Re‐evaluation of neohesperidine dihydrochalcone (E 959) as a food additive

Abstract

The present opinion deals with the re‐evaluation of neohesperidine dihydrochalcone (E 959) when used as a food additive. It is obtained by catalytic hydrogenation of a flavanone – neohesperidine – which is naturally occurring and thus isolated by alcohol extraction in bitter oranges (Citrus aurantium). Based on in vivo data in rat, neohesperidine dihydrochalcone is likely to be absorbed, also in humans, and to become systemically available. It does not raise a concern regarding genotoxicity. The toxicity data set consisted of studies on subchronic and prenatal developmental toxicity. No human studies were available. The data set was considered sufficient to derive a new acceptable daily intake (ADI). Based on the weight of evidence (WoE) analysis, the Panel considered unlikely that neohesperidine dihydrochalcone would lead to adverse effects on health in animals in the dose ranges tested. The Panel also considered that a carcinogenicity study was not warranted and that the lack of human data did not affect the overall confidence in the body of evidence. The Panel derived an ADI of 20 mg/kg bodyweight (bw) per day based on a no observed adverse effect level (NOAEL) of 4,000 mg/kg bw per day from a 13‐week study in rat, applying the standard default factors of 100 for inter‐ and intraspecies differences and of 2 for extrapolation from subchronic to chronic exposure. For the refined brand‐loyal exposure assessment scenario, considered to be the most appropriate for the risk assessment, the exposure estimates at the mean ranged from < 0.01 to 0.09 mg/kg bw per day and at the 95th percentile (P95) from 0.01 to 0.24 mg/kg bw per day. Considering the derived ADI of 20 mg/kg bw per day, the exposure estimates were below the reference value in all age groups. Therefore, the Panel concluded that dietary exposure to the food additive neohesperidine dihydrochalcone (E 959) at the reported uses and use levels would not raise a safety concern.

Neohesperidin Dihydrochalcone Ameliorates Experimental Colitis via Anti-Inflammatory, Antioxidative, and Antiapoptosis Effects

“…NHDC is a seminatural sweetener that is synthesized from the citrus flavonoid neohesperidin. , In 2022, the EFSA Panel transmitted a re-evaluation of NHDC (E 959) as a food additive, which suggested a derived acceptable daily intake (ADI) of 20 mg/kg bw per day and determined that NHDC is safe in terms of genotoxicity . Additionally, NHDC is considered safe for consumption by the US Food and Drug Administration .…”

“…Additionally, NHDC is considered safe for consumption by the US Food and Drug Administration . Unabsorbed NHDC is catabolized by the intestinal microbiota into dihydrocaffeic acid, and absorbed NHDC and its metabolites become systemically useable. , We selected the NHDC dose based on previous investigations in which NHDC was used at 100–200 mg/kg b.w. ,, …”

“…40 Unabsorbed NHDC is catabolized by the intestinal microbiota into dihydrocaffeic acid, and absorbed NHDC and its metabolites become systemically useable. 27,39 We selected the NHDC dose based on previous investigations in which NHDC was used at 100−200 mg/kg b.w. 22,24,28 NF-κB is a major transcriptional regulator that induces the expression of many molecules regarding UC, commands the expression of pro-inflammatory cytokines such as IL-1β, TNFα, IL-6, and IL-8 and protective molecules such as COX-2, β defensins, peroxisome proliferative-activated receptor γ (PPARγ), and IκBα that prevent inflammatory responses, and increases cells' survival by inducing antiapoptotic genes.…”

Novel foods, food enzymes, and food additives derived from food by-products of plant or animal origin: principles and overview of the EFSA safety assessment

“…Regarding FA, outputs of four different FA derived from by-products of plant origin re-evaluated by EFSA were retrieved, referring to tartaric acid (E 334) (tartar, lees, and grape marc of wine and/or grape pomace), vegetable carbon (E 153) (peat, wood, cellulose residues, coconut shells, or other shells), soybean hemicellulose (E 426) (okara -soybean fiber), and neohesperidine dihydrochalcone (E 959) (peels of bitter orange grapefruit) (38)(39)(40)(41).…”

“…The sweetener neohesperidine dihydrochalcone (E 959) may contain impurities, which are degradation products, compounds naturally occurring in the raw materials, or products of side reactions, all closely structurally related to neohesperidine dihydrochalcone. A Q(SAR) analysis by the OECD Q(SAR) Toolbox on the impurities contained in E 959 was performed, indicating no relevant differences between the structural alert profile of E 959 and its impurities and, after assessment, E 959 did not raise genotoxicity concerns ( 41 ).…”