Background: The World Health Organization (WHO) has set out a stringent procedure to ensure that guidelines contain evidence-based recommendations for healthcare interventions. WHO also expects exposure guidelines for various environmental risk factors to be evidence based. However, applying the same methods to exposure guidelines as for intervention guidelines poses many challenges.

Objectives: To list the challenges encountered in the development of WHO guidelines for environmental and occupational exposures.

Methods: Our experience with developing WHO guidelines on noise, air-pollution, nanomaterials and radiofrequency fields.

Results: We encountered the following challenges.
For systematic reviews of health risks of exposures:
1. PICO questions for systematic reviews should be transformed, for example, into Participants, Exposures, Comparison exposures, Confounders and Study designs (PECCOS).
2. For environmental risks it is unrealistic to review the evidence for every possible health outcome.
3. There are no well-established methods for systematic reviews of health risks of exposures. In particular, the establishment of a dose-response curve is technically complicated.
4. There is only limited experience with systematic risk-of-bias assessment for environmental studies.
5. The assessment of the quality of the body of evidence as developed by GRADE is not applicable to exposure studies, and content experts feel that it unfairly downgrades the environmental evidence.

For evidence-to-recommendation frameworks:
1. There are no established methods to determine an ‘acceptable’ exposure level below which the risks of adverse health effects would be acceptable.
2. There is no generally accepted definition for a guideline threshold level.
3. WHO environmental guidelines have so far not aimed to make recommendations on interventions but decision making is about the best intervention to solve a problem. Content experts see this as risk management which is outside their scientific remit and context specific.

Conclusions: Considerable challenges remain for WHO environmental health guideline development.