A 60-year-old male farmworker presents with a 1-year history of resting tremor, bradykinesia, and rigidity. He has worked for 25 years applying organophosphate pesticides. A retrospective cohort study assesses the relationship between duration of pesticide exposure and the development of Parkinsonian symptoms. Researchers report the following observations:

1. Pesticide exposure always preceded symptom onset by at least 5 years.
2. Individuals exposed for more than 20 years have a relative risk of 3.5 compared with those exposed for less than 5 years.
3. In animal models, organophosphates selectively induce dopaminergic neuronal death in the substantia nigra.
4. Similar associations have been observed in cohort studies from multiple countries.
5. Pesticide exposure is linked specifically to Parkinson’s disease and not to other neurodegenerative disorders.

Which observation most directly exemplifies the dose–response criterion in the Bradford Hill guidelines for establishing causation?