Safety limit estimation for cataract induced by ultraviolet radiation

Abstract: Background: Ultraviolet radiation (UVR) is considered one of the major risk factors for agerelated cataract. UVR-induced cataract follows a continuous dose-response function. The concepts maximum acceptable dose (MAD) and its improvement, maximum tolerable dose (MTD), were developed for estimation of threshold dose for avoidance of UVR-induced cataract. The present report details the results of our research investigating the impact of age, exposure time, and interexposure interval for double exposures on threshold dose. Methods: Lenses from female Sprague-Dawley outbred rats were exposed to UVR type B (UVR-B). The radiation from a high-pressure mercury arc lamp was collimated, passed through a water filter and a double monochromator (lambda(max) =300 nm), and projected in vivo on the cornea or in vitro on the anterior surface of lens. One week after in vivo UVR-B exposure, extracted lenses were photographed and forward light scattering was measured. After in vitro UVR-B exposure, both exposed and nonexposed lenses were cultured. The intensity of forward light scattering was measured daily during week 1 and every second day during weeks 2 and 3. Morphologic changes were documented. Results: The MAD for 3-week-old rats was almost 3 times lower than that for 18-week-old rats (study I). Rats aged 18 to 60 weeks had a stable MTD of approximately 5 kJ/m2 (study II). The data from rats aged 3 to 60 weeks were used to derive a general expression for threshold dose (MTD) as a function of rat life span. It was shown that MTD increases with increasing age in the first third of the life and then remains stable for the remaining two thirds of the life span. The study of lenses exposed in vitro to UVR-B proved that the sensitivity difference between young and old rats does not depend on age-related anatomic differences (study III). With varying exposure times (7.5, 15, 30, 60, or 120 minutes), it was found that there was a lowest threshold dose at 15 minutes of UVR-B exposure (study IV). When varying intervals between 2 repeated exposures at a constant UVR-B dose, it was found that the 1 day interexposure interval was associated with a lower threshold dose than the interexposure intervals 6 hours, and 1, 3, 9, and 30 days (study V).