Registration Dossier

Administrative data

Endpoint:
carcinogenicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientific publication in peer reviewed journal.

Data source

Reference
Reference Type:
publication
Title:
Non-carcinogenicity of Dihydroxyacetone by skin painting
Author:
Akin FJ., Marlowe E.
Year:
1984
Bibliographic source:
J Environ Pathol Toxicol Oncol, 5, 349 - 351

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Male and female Swiss-Webster mice were dermally treated with aqueous solutions of dihydroxyacetone once per week for 80 weeks.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
DHA (Wallerstein Laboratories)
Purity: > 97 %

Test animals

Species:
mouse
Strain:
Swiss Webster
Sex:
male/female

Administration / exposure

Route of administration:
dermal
Vehicle:
water
Details on exposure:
Once each week mice received a 0.1 mL application of one of the dihydroxyacetone solutions (5 or 40%) or distilled water. The solutions were spread evenly over the shaved back of each animal.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
80 weeks
Frequency of treatment:
once per week
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1 mL of aqueous DHA solution (5 or 40%)
Basis:
nominal in water
No. of animals per sex per dose:
50/50 male/female per dose
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
Mice were examined daily for survival, behavior, and general appearance. They were weighed weekly during the first 26 weeks, biweekly through the 52nd week and at monthly intervals thereafter.
Sacrifice and pathology:
All mice that dies and those that were sacrificed in moribund conditions were examined grossly at necropsy and fixed in formalin. The following tissues were examined for tumors and/or abnormalities: Skin, liver, spleen, stomach, small and large intestines, kidney, bladder, adrenals, gonads, uterus, pituitary, thyroid, thymus, salivary glands, axillary lymph nodes, lung, and brain. Tumors were fixed for microscopic examination.
Statistics:
At the termination of the study, survival, weight gains, and all solid and non-solid tumors in the various groups were compared statistically

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Any other information on results incl. tables

Except for the brown coloration of application sites in DHA-treated mice, no differences in gross physical appearance and clinical signs were observed. Body weight gains were similar in all groups. Survival rate was not affected by DHA treatment. At histopathological examination, there were no changes attributed to treatment with DHA. The tumours observed were typical of the type normally observed in mice of this strain and age, and they were equally distributed among control and treated groups. The authors concluded that DHA was not carcinogenic in mice after weekly topical application for 80 weeks.

Applicant's summary and conclusion

Conclusions:
In summary, no significant differences were seen in this study between control mice and those treated with the two levels of DHA. Lesions appearing in these animals were typical of the type normally seen in aged mice. It was concluded that chronic administration of DHA did not induce any carcino¬genic effects nor were there any increases in the incidence of leukemias or lymphomas with the application of this material.
Executive summary:

The carcinogenic potential of DHA after dermal application was investigated in Swiss-Webster mice. Animals were treated by topical application with aqueous solutions of DHA (5 or 40%) on the shaved dorsal regions once weekly for 80 weeks. Except for the brown coloration of application sites in DHA-treated mice, no differences in gross physical appearance and clinical signs were observed. Body weight gains were similar in all groups. Survival rate was not affected by DHA treatment. At histopathological examination, there were no changes attributed to treatment with DHA. The tumours observed were typical of the type normally observed in mice of this strain and age, and they were equally distributed among control and treated groups. The authors concluded that DHA was not carcinogenic in mice after weekly topical application for 80 weeks.