Rates of allergic sensitization and irritation to oxybenzone-containing sunscreen products: a quantitative meta-analysis of 64 exaggerated use studies.

BACKGROUND/PURPOSE: Oxybenzone is an active ingredient found in sunscreen products that absorbs a broad spectrum of ultraviolet (UV) light, with absorbance peaking in the UVB region and extending into the UVA region. Although the overall incidence of sensitization and irritation associated with oxybenzone in the general population remains unclear, a few studies have reported on the incidence in specific circumstances. However, the relevance of these studies to the general population is limited, because the sample populations reported in these papers generally have consisted of individuals who sought medical attention for pre-existing skin conditions. Therefore, the reported incidence of allergic reactions to oxybenzone in these studies may be overestimated as related to the general population. The objective of this meta-analysis was to determine the safety of oxybenzone in participants recruited from the general population. METHODS: The data from 64 unpublished exaggerated use human repeat insult patch tests (HRIPT) and photoallergy (PA) studies sponsored by Schering-Plough HealthCare Products Inc. between 1992 and 2006 were aggregated and analyzed to evaluate the irritancy and sensitization potential of sunscreen products containing oxybenzone at concentrations between 1% and 6%. RESULTS: Forty-eight of 19 570 possible dermal responses were considered to be suggestive of irritation or sensitization; the mean rate of responses across all formulations was 0.26%. Sensitization rates did not correlate significantly with oxybenzone concentration. The available re-challenge data indicated that only eight of these responses were contact allergies from oxybenzone, and the mean rate of contact allergy to oxybenzone was 0.07%. The source of the skin responses was not confirmed for 15 subjects who were lost to follow-up. However, all subjects were given the opportunity to participate in follow-up testing. CONCLUSION: Our data indicate that sunscreen products formulated with 1-6% oxybenzone do not possess a significant sensitization or irritation potential for the general public. Furthermore, these data suggest that the incidence rate implied in the published literature overestimates the actual incidence of sensitization/irritation due to oxybenzone-containing sunscreen products in the general population.

Chronic toxicity and oncogenicity study with glutaraldehyde dosed in the drinking water of Fischer 344 rats.

Glutaraldehyde (GA) has a wide spectrum of industrial, scientific and biomedical applications. Its potential to produce chronic toxic and/or oncogenic effects was investigated in Fischer 344 rats (100/sex/group) given GA in drinking water for a maximum of 104 weeks. GA concentrations were 0 (control), 50,250 and 1000 ppm, resulting in average daily GA consumptions, respectively, of 0, 4, 17 and 64 mg/kg for males and 0, 6, 25 and 86 mg/kg for females. Interim euthanasia (10/sex/group) was performed at 52 and 78 weeks. Parameters evaluated were clinical signs, body weight, food and water consumption, hematology, serum chemistry, urinalysis, organ weights, gross and microscopic pathology. There were no treatment-related effects on mortality. Absolute body weights and body weight gains of the 250 and 1000 ppm males and females were reduced over the study in a dosage-related manner. Food and water consumption by the 250 and 1000 ppm groups were decreased in a statistically significant dose-related manner over the study, and mean water consumption by the 50 ppm animals was slightly reduced but not with statistical significance. The 250 and 1000 ppm groups had a dose-related decrease in urine volume with increased osmolality, and pH was slightly reduced. Absolute kidney weights were increased in the 250 and 1000 ppm groups at the 52 and 78 week sacrifices, and decreased at 104 weeks. Relative kidney weights were increased at all sacrifice times for the 1000 ppm group, at 52 weeks for the 250 ppm group, and at 72 weeks for the 50 ppm group. The urinalysis and renal weight changes are compatible with a physiological compensatory adaptation to reduced water consumption. Gross and histological evidence for gastric irritation was observed principally in the 1000 ppm rats euthanized at 104 weeks and in animals that died during the study. Bone marrow hyperplasia and renal tubular pigmentation, seen in rats that died and the 104 week euthanasia animals, may have been secondary to a low grade hemolytic anemia in animals with large granular lymphocytic leukemia (LGLL). The only neoplasm that showed a statistically significant increase was LGLL, which occurred at a high incidence in both sexes and all groups, including the controls, for both animals that died and at the 104 week euthanasia. A few instances of LGLL were observed at 78 weeks. The overall incidence of LGLL in the spleen for the 0, 50, 250 and 1000 ppm groups was, respectively, 43, 51, 40 and 46% for males, and 24, 41, 41 and 53% for females. Statistical analyses indicated that the severity of LGLL was associated with the higher dosages of GA in female, but not male, rats. Due to the background and variable incidence of LGLL in the Fischer 344 rat, the finding of a statistical significance only for female rats, and because, there was no clear dose-response relationship, the biological significance of the LGLL findings is unclear. There is the possibility that the significance was a statistical artifact due to the low incidence of LGLL in the female control animals as a result of biological variability within the study. It is also considered to be possible that the chronic dosage of GA in the drinking water resulted in a modification of one or more of the factors responsible for the expression of this common and spontaneously occurring neoplasm in the Fischer 344 rat.