National Toxicology Program

TR-553
Photocarcinogenesis Study of Aloe Vera [CAS NO. 481-72-1(Aloe-emodin)] in SKH-1 Mice (Simulated Solar Light and Topical Application Study)

PLEASE NOTE: The following abstract has been extracted from the DRAFT technical report to be reviewed by the National Toxicology Program Board of Scientific Counselors Technical Reports Review Subcommittee on February 27-28, 2008 (see the meeting page). When this report becomes final the entire report will be available in pdf format on the NTP website.

Draft Abstract

The popular recognition of the Aloe barbadensis Miller (Aloe vera) plant as a therapeutic dermatologic agent has led to the widespread incorporation of Aloe vera leaf extracts in skincare products. Studies have suggested that Aloe vera in skincare preparations may synergize with ultraviolet radiation and enhance skin cancer. A 1-year study was conducted in mice to determine whether the topical application of creams containing Aloe vera plant extracts (aloe gel, whole leaf, or decolorized whole leaf) or creams containing aloe-emodin would enhance the photocarcinogenicity of simulated solar light (SSL).

1-YEAR STUDY

Groups of 36 male and 36 female Crl:SKH-1 (hr ^-/hr ^-) hairless mice received topical applications of control cream or creams containing 3% or 6% (w/w) aloe gel, whole leaf, or decolorized whole leaf or 7.46 or 74.6 µg/g aloe-emodin to the dorsal skin region each weekday morning. The mice were irradiated with SSL emitted from filtered 6 kW xenon arc lamps each weekday afternoon. The topical applications of creams and irradiance exposures were conducted 5 days per week for a period of 40 weeks. A 12-week recovery/observation period followed the 40-week treatment/exposure period. Additional groups of 36 male and 36 female mice received no cream and were exposed to 0.00, 6.85, 13.70, or 20.55 mJCCIE/cm² SSL per day.

Mice that received no cream treatment and were exposed to increasing levels of SSL showed significant SSL exposure-dependent decreases in survival and significant increases in the in-life observations of skin lesion onset, incidence, and multiplicity, and significant SSL exposure-dependent increases in the incidences and multiplicities of histopathology determined squamous cell nonneoplastic skin lesions (squamous hyperplasia and focal atypical hyperplasia) and squamous cell neoplasms (papilloma, carcinoma in situ, and/or carcinoma). Squamous cell neoplasms were not detected in mice that received no SSL exposure.

The topical treatment with the control cream of mice that were exposed to SSL did not impart a measurable effect when compared with comparable measurements in mice that received no cream treatment and were exposed to the same level of SSL, suggesting that the control cream used in these studies did not alter the efficiency of the SSL delivered to mice or the tolerability of mice to SSL.

The application of aloe gel creams to mice had no effect on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity. The administration of aloe gel creams to male mice had no effect on the incidences or multiplicities of histopathology-determined squamous cell nonneoplastic skin lesions or neoplasms. Female mice treated with aloe gel creams (3% and 6%) had significantly increased multiplicities of squamous cell neoplasms.

There were no treatment-related effects on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity in mice treated with the whole leaf creams. In male mice exposed to SSL and treated with the 6% whole leaf cream, a significant increase was observed in the multiplicity of squamous cell neoplasms. Female mice exposed to SSL and treated with the 3% whole leaf creams had significantly decreased multiplicity of squamous cell nonneoplastic lesions and significantly increased multiplicity of squamous cell neoplasms. Female mice exposed to SSL and treated with the 6% whole leaf cream had significantly decreased multiplicity of squamous cell nonneoplastic lesions.

The application of decolorized whole leaf creams to mice had no effect on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity. Male mice administered the 3% decolorized whole leaf cream had significantly increased multiplicity of squamous cell neoplasms. Female mice administered the 3% decolorized whole leaf cream had significantly decreased multiplicity of squamous cell nonneoplastic skin lesions and significantly increased multiplicity of squamous cell neoplasms. In female mice that received the 6% decolorized whole leaf cream, there was a significant increase in the multiplicity of squamous cell neoplasms.

As with the Aloe vera plant extracts, the application of aloe-emodin creams to mice had no measurable effect on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity. The administration of aloe-emodin creams to male mice had no effect on the incidence or multiplicity of histopathology determined nonneoplastic skin lesions or squamous cell neoplasms. Female mice treated with the 74.6 µg/g aloe-emodin cream had significantly decreased multiplicity of histopathology-determined squamous cell nonneoplastic skin lesions and significantly increased multiplicity of squamous cell neoplasms.

CONCLUSIONS

In male and female SKH-1 hairless mice treated topically with aloe gel creams and exposed to SSL, the onset, incidence, and multiplicity of in-life observed skin lesions and the incidence of squamous cell neoplasms (papilloma, carcinoma in situ, and carcinoma) did not differ from comparable measurements made in mice treated with control cream and exposed to SSL. The multiplicity of squamous cell neoplasms was significantly increased in female, but not male, mice treated topically with aloe gel creams and exposed to SSL, when compared to mice treated with control cream and exposed to the same dose of SSL.

In male and female SKH-1 hairless mice treated topically with aloe whole leaf creams and exposed to SSL, the onset, incidence, and multiplicity of in-life observed skin lesions and the incidence of squamous cell neoplasms did not differ from the comparable measurements made in mice treated with control cream and exposed to SSL. The multiplicity of squamous cell neoplasms was significantly increased in mice treated topically with aloe whole leaf creams and exposed to SSL, when compared to mice treated with control cream and exposed to the same dose of SSL.

In male and female SKH-1 hairless mice treated topically with decolorized aloe whole leaf creams and exposed to SSL, the onset, incidence, and multiplicity of in-life observed skin lesions and the incidence of squamous cell neoplasms did not differ from the comparable measurements made in mice treated with control cream and exposed to SSL. The multiplicity of squamous cell neoplasms was significantly increased in mice treated topically with decolorized aloe whole leaf creams and exposed to SSL, when compared to mice treated with control cream and exposed to the same dose of SSL.

In male and female SKH-1 hairless mice treated topically with aloe-emodin and exposed to SSL, the onset, incidence, and multiplicity of in-life observed skin lesions and the incidence of squamous cell neoplasms did not differ from the comparable measurements made in mice treated with control cream and exposed to SSL. The multiplicity of squamous cell neoplasms was significantly increased in female mice, but not male mice, treated topically with aloe-emodin creams and exposed to SSL, when compared to mice treated with control cream and exposed to the same dose of SSL.

Synonyms: Aloe barbadensis Miller; Aloe vera Tournefort ex Linné; Aloe vulgaris Lamark; Barbados aloe; Curaçao aloe

Summary of the 1-Year Photococarcinogenesis Study of Aloe vera and 13.70 mJ⋅CIE/cm² SSL in SKH-1 Mice

^aThe number of skin lesions per animal at risk in the group

Summary of the 1-Year Photococarcinogenesis Study of Aloe vera and 13.70 mJ⋅CIE/cm² SSL in SKH-1 Mice

^aThe number of skin lesions per animal at risk in the group

Pathology Tables, Survival and Growth Curves from NTP 2-year Studies