Vitami 2001). Symptoms of acute toxicity include: increased cerebrospinal fluid pres sure, bulging fontanelle in infants, headache and blurred vision in adolescents and adults, loss of appetite, nausea, vomiting lassitude and abdominal pain. An acceptable dose for mothers is 400000IU vitamin A(120mg retinyl palmitate i. e. 11U=0.3ug retinol) post partum while 500001U is assumed safe for 0-6 month infants. 100000IU for infants >6 months and 200000lu for those >12 months old. however in infants and children 25000-500001U occasion- ally leads to bulging fontanel. In about 6% of infants 3000001U can lead to nausea and vomiting and to diarrhoea in about 16% and although this is transient, it is unacceptable (IoM, 2001) Retinyl esters in plasma are indicators of high or recent vitamin A intake i.e they transiently increase after a vitamin A-rich meal, 1-2 X RNI and particularly with supplementation. Plasma retinoic acid will also go up after eating liver or aking high doses of vitamin A, and in lactating women the retinoic acid may go into the breast milk although this has not been measured. Breast milk retinyl palmitate is a useful indicator to monitor total maternal vitamin A intake, that is milk retinol concentration will be very similar to plasma retinol. There is no evidence of an upper concentration of breast milk vitamin A that is harmful to infants Chronic toxicity from retinol Definitions of upper limits of toxicity (IOM, 2001) No observed adverse effect level (NoAEl) or the highest dose which has no adverse effect Tolerable upper intake level (UL) is the highest level of intake likely to pose no risk for almost all members of the population, where UL NOAEL/uncertainty factor(UF) Chronic hypervitaminosis A can be defined as any symptom resulting from continued ingestion of high doses of vitamin A for months or years(Blomhoff, 2001). In adults, there are many reports of chronic toxicity where the intake of vitamin A exceeds 15 mg/d, characterised by headache, fatigue, anorexia, itch skin, liver damage, desquamation of mucous membranes and of skin The NOAEL for adults is set 15 mg/d and the UL is 3 mg/d, where the UF 5 because of severe irreversible effect and inter-individual variability in sensi- tivity. If the UL was <3 mg, 50%o of adults in the US would exceed the UL, yet few cases of liver toxicity are seen. The mean normal US liver concentration is 100ug/g(range 10-1400ug/g) In infants and young children toxicity produces bulging fontanelle. The NOAEL is 6mg/d and the ul is 0.6mg/d, where the uF= 10 because of uncer- ainty and inter-individual variability in sensitivity In women of child-bearing age, toxicity can lead to teratogenicity, therefore the NOaEl is set at 4.5 mg and the Ul at 3 mg/d(10000IU). The most serious effects of vitamin A toxicity include foetal resorption, birth defects, abortion and permanent learning difficulties in the offspring (IOM, 2001)(see section2001). Symptoms of acute toxicity include: increased cerebrospinal fluid pres￾sure, bulging fontanelle in infants, headache and blurred vision in adolescents and adults, loss of appetite, nausea, vomiting lassitude and abdominal pain. An acceptable dose for mothers is 400 000 IU vitamin A (120 mg retinyl palmitate i.e. 1 IU = 0.3mg retinol) post partum while 50 000 IU is assumed safe for 0–6 month infants, 100 000 IU for infants > 6 months and 200 000 IU for those > 12 months old. However, in infants and children 25 000–50 000 IU occasion￾ally leads to bulging fontanel. In about 6% of infants 300 000 IU can lead to nausea and vomiting and to diarrhoea in about 16% and although this is transient, it is unacceptable (IOM, 2001). Retinyl esters in plasma are indicators of high or recent vitamin A intake i.e. they transiently increase after a vitamin A-rich meal, 1–2 ¥ RNI and particularly with supplementation. Plasma retinoic acid will also go up after eating liver or taking high doses of vitamin A, and in lactating women the retinoic acid may go into the breast milk although this has not been measured. Breast milk retinyl palmitate is a useful indicator to monitor total maternal vitamin A intake, that is, milk retinol concentration will be very similar to plasma retinol. There is no evidence of an upper concentration of breast milk vitamin A that is harmful to infants. Chronic toxicity from retinol Definitions of upper limits of toxicity (IOM, 2001) No observed adverse effect level (NOAEL) or the highest dose which has no adverse effect. Tolerable upper intake level (UL) is the highest level of intake that is likely to pose no risk for almost all members of the population, where UL = NOAEL/uncertainty factor (UF). Chronic hypervitaminosis A can be defined as any symptom resulting from continued ingestion of high doses of vitamin A for months or years (Blomhoff, 2001). In adults, there are many reports of chronic toxicity where the intake of vitamin A exceeds 15 mg/d, characterised by headache, fatigue, anorexia, itchy skin, liver damage, desquamation of mucous membranes and of skin. The NOAEL for adults is set 15 mg/d and the UL is 3 mg/d, where the UF = 5 because of severe irreversible effect and inter-individual variability in sensi￾tivity. If the UL was <3 mg, 50% of adults in the US would exceed the UL, yet few cases of liver toxicity are seen. The mean normal US liver concentration is 100mg/g (range 10–1400mg/g). In infants and young children toxicity produces bulging fontanelle. The NOAEL is 6 mg/d and the UL is 0.6 mg/d, where the UF = 10 because of uncer￾tainty and inter-individual variability in sensitivity. In women of child-bearing age, toxicity can lead to teratogenicity, therefore the NOAEL is set at 4.5 mg and the UL at 3 mg/d (10 000 IU). The most serious effects of vitamin A toxicity include foetal resorption, birth defects, abortion and permanent learning difficulties in the offspring (IOM, 2001) (see section 3.3.3). Vitamins 45