Sanitation systems that systematically recover and reuse waste can promote social enterprise, reduce discharge of harmful nutrients, pathogens and other contaminants to the environment, replace synthetic fertilizer sources, and increase access to sanitation for improved human health. However, one significant obstacle towards successfully modernizing sanitation practices is the need to assure human health safety in the production and application of waste-derived products. This is especially important in resource-poor settings, where an added challenge to safe waste reuse is limited financial capacity for technology implementation. This project seeks to identify and reduce human and environmental health risks in the collection of urine and its processing into a fertilizer (struvite) in a large decentralized sanitation system in Durban, South Africa, where a network of over 80,000 urine-diverting dry toilets (UDDTs) is in place. A screening of fecal pathogens in source-separated urine was conducted to assess microbial health hazards. Rotavirus, Adenovirus and Shigella spp. were identified as the most frequently occurring pathogens. Occupational exposure to Rotavirus in urine via surface-to-hand followed by hand-to-mouth transfer was then evaluated to quantify the relative microbial health risks associated with urine collection and fertilizer production. The microlevel activity time series (MLATS) method was selected for the exposure assessment. First person videography of urine collection and processing was coded into high-resolution data yielding the frequency, duration, and chronology of contacts between each study participant hand and each surface. Additionally, a tracer exposure study was conducted to measure the volume of urine contacted by study participants. A model was constructed using this data to simulate the concentrations expected of pathogens on worker hands and potential dose of pathogens ingested from intermittent hand-to-mouth contacts. Study participants contacted visibly wet, presumably urine-contaminated surfaces more frequently during the production of struvite than during the collection of urine (e.g., 10 vs. 3 wet-surface contacts/hr). The tracer study revealed that during the production of struvite, study participant gloves contacted 0.04 – 50 ml urine per batch of struvite produced. Nevertheless, the probability of Rotavirus infection associated with single dose events from presumed hand-to-mouth contacts was somewhat low during struvite production (e.g., median P(response) [ 95% CI] = 1.5×10-4 [1.4×10-5 , 5.4×10-4] per dose for 10K simulations). This exposure may be unacceptable if urine collection and fertilizer production system is conducted at scale or if multiple hand-to-mouth contacts occur during urine handling. In the context of resource reuse, source-separated urine is often falsely considered “sterile” or nearly so. Urine treatment via storage can reduce pathogen concentrations in struvite reactor influent to reduce exposure. Fertilizer production techniques that reduce human contact with urine during processing such as automated reactors should be favored. This study is unique in its approach to accurately model the time-dependent concentration of pathogens on hands due to urine contamination and to quantify the consequent exposure potential using videography, fecal contamination analysis in urine and on surfaces and a tracer study. Quantitatively identifying risks in this way is an important strategy for identifying and overcoming barriers to safe and sustainable sanitation.