Implications of laboratory tests of condom integrity.

BACKGROUND: There is sufficient evidence from Food and Drug Administration laboratory experiments and clinical studies to draw conclusions about the relative importance of holes and breakage to condoms. The laboratory test methods determined penetration of viruses or virus-size microspheres through holes in condoms under conditions that simulated or exaggerated those expected in actual use, and determined the frequency with which condoms might pass virus or microspheres and the amounts of passage in each case. GOALS: To summarize and comment on the significance of test results on latex, polyurethane, and natural membrane condoms as barriers to virus passage. STUDY DESIGN: Published and unpublished data addressing three distinct concerns were analyzed: (1) passage of virus or microspheres through small holes or pores inherent in the material of "intact" condoms which are undetectable by the standard water leak quality assurance test, (2) passage of virus or microspheres through larger holes in "leaker" condoms detectable by the water leak test but marketed because of the finite acceptable quality level (AQL) of the test, and (3) passage of virus through condoms that break during use. RESULTS: Extrapolating to the passage of semen expected during actual use allowed an analysis of the relative importance of breakage and water-leak-detectable or water-leak-undetectable holes. CONCLUSIONS: The relative importance of breaks and holes is related to the volume of semen that contains an "infectious dose" of a sexually transmitted disease (STD). When 0.1 mL to 1.0 mL exposures to semen are necessary for disease transmission, the risk during latex condom use primarily results not from holes, but from breakage of condoms. For smaller volumes of semen exposure (0.00001 mL and less), the presence of holes can be as important as breaks. The same qualitative argument pertains to a comparison of "leaker" condoms to the large majority of "intact" condoms.

PIP: This study examines the significance of test results on latex, polyurethane, and natural membrane condoms as barriers to virus passage. Data on three distinct concerns were analyzed: 1) passage of virus or microspheres through small holes or pores inherent in the material of "intact" condoms which are undetectable by the standard water leak quality assurance test; 2) passage of virus or microspheres through larger holes in "leaker" condoms detectable by the leak test but marketed because of the finite acceptable quality level of the test; and 3) passage of virus through condoms that break during use. The results showed that relative importance of breaks and holes is related to the volume of semen that contains an "infectious dose" of a sexually transmitted disease. When 0.1-1.0 ml exposures to semen are necessary for disease transmission, the risk during latex condom use primarily results not from holes but from breakage of condoms. For smaller volumes of semen exposure (0.00001 ml or less), the presence of holes can be as important as breaks. The same qualitative argument pertains to a comparison of "leaker" condoms to the large majority of "intact" condoms.

An analysis of UVA emissions from sunlamps and the potential importance for melanoma.

Exposure to solar UV radiation is a risk factor for cutaneous malignant melanoma (CMM). Epidemiologic studies have also considered the use of sunlamps as a possible contributor to CMM. We measured and analyzed the emission spectra of six different currently marketed sunlamps and a historical sunlamp, the UVB-emitting FS lamp, and compared the results to solar exposure. For a typical tanner (20 sessions @ 2 minimal erythema doses (MED)/session), the annual UVA doses from commonly used fluorescent sunlamps were 0.3-1.2 times that received from the sun. For a frequent tanner (100 sessions @ 4 MED/session), the annual UVA doses from fluorescent sunlamps were 1.2-4.7 times that received from the sun and 12 times for recently available, high-pressure sunlamps. To determine biologically effective doses, action spectra for squamous cell carcinoma (SCC) in humans and for melanoma in the Xiphophorus fish (XFM) were applied to the sunlamps' emission spectra. The results for the effective doses using the SCC action spectrum tracked the UVB doses, while the results using the XFM action spectrum tracked the UVA doses. When combined with UV exposure received from the sun, typical sunlamp use results in an approximate doubling of annual effective dose, if the XFM action spectrum is applied. Frequent use, however, can increase the annual effective XFM dose by as much as 6 times what would be received from the sun alone for fluorescent sunlamps and as much as 12 times for newer, high-pressure sunlamps.

A sensitive method for evaluating condoms as virus barriers.

A standard test is needed to evaluate condoms as barriers against sexually transmitted diseases, particularly those caused by viruses. The proposed method presented here consists of a previously published simple method using physiologic-based conditions plus improvements to increase test sensitivity and decrease confounding factors such as contamination. Limitations of the method were determined by measuring virus penetration through small, well-defined holes. The method can detect penetration of 2 nL (2 x 10(-6) mL) of challenge virus suspension as well as a hole of 2 microns diameter in a latex condom. The data also indicated that virus penetration of latex condoms occurred quickly, and the hole was then apparently closed or blocked.

PIP: Condoms can act as barriers to the passage of sexually transmitted diseases (STDs). However, a claim that condoms are effective against STDs must be confirmed by appropriate laboratory tests. Various tests have therefore been developed to evaluate the barrier effectiveness of latex and natural membrane condoms. The authors describe and evaluate a test which involves filling the condom with virus-containing buffer and determining whether any virus penetrates the barrier during submersion in a collection buffer. Virus penetration is measured and reported as the equivalent volume of challenge virus suspension needed to account for the amount of virus penetration. The limitations of this approach were determined by measuring virus penetration through small, well-defined holes. It was found that the method can detect penetration of 2 nl of challenge virus suspension as well as a hole of 2 mcm diameter in a latex condom. The data also indicate that virus penetration of latex condoms occurs quickly, then the hole apparently closes or is blocked.

An in vitro evaluation of condoms as barriers to a small virus.

BACKGROUND: Because of the possible presence of small holes, the effectiveness of condoms as barriers to virus transmission is controversial. GOALS: To determine the proportion of condoms that allow virus penetration and the amounts of virus that penetrate. STUDY DESIGN: A sensitive, static test was used to evaluate different condom types as barriers to a small virus, including brand with or without lubrication and ones of different materials. The test included some physiologic-based parameters and some parameters that exaggerated expected actual use conditions. RESULTS: Under test conditions, 2.6% (12 of 470) of the latex condoms allowed some virus penetration; the median level of penetration was 7 x 10(-4) ml. Lubricated condoms performed similarly to nonlubricated ones. Polyurethane condoms yielded results higher than but not statistically different from those for latex condoms. CONCLUSIONS: Few condoms allowed any virus penetration. The median amount of penetration for latex condoms when extrapolated to expected actual use conditions was 1 x 10(-5) ml (volume of semen). Thus, even for the few condoms that do allow virus penetration, the typical level of exposure to semen would be several orders of magnitude lower than for no condom at all.

PIP: Nine brands and 470 samples of latex condoms and two brands and 76 samples of polyurethane condoms bought from retail distributors were tested in vitro for their ability to block the penetration of virus. A sensitive, static test apparatus was designed for and used in the evaluation. The test included some physiological-based parameters as well as some which exaggerated the expected actual use conditions. Both lubricated and nonlubricated condoms were tested. Before testing, however, most of the lubrication was removed from the lubricated condoms through rinsing with Dulbecco's phosphate-buffered saline and blotting with sterile paper towels. The 0X174 bacteriophage of 27 nm particle diameter, 32 nm including its bulky spikes, was used as the proxy challenge virus. Under test conditions, 12 of the latex condoms (2.6%) allowed some virus penetration of median quantity 0.0007 ml. Just two of the latex condoms were responsible for 99.8% of the total penetration among latex condoms overall. The performance of lubricated condoms was similar to that of nonlubricated ones. Four of the polyurethane condoms allowed penetration, but only one condom was responsible for 98.6% of total penetration. The difference in performance between latex and polyurethane condoms is not statistically significant. The median amount of penetration for latex condoms when extrapolated to expected actual use conditions was 0.00001 ml of semen. Therefore, even for the few condoms which allow virus penetration, the typical level of exposure to semen is several orders of magnitude lower than the amount of exposure expected when not using a condom.

Health risk assessment practices in the U.S. Food and Drug Administration.

The U.S. Food and Drug Administration (FDA) regulates a wide variety of consumer products. Safety issues involve chemical and microbial contaminants in food, biologies, and medical devices; side effects from prescription and nonprescription drugs; residues of animal drugs in food; and radiation from electronic devices. Because of this wide diversity, the legal standards, rules, and policies governing the regulation of these products differ considerably. Hence, risk assessment and risk management practices within the FDA are of necessity quite diverse. This paper presents a summary of risk assessment practices at each of the product centers of the FDA (Center for Food Safety and Applied Nutrition, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiological Health, and Center for Veterinary Medicine) and of the development of risk assessment procedures at the National Center for Toxicological Research.

An estimation of squamous cell carcinoma risk from ultraviolet radiation emitted by fluorescent lamps.

The risk of squamous cell carcinoma (SCC) from ultraviolet radiation (UV) emitted by unfiltered fluorescent lamps was assessed. The assessment employed a mathematical power model based on human epidemiological data, which relates the SCC incidence in the United States white population to ambient solar UV. The annual numbers of new SCC on anatomical sites chronically exposed to solar UV (head/face/neck and hands) were estimated for indoor workers. Then the number of SCC that may be caused by additional UV exposure from indoor fluorescent lighting was estimated: the lifetime exposure of indoor workers to typical fluorescent lighting (if unfiltered) may add 3.9% (1.6-12%) to the risk from solar UV, resulting in the induction of an additional 1500 (600-4500) SCC per annum in the United States. This calculated projection must be compared with the 110,000 SCC caused by solar exposure. Thus, this analysis suggests there may be a small increased risk of SCC from exposure to UV-emitting fluorescent lamps.

A simple method to test condoms for penetration by viruses.

A method by which virus penetration through condoms can be tested with simple, inexpensive equipment is described. The method uses chi X174 bacteriophage as the challenge virus and physiologically relevant pressure. Penetration by 0.1 microliters (or less) of challenge suspension can be readily detected. As examples, latex and natural-membrane condoms were examined.

Filtration sizes of human immunodeficiency virus type 1 and surrogate viruses used to test barrier materials.

Filters with well-defined holes were used to determine the effective diameters in buffer of human immunodeficiency virus type 1, herpes simplex virus type 1, and four bacteriophages (phi X174, T7, PRD1, and phi 6), which may serve as surrogate viruses for testing barrier materials. Bacteriophages phi 6 and PRD1 most closely model human immunodeficiency virus type 1 in filtration size.

Important factors for testing barrier materials with surrogate viruses.

This study evaluated bacteriophages phi X174, T7, PRD1, and phi 6 as possible surrogates for pathogenic human viruses to challenge barrier materials and demonstrated some important factors for their use. Chemical incompatibility with test material was demonstrated when lipid-enveloped phi 6 was inactivated by an aqueous eluate of vinyl gloves, but 0.5% calf serum protected phi 6 from the eluate. Low concentrations (2%) of calf serum also prevented the exaggerated binding of the bacteriophages to filters. Recovery of viruses from surfaces decreased with increasing time before recovery. Penetration through punctures displayed different types of kinetics. The combined data indicate that (i) some bacteriophages may serve as surrogate viruses, (ii) experimental conditions determine whether a particular virus is appropriate as a challenge, and (iii) phi X174 is an excellent choice as a surrogate virus to test barrier materials. The data further indicate that before barrier materials are challenged with viruses, adequate tests should be performed to ensure that the virus is compatible with the test material and test conditions, so that meaningful data will result.

Leakage of virus through used vinyl and latex examination gloves.

A total of 480 examination gloves (240 vinyl and 240 latex) were stressed by using manipulations designed to mimic patient care. At the highest use level, 38 (63%) of 60 vinyl gloves leaked bacteriophage phi X174 compared with 4 (7%) of 60 latex gloves. At lower use levels, there was no statistically significant difference in leakage.

Virus leakage through natural membrane condoms.

The authors determined virus leakage from condoms made from processed sheep caecum using two viral probes simultaneously. They poured a mixture of two viruses, the bacteriophage, phi X174 (4 X 10(7) pfu/ml), and the human pathogen, herpes simplex virus (about 1 X 10(6) pfu/ml), in a buffered solution into condoms, which were suspended into beakers also containing buffered solution. The authors then assayed aliquots from the beakers to measure the extent of virus leakage from the condoms. With one brand of condom, 10 out of 24 samples leaked small amounts of phi X174; with the other brand of condom, 13 out of 24 samples gave similar leakage. The extent of leakage varied over two orders of magnitude from condom to condom within each brand. Of the 23 condoms that leaked the smaller virus, phi X174 (27 nm in diameter), only two also leaked the larger herpesvirus (120-150 nm in diameter). These data demonstrate that (1) large and small viruses can leak from natural membrane condoms; (2) there is considerable variation from condom to condom in allowing leakage of the viruses; and (3) leakage of a small virus does not necessarily indicate that a larger virus will leak from that particular condom. The authors explain some inconsistencies in the published literature.

PIP: 24 natural membrane condoms of 2 brand were tested in a static bath for leakage of a small virus, PhiX174, 27 nm in diameter, and a larger virus, Herpes Simplex Virus Type I, 120-150 nm in diameter, in a 4-hour experiment. These viruses were chosen because the bacteriophage PhiX174 is slightly smaller than Hepatitis B and is easy and safe to assay, and Herpes virus is close in size and chemical composition to HIV, and is relatively easy to assay on mouse kidney cells. For the test 40 million plaque forming units (pfu/ml of PhiX174 and 1 million herpes simplex pfu/ml were incubated in a condom suspended in a beaker containing Dulbecco's phosphate buffer, with magnetic stirring. 10 to 24 condoms of Brand A and 13 of 24 Brand B leaked some phage. 2 condoms leaked some herpes virus. The results were computed into an index of barrier function, the barrier ratio. There was a variation in leakage over 2 orders of magnitude between condoms. The results in this status situation were similar to those obtained by others in a simulated active coitus experiment, in that greater amounts of the smaller viruses leaked through natural condoms.