Fatty acids, C14-18 and C16-18-unsatd., barium salts

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

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

Adequacy of study:

supporting study

Rationale for reliability incl. deficiencies:

other: Reasonable well documented case-report on a single woman

Data source

Reference

Reference Type:

publication

Title:

Human Cell-Dysplasia following barium

Author:

Ayre, J.E.

Year:

1966

Bibliographic source:

Ind.Med. Surg., 35: 393-399.

Materials and methods

Study type:

medical monitoring

Endpoint addressed:

carcinogenicity

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

The report represents a study of effects of a specific chemical component used in a number of plastic devices, namely, barium. A solution of 1.25 X 10^-3M barium chloride was applied directly to the cells of the squamocolumnar junction and the endocervix to observe cellular response and morphological structural change. The cervical scrape technique was employed in this study, which determines cell response or structural cell change prior to and during the process of physiological exfoliation.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Barium chloride

EC Number:

233-788-1

EC Name:

Barium chloride

Cas Number:

10361-37-2

IUPAC Name:

barium dichloride

Details on test material:

- Name of test material (as cited in study report): Barium chloride
No further information on the test material was stated.

Method

Type of population:

general

Ethical approval:

not specified

Details on study design:

A solution of 1.25 X 10^-3 M barium chloride was used and applied topically to the cervix with a swab applicator held in direct contact with the tissues of the cervical os (mouth) of the squamocolumar junction. Forty-eight hours after application, a cervical cell scraping was made from the same precise squamocolumnar junctional area of the cervix and the squamous and endocervical cells subsequently examined for possible change.
On three separate occasions barium was applied to the cervix at intervals of four to six weeks.
In a second experiment, DMSO 90% was mixed with 1.25 x 10^-3 M barium chloride in equal amounts. The barium-DMSO mixture was applied directly to the squamocolumnar junctional area of the cervix. During the second experiment with the barium-DMSO mixture,cell scrapings were collected from the area forty-eight hours after application, again at 72 hours, and continuing twice weekly.
No further details on study design was stated.

Results and discussion

Results:

After each topical application of barium chloride the cell change appeared and then faded away after cell exfoliation.
The changes noted in the cells in the cervical scrape test following the use of barium chloride were:
1. Multinucleation and multilobulation appeared in cells which previously exhibited normal structural form with extremely marked multinucleation to three, to five, or more, separate or conglomerate nuclei.
2. The altered cells showed an increase in cytoplasmic volume with some tadpole forms.
3. Abnormal nuclei frequently showed marked enlargement and irregularity in shape.
4. Some of the cells showed an increase in hyperchromatism of the nuclei, similar to that observed in cervical dysplasia. Others exhibited structural change but the nuclei were clear and vesicular.
5. Leukoplakic cells were noted with characteristic "ghost" nuclei singly and in sheets of acidophilic cells.
6. Clusters of cells from the endocervix exhibited similar changes with desquamation in sheets or clumps - a manifestation rarely observed in cytologic research.
7. The multinucleated cells exhibited increased nuclear DNA and some increased RNA activity in cytoplasm under fluorescent microscopy similar to findings in mild dysplasia.
8. Cellular changes present 48 hours after application of the barium faded out and disappeared one to two weeks following the application of the barium solution.
During the second study with the barium-DMSO mixture the following findings were made:
The dysplasitc cells previously observed when treated with barium alone were present, but a remarkable change had taken place in the total cell picture, with cell alteration to extreme dysplasia and cells exhibiting a striking resemblance to those exfoliated in carcinoma in situ. For the first time, spindle cells were noted as well as cells whose nuclei showed marked hyperchromatism with multiple chromatin bundles and enlarged, irregular, nucleated forms. the findings demonstrated that DMSO had dramatically intensified the cellular response to barium chloride. All grades of dysplasia were increased. Cells of a deeper origin in the epithelium were observed with diminution of the multinucleated type of cell arising from the intermediate and superficial areas of the epithelium. By the 16th day, the cellular lesions had partially regressed. Chiefly cells of superficial and intermediate areas showing multinucleation persisted, while the deeper dysplasic forms of basal and parabasal origin has apparently exfoliated and disappeared from cytologic view.

Applicant's summary and conclusion

Conclusions:

A single, local, topical administration of BaCl2 resulted in the transformation of cervical epithelial cells into bizarre, multinucleated cells with profound alterations of the nuclear chromatin characteristic of pre-malignant dysplasia. Two to three weeks after the application, the dysplastic cells had been exfoliated with complete regression to normal. Two-fold repetition of the experiment on the same subject resulted in the same results each time.
A second experiment with a barium chloride/ DMSO mixture showed that DMSO, acting as a high power conductor, carries the barium into the living cervical cells, penetrates the cell walls, intensifies the barium response in these cells, and affects deeper layers of the suamous epithelium. Cells, chiefly of squamous type, were observed, with a smaller number of altered endocervical gland cells showing the same type of change previously observed under the influence of barium alone.