Registration Dossier

Administrative data

Description of key information

The substance was not carcinogenic to mice after dermal application.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Male and female Swiss-Webster mice were dermally treated with aqueous solutions of dihydroxyacetone once per week for 80 weeks.
- Short description of test conditions: 1 Control and 2 test item groups were included in this study. Each animal receive
- Parameters analysed / observed: mortality, behaviour, general appearance, body weight, gross examination at necropsy, histopathology.
GLP compliance:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source of test material: Wallerstein Laboratories
- Purity: >97%

Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Route of administration:
dermal
Vehicle:
water
Details on exposure:
Once each week mice received a 0.1 mL application of one of the test item 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
Dose / conc.:
50 000 ppm (nominal)
Remarks:
5% aqueous solution
Dose / conc.:
400 000 ppm (nominal)
Remarks:
40% aqueous solution
No. of animals per sex per dose:
50 animals per sex per dose
(in total: 300 animals)
Control animals:
yes, concurrent vehicle
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 died 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
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
no effects observed
Mortality:
mortality observed, non-treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
effects observed, non-treatment-related

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.

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification