure period. The uptake through intact skin was negligible (<= 0.001%) while from stripped skin ca. 4% of the radioactivity were absorbed. The study demonstrated that absorption of a soluble cerium salt, cerium trichloride through intact guinea pig skin is very low (<= 0.001%). It can be assumed that the uptake of less soluble compounds is even lower. Cerium3+ can in this case be used as a surrogate for lanthanum oxide as well, because the atomic radius is very of the two metals is very similar and the oxidation state is the same (3+). It can therefore be concluded that dermal absorption of lanthanum oxide through intact skin can be considered negligible.