4-Nitrophenol mentioned in ‘Scientific Opinion on the re‐evaluation of aspartame (E 951) as a food additive’ (2013)

3.2.6.2. Studies on the effect of aspartame administration on xenobiotic metabolising enzymes
An early study (E15, 1972) indicated that the oral administration of aspartame to male Charles River rats (2000-4000 mg/kg) for four days had no acute effect on hepatic cytochrome P450 (CYP)-
mediated xenobiotic metabolism, as measured as aminopyrine N-demethylation, p-nitroanisole Ndemethylation, hexobarbital sleeping time or zoxazolamine paralysis time. Two studies subsequently showed that aspartame administration (≤ 4000 mg/kg bw/day for up to 90 days) had small effects on hepatic Phase 1 and Phase 2 metabolism in rodents after 45 days treatment but not after 90 days treatment (Tutelyan et al., 1990). In a more recent study (Vences-Mejia et al., 2006), male Wistar rats were dosed with aspartame (75 or 125 mg/kg bw/day) daily for 30 days. Using hepatic microsomal samples from liver, cerebrum (pooled) and cerebellum (pooled), the authors investigated CYPs by immunoblotting (CYPs 1A1, 1A2, 2B, 3A2 and 2E1) and enzymatic activity measurement (ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, pentoxyresorufin O-depentylase, benzyloxyresorufin O-debenzylase, 4-nitrophenol hydroxylase and erythromycin-N-demethylase). No effect of aspartame treatment was observed in the liver samples. However, bands corresponding to CYPs 1A1, 1A2, 2B, 3A2 were detectable in the cerebrum and cerebellum samples brain samples after aspartame treatment (but not in the control samples) and increases in all the enzyme activities were reported. The Panel noted that the findings have minimal relevance for human risk assessment.

https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2013.3496