Update of the risk assessment of di‐butylphthalate (DBP), butyl‐benzyl‐phthalate (BBP), bis(2‐ethylhexyl)phthalate (DEHP), di‐isononylphthalate (DINP) and di‐isodecylphthalate (DIDP) for use in food contact materials

Abstract

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) was asked by the European Commission to update its 2005 risk assessments of di-butylphthalate (DBP), butylbenzyl-phthalate (BBP), bis(2-ethylhexyl)phthalate (DEHP), di-isononylphthalate (DINP) and diisodecylphthalate (DIDP), which are authorised for use in plastic food contact material (FCM). Dietary exposure estimates (mean and high (P95)) were obtained by combining literature occurrence data with consumption data from the EFSA Comprehensive Database. The highest exposure was found for DINP, ranging from 0.2 to 4.3 and from 0.4 to 7.0 lg/kg body weight (bw) per day for mean and high consumers, respectively. There was not enough information to draw conclusions on how much migration from plastic FCM contributes to dietary exposure to phthalates. The review of the toxicological data focused mainly on reproductive effects. The CEP Panel derived the same critical effects and individual tolerable daily intakes (TDIs) (mg/kg bw per day) as in 2005 for all the phthalates, i.e. reproductive effects for DBP (0.01), BBP (0.5), DEHP (0.05), and liver effects for DINP and DIDP (0.15 each). Based on a plausible common mechanism (i.e. reduction in fetal testosterone) underlying the reproductive effects of DEHP, DBP and BBP, the Panel considered it appropriate to establish a group-TDI for these phthalates, taking DEHP as index compound as a basis for introducing relative potency factors. The Panel noted that DINP also affected fetal testosterone levels at doses around threefold higher than liver effects and therefore considered it conservative to include it within the group-TDI which was established to be 50 lg/kg bw per day, expressed as DEHP equivalents. The aggregated dietary exposure for DBP, BBP, DEHP and DINP was estimated to be 0.9-7.2 and 1.6-11.7 lg/kg bw per day for mean and high consumers, respectively, thus contributing up to 23% of the group-TDI in the worst-case scenario. For DIDP, not included in the group-TDI, dietary exposure was estimated to be always below 0.1 lg/kg bw per day and therefore far below the TDI of 150 lg/kg bw per day. This assessment covers European consumers of any age, including the most sensitive groups. Based on the limited scope of the mandate and the uncertainties identified, the Panel considered that the current assessment of the five phthalates, individually and collectively, should be on a temporary basis. ):5838 related chronic hepatic and renal effects in rats was identified. An uncertainty factor of 100 was applied for deriving the TDI of 0.15 mg/kg bw per day for DINP.-For DIDP, a NOAEL of 15 mg DIDP/kg bw per day for liver effects in dogs wasidentified. An uncertainty factor of 100 was applied for deriving the TDI of 0.15 mg/kg bw per day for DIDP. 1 ECHA (2017a) used a factor of 3 (total UF 300) for the extrapolation from LOAEL to NAEL.The CEP Panel considers that the effect on the liver is still the most sensitive endpoint for these two phthalates. However, the possibility to establish HBGVs for re...

Exposure of Adult Female Mice to Low Doses of di(2-ethylhexyl) Phthalate Alone or in an Environmental Phthalate Mixture: Evaluation of Reproductive Behavior and Underlying Neural Mechanisms

“…The TDI dose of 50 lg=kg=d for DEHP was established by the EFSA 2005 on the basis of the ability of this molecule to reduce fetal testosterone production, whereas the oral reference dose of 20 lg=kg=d established by the U.S. Environmental Protection Agency in 1987 was determined for an increased liver weight (U.S. EPA 1987). A recent revision by the EFSA of five phthalates including DEHP maintains the TDI dose at 50 lg=kg=d according to effects on fetal testosterone production (EFSA 2019). Our studies at the neural level addressing adult exposure (Dombret et al 2017; and in the present study) and some studies concerning recent evidence reporting in vivo peripheral effects at doses equivalent or below the reference doses for prenatal (Abdel-Maksoud et al 2019;Barakat et al 2019) or adult exposure (Hannon et al 2014;Lu et al 2019) reveal the high sensitivity of both female and male reproductive systems.…”

“…However, the potential effects of adult exposure to DEHP on the neural regulation of reproductive behavior have received less attention. In this context, we previously showed that exposure of adult male mice to DEHP at the tolerable daily intake dose (TDI) of 50 lg=kg=d (EFSA 2005(EFSA , 2019 or at lower doses close to the environmental exposure altered courtship behavior (Dombret et al 2017). In particular, DEHP exposure lowered the emission of ultrasonic vocalizations (USVs) and the ability to attract females and delayed the initiation of mating.…”

Immuno-Hormonal, Genetic and Metabolic Profiling of Newborns as a Basis for the Life-Long OneHealth Medical Record: A Scoping Review

“…Many endocrine disrupting chemicals are considered to have a moderate to low bioaccumulating potential, however, exposure during a vulnerable susceptibility window can cause permanent effects. Example plasticisers such as several phthalates and bisphenol, which alter male reproductive development and mammary development, respectively, upon exposure in utero; these effects, observed in rodent studies, were considered relevant to human health by the European Food Safety Authority [ 40 , 41 ]. Transplacental exposures to endocrine disrupting chemicals at exposure levels found in the general population are associated with possible life-long impact on growth and development [ 11 , 12 , 34 ].…”

Acute Toxicity and DNA Instability Induced by Exposure to Low Doses of Triclosan and Phthalate DEHP, and Their Combinations, in vitro

“…Once absorbed, DEHP is quickly metabolized mainly in liver, resulting in several metabolites, such as the mono(2-ethylhexyl) phthalate (MEHP), which is associated with most of the toxic effects induced by DEHP exposure (Fay et al, 1999;Rusyn et al, 2006;Caldwell, 2012). Previous in vitro and in vivo studies also showed that DEHP can induce disturbances of cell homeostasis, leading to DNA instability, dysfunctions of the mitotic spindle, and cell death (Turner et al, 1974;Choi et al, 2010;Caldwell, 2012;Li et al, 2014;Rowdhwal and Chen, 2018;Silano et al, 2019).…”