1,3-dihydroxyacetone

Carcinogenicity

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