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Administrative data

additional toxicological information
Type of information:
experimental study
Adequacy of study:
other information
Study period:
Not applicable
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference Type:
study report
Report date:

Materials and methods

Type of study / information:
Peer Review of Skin Painting Study Concerning Valeric Acid in C3H Mice
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Valeric acid
EC Number:
EC Name:
Valeric acid
Cas Number:
Molecular formula:
pentanoic acid

Results and discussion

Any other information on results incl. tables

Since it was assumed that all mice died at some point during the study, all mice were grouped together for purposes of reporting results. There were 48 mice in the control group and 50 mice in the test chemical group.

There were more neoplasms diagnosed in the liver of the control mice which can probably be accounted for by the fact that not all tissues were presented for diagnoses from the test material mice. The quality of the materials (slides) was very poor, both with respect to the organization of the tissue that was present on the slides as well as the sectioning and staining, making the interpretation very difficult in some cases.

One of the lesions that is of higher incidence in the control animals than in the test animals is mite infestation, which was accompanied by acanthosis and mild hyperkeratosis, with an occasional area of inflammation. This infestation seemed to be present primarily in the mice that were numbered in the 1500 to 2500 range, and not in the others, making this reviewer wonder if the animals were housed in different rooms. Had the mite infestation not been present in the control mice, the incidence of acanthosis and hyperkeratosis would have been much lower in that group.

The most obvious differences between the groups was observed in the treated skin where the test material group had many neoplasms diagnosed, whereas the control group did not. The incidence of melanosis and fibrosis in the test mice was particularly interesting, as was the fact that in three animals fibrosarcomas were found. It was debatable if the instance of severe fibrosis in one mouse should also be called a fibrosarcoma, but the decision was made not to do so because of the multifocal nature of the lesion.

The papillomas and squamous cell carcinomas seen in the test mice are an indication that the test material was carcinogenic in this test system. If the mice used were C3H mice, as suspected, these mice rarely get spontaneous squamous cell carcinomas in our experience. When this fact is taken together with the fact that the controls did not have any neoplasias of the skin, this provides strong evidence for the carcinogenic nature of the test material.

Applicant's summary and conclusion

The reaction in the treated skin indicated the valeric acid to be a strong irritant, causing acanthosis, hyperkeratosis, fibrosis, melanosis, dermatitis, and ulceration.
Executive summary:

A peer review of two groups of mice used in a skin painting study at the University of Cincinnati was requested by Dr. Tipton Tyler, representing the interests of the Solvents and Coatings Division of the Union Carbide Chemicals and Plastics Company Inc. The groups of mice submitted were the control group, painted with mineral oil, and a group that was painted with valeric acid, labeled as Compound C-180. The mice were presumably male C3H mice, although no protocol was submitted with the slides.

The test material, Compound C-180, was carcinogenic to the skin under the conditions of this test. Six squamous cell carcinomas, and two papillomas, were found in the treated skin of the 50 mice in the test group, whereas no such tumors were found in the treated skin of the 48 mice examined in the control group. In addition, three of the mice from the test group were found to possess fibrosarcomas in the treated skin area. The reaction in the treated skin indicated the valeric acid to be a strong irritant, causing acanthosis, hyperkeratosis, fibrosis, melanosis, dermatitis, and ulceration.