The available studies cover the majority of endpoints considered relevant for assessment of reproductive effects and other toxicities and do not indicate the presence of effects on reproduction or development at doses lower than 50 mg/kg bw/day. The lowest NOAEL of 5 mg/kg bw/day derived in the recent two-generation reproductive toxicity study in mice is based on liver effects. Toxic effects of repeated administration of BPA on the liver in mice have also been observed in previous studies with a LOAEL of 120 mg/kg bw/day, suggesting that liver toxicity is at least as sensitive an endpoint for BPA as reproductive and developmental effects. The NOAEL for liver toxicity in mice is identical to the derived NOAEL for reproductive toxicity of bisphenol A in rats used in the EU RAR, which is based on effects on adult and offspring body weight gain. The Panel’s conclusions are based on the now available, extensive database on repeated-dose toxicity, reproductive and developmental toxicity of BPA in rodents and on the comparison of toxicokinetics in primates, including humans, and rodents. The Panel concluded that the new studies provide a basis for revising the uncertainty factors that were used by the SCF to derive the temporary TDI of 0.01 mg/kg bw in 2002. In particular, the Panel now considers that the database concerning reproduction and development has been considerably strengthened and that the additional uncertainty factor of 5, introduced by the SCF in 2002 for the uncertainties in the database on production and development, is no longer required. The Panel also concluded, in view of the well described species differences in toxicokinetics, howing a low level of free BPA in humans compared with rats, that a default uncertainty factor of 100 applied to the overall NOAEL from the rodent studies can be considered as conservative. The Panel therefore established a full TDI of 0.05 mg BPA/kg bw, derived by applying a 100-fold uncertainty factor to the overall NOAEL of 5 mg/kg bw/day. Dietary exposure assessments on BPA have been made by the Panel for adults, infants and children. The estimates of potential dietary exposure to BPA in infants took account of breast feeding, feeding formula using PC bottles and consumption of commercial foods and beverages. The resulting exposure assessments ranged from 0.2 microg/kg bw/day in 3–month-old breastfed infants up to 13 microg/kg bw/day in 6-12–month-old infants. These estimates were based on conservative migration values of BPA and the 95th percentiles of consumption. The estimates of potential dietary exposure in young children and adults were respectively 5.3 and 1.5 microg/kg bw/day based on conservative migration values of BPA and conservative estimates of consumption of commercial foods and beverages. The Panel noted that the conservative estimates of exposure were less than 30% of the TDI in all population groups considered. These exposure estimates include BPA migration into canned foods and into food in contact with PC table ware or storage receptacles. On the other hand, they do not include either potential migration of BPA from receptacles into food during Bisphenol A for use in food contact materials The EFSA Journal (2006) 428, p. 6 of 75 microwave heating or potential migration of BPA into drinking water due to the use of PC and of epoxy-phenolic resins in water pipes and in water storage tanks. Information on potential migration of BPA from these sources would be useful.

Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to 2,2-BIS(4-HYDROXYPHENYL)PROPANE (Bisphenol A)

GRILLI, SANDRO;
2007

Abstract

The available studies cover the majority of endpoints considered relevant for assessment of reproductive effects and other toxicities and do not indicate the presence of effects on reproduction or development at doses lower than 50 mg/kg bw/day. The lowest NOAEL of 5 mg/kg bw/day derived in the recent two-generation reproductive toxicity study in mice is based on liver effects. Toxic effects of repeated administration of BPA on the liver in mice have also been observed in previous studies with a LOAEL of 120 mg/kg bw/day, suggesting that liver toxicity is at least as sensitive an endpoint for BPA as reproductive and developmental effects. The NOAEL for liver toxicity in mice is identical to the derived NOAEL for reproductive toxicity of bisphenol A in rats used in the EU RAR, which is based on effects on adult and offspring body weight gain. The Panel’s conclusions are based on the now available, extensive database on repeated-dose toxicity, reproductive and developmental toxicity of BPA in rodents and on the comparison of toxicokinetics in primates, including humans, and rodents. The Panel concluded that the new studies provide a basis for revising the uncertainty factors that were used by the SCF to derive the temporary TDI of 0.01 mg/kg bw in 2002. In particular, the Panel now considers that the database concerning reproduction and development has been considerably strengthened and that the additional uncertainty factor of 5, introduced by the SCF in 2002 for the uncertainties in the database on production and development, is no longer required. The Panel also concluded, in view of the well described species differences in toxicokinetics, howing a low level of free BPA in humans compared with rats, that a default uncertainty factor of 100 applied to the overall NOAEL from the rodent studies can be considered as conservative. The Panel therefore established a full TDI of 0.05 mg BPA/kg bw, derived by applying a 100-fold uncertainty factor to the overall NOAEL of 5 mg/kg bw/day. Dietary exposure assessments on BPA have been made by the Panel for adults, infants and children. The estimates of potential dietary exposure to BPA in infants took account of breast feeding, feeding formula using PC bottles and consumption of commercial foods and beverages. The resulting exposure assessments ranged from 0.2 microg/kg bw/day in 3–month-old breastfed infants up to 13 microg/kg bw/day in 6-12–month-old infants. These estimates were based on conservative migration values of BPA and the 95th percentiles of consumption. The estimates of potential dietary exposure in young children and adults were respectively 5.3 and 1.5 microg/kg bw/day based on conservative migration values of BPA and conservative estimates of consumption of commercial foods and beverages. The Panel noted that the conservative estimates of exposure were less than 30% of the TDI in all population groups considered. These exposure estimates include BPA migration into canned foods and into food in contact with PC table ware or storage receptacles. On the other hand, they do not include either potential migration of BPA from receptacles into food during Bisphenol A for use in food contact materials The EFSA Journal (2006) 428, p. 6 of 75 microwave heating or potential migration of BPA into drinking water due to the use of PC and of epoxy-phenolic resins in water pipes and in water storage tanks. Information on potential migration of BPA from these sources would be useful.
F. Aguilar; H. Autrup; S. Barlow; L. Castle; R. Crebelli; W. Dekant; K.-H. Engel; N. Gontard; D. Gott; S. Grilli; R. Gürtler; J. C. Larsen; J.-C. Leblanc; C. Leclercq; F. X. Malcata; W. Mennes; M. R. Milana; I. Pratt; I. Rietjens; P. Tobback; F. Toldrá.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/89984
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