Scientific Documents
Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to di-Butylphthalate (DBP) for use in food contact materials
Question number: EFSA-Q-2003-192 Adopted: 23 June 2005
Summary 
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Opinion (0.2Mb)
Summary
The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) has been asked to re-evaluate di-butylphthalate (DBP) for use in the manufacture of food contact materials.
Previously, a temporary Tolerable Daily Intake (t-TDI) of 0.05 mg/kg bw was set by the Scientific Committee for Food (SCF), based on the endpoint of peroxisome proliferation in rodent liver. There is now a scientific consensus that liver peroxisome proliferation in rodents is not relevant for human risk assessment. The critical effects of DBP relate to reproduction. From the several studies available, the critical observations were as follows.
In a two-generation reproduction study in rats with a continuous breeding protocol and with exposure of both male and female animals, the lowest dose-level of 0.1 % in the diet (52 mg/kg bw/day for males and 80 mg/kg bw/day for females) appeared to be a Lowest Observed Adverse Effect Level (LOAEL), based on embryotoxic effects on pup weight and number of live pups per litter. These effects were seen in the absence of maternal toxicity. It should be noted that the LOAEL of 52 mg/ kg bw/day (0.1% in the diet) was derived from an extensive study utilising sensitive endpoints (such as sperm parameters, oestrous cycle characterization and detailed testicular histopathology).
In another reproduction study, a No Observed Adverse Effect Level (NOAEL) of 50 mg/kg bw/day and a LOAEL of 100 mg/kg bw/day for toxicity of DBP on male reproductive development in the F1 generation have been observed.
A recent developmental toxicity study in the rat, with dietary exposure to DBP during the period from late gestation (gestational day 15) to the end of lactation (postnatal day 21), has shown effects on the development of male and female offspring at lower doses than those found previously. Based on loss of germ cell development and mammary gland change at 20 mg/kg in the diet (the lowest tested dose), a NOAEL could not be established.
However, given the reversibility of the effects at all dose levels and especially at the lowest dose level (20 mg/kg feed, which corresponds to 1.5 to 3 mg/kg bw/day) and also given that in several reproductive toxicity studies with longer exposure periods approximately 30 -fold higher NOAELs or LOAELs have been determined, an uncertainty factor of 200, to derive a TDI for DBP based on the LOAEL of 20 mg/kg feed is considered sufficient.
According to the above statement, the Panel allocates a TDI for DBP of 0.01 mg/kg bw, based on a LOAEL of 2 mg/kg bw/day and making use of an uncertainty factor of 200.
The limited available data on DBP concentration in foods and diets in the UK and Denmark were used to provide an estimation of dietary exposure. In the UK, mean and high (97.5th percentile) intakes of DBP from dietary sources were estimated to be respectively 0.013 and 0.031 mg/person/day in the adult population (equivalent to 0.2 and 0.5 microg/kg bw/day) considering a 60 kg adult.
In a Danish study, DBP estimated mean exposure ranged from 0.13 to 0.29 mg/day, i.e. 1.8 to 4.1 microg/kg bw/day, considering a 70 kg adult. Based on the highest concentration of DBP determined, exposure at high percentiles was estimated as 0.72 mg/day equivalent to 10.2 microg/kg bw/day.
In a further Danish study, the main dietary sources of exposure were estimated to be root crops (83%) and leaf crops (13%). The total daily oral intake at the regional level (Denmark) was estimated to be 1.6 microg/kg bw/day in adults, 8 microg/kg bw/day in children aged 1 to 6 years, and 3.5 microg/kg bw/day in children aged 7 to 14 years.
Based on the detection limit, intake from infant formulae would be less than 16.4 microg/kg bw/day in infants of less than 6 months and 6.6 microg/kg bw/day in infants of more than 6 months. For infants of more than 6 months, ready-to-use baby foods were also taken into account and the exposure was therefore estimated as less than 7.9 microg/kg bw/day.
The Panel notes that exposure to DBP from food consumption is in the range of the TDI. There are, however, a number of other sources which contribute to the overall human exposure to DBP. The Panel recommends that improved estimates of exposure to DBP from all sources along with their relative importance should be provided in order to decide what proportion of the TDI can be allocated to food contact materials alone.
Published: 19 September 2005
Last updated: 16 November 2005
Last updated: 16 November 2005
