Comments on Dakeishi M, Murata K, Grandjean P. 2006. Long-term consequences of arsenic poisoning during infancy due to contaminated milk powder. Environ Health 5(1):31;
Marie Vahter, Karolinska Institutet
8 November 2006
Dear Editor,
We read with great interest the recent article by Dakeishi and co-authors concerning the unfortunate arsenic poisoning, including more than 100 deaths, that occurred among Japanese infants in 1955-1956 (Dakeishi et al. 2006). The article reviews the acute and late effects of the incident and points out the need for more information on the effects of arsenic on the central nervous system, in particular during development. The source of arsenic in the poisoning incident was contaminated milk powder, produced by the Morinaga company. The milk powder was used to prepare milk for bottle-fed infants during a few months time, until a number of severe poisoning cases could be linked to the milk. It was estimated that the prepared milk contained 4-7 mg/L, resulting in daily doses to the infants of slightly above 500 µg/Kg body weight. Clinical poisoning occurred after a few weeks of exposure, corresponding to a total dose of 60 mg arsenic. The article reviews the follow-up studies carried out when the children were about 14 years, revealing late effects, and in particular neurological disorders.
The authors are critical to the fact that this information has been ignored by scientists and international agencies, which is largely true. However, the earlier WHO/IPCS Environmental Health Criteria on arsenic (WHO/IPCS 1981) did review the Morinaga milk poisoning event, based on the Japanese publications (Hamamoto 1955; Nakagawa and Iibuchi 1970). It was estimated that the infants ingested 1.3 to 3.6 mg of arsenic daily, and that 130 deaths were reported. The IPCS document also referred to the follow-up studies conducted in the early 1970ies (Ohira and Aoyama 1972; Yamashita et al. 1972), which reported increased prevalence of hearing loss and brain wave abnormalities. These data formed the basis for the risk assessment of short-term exposure to arsenic; concluding that ingestion of 3 mg of inorganic arsenic per day, over a period of a few weeks, may give rise to severe poisoning in infants. Also, follow-up studies of the neurological effects were recommended. In Sweden, the IPCS/WHO risk estimation has been used in the assessment of health risks associated with contaminated soil, especially in areas where wood preservation plants have been operating.
Dakeishi and co-authors also claim that the main recent risk assessment documents, published by the World Health Organization (WHO 2001) and US National Academy of Sciences (NRC 1999), have not offered a single sentence to developmental neurotoxicity. It should be noted that the risk assessment document of the US National Academy of Sciences (NRC 1999), as well as the update (NRC 2001) did include chapters on neurological as well as reproductive and developmental effects, reviewing both human and animal data. It was concluded that some studies show an association between arsenic exposure and adverse pregnancy outcome, but that data were inadequate to draw firm conclusions. The updated document published in 2001 reviewed two additional studies focusing on subtle cognitive effects following chronic arsenic exposure (Calderon et al. 2001; Siripitayakunkit et al. 1999).
Since that, a few more articles indicating neurodevelopmental effects of arsenic have been published (Tsai et al. 2003; Wasserman et al. 2006; Wasserman et al. 2004; Watanabe et al. 2003), although the effect estimates are not conclusive, due to limitations in exposure assessments and/or considerations of potential confounding. Considering the fact that millions of families word-wide use drinking water with elevated arsenic concentrations (IARC 2004; Vahter et al. 2006), there is indeed a need for more information on arsenic induced neurotoxicity following early-life exposure. Because of human and experimental studies have demonstrated that arsenic is easily transferred to the fetus (Concha et al. 1998). Thus, effects on child development may result from both pre- and postnatal exposure to arsenic. Therefore, it is highly appreciated that an update and reminder of the tragic poisoning incident is published in a scientific journal, in particular considering the lack of data on effects of early-life exposure to arsenic.
Calderon J, Navarro ME, Jimenez-Capdeville ME, Santos-Diaz MA, Golden A, Rodriguez-Leyva I, et al. 2001. Exposure to arsenic and lead and neuropsychological development in Mexican children. Environ Res 85(2):69-76.
Concha G, Vogler G, Nermell B, Vahter M. 1998. Low-level arsenic excretion in breast milk of native Andean women exposed to high levels of arsenic in the drinking water. Int Arch Occup Environ Health 71(1):42-46.
Dakeishi M, Murata K, Grandjean P. 2006. Long-term consequences of arsenic poisoning during infancy due to contaminated milk powder. Environ Health 5(1):31.
Hamamoto E. 1955. Infant arsenic poisoning by powdered milk. . Nihon Iji Shimpo(No. 1649):3-12 (In Japanese).
IARC. 2004. Volume 84. Some drinking-water disinfectants and Contaminants, including arsenic. Lyon:International Agency for Research on Cancer.
Nakagawa Y, Iibuchi Y. 1970. On the follow-up investigation of Morinaga milk arsenic poisoning. . Igaku no Ayumi 74:1-3.
NRC. 1999. Arsenic in drinking water. Washington, D.C.:National Academy Press.
---. 2001. Arsenic in drinking water: 2001 update. Washington, D.C.:National Academy Press.
Ohira M, Aoyama H. 1972. Epidemiological studies on the Morinaga powdered milk poisoning incident. . PJpn J Hyg 27:500-531.
Siripitayakunkit P, Visudhiphan M, Pradipasen M, Vorapongsathron T. 1999. Association between chronic arsenic exposure and children's intelligence in Thailand.
. In: Arsenic exposure and health effects (Chappell WR, Abernathy CO, R.L. C, eds). New York:Elsevier, 141-150.
Tsai SY, Chou HY, The HW, Chen CM, Chen CJ. 2003. The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence. Neurotoxicology 24(4-5):747-753.
Vahter ME, Li L, Nermell B, Rahman A, El Arifeen S, Rahman M, et al. 2006. Arsenic Exposure in Pregnancy: A Population-based Study in Matlab, Bangladesh Journal of Health, Population and Nutrition 24(2):236-245.
Wasserman GA, Liu X, Parvez F, Ahsan H, Factor-Litvak P, Kline J, et al. 2006. Water Arsenic Exposure and Intellectual Function in Six-Year-Old Children in Araihazar, Bangladesh.
. Environ Health Perspect doi:10.1289/ehp.9501 available via http://dx.doi.org/ [Online 18 October 2006]
Wasserman GA, Liu X, Parvez F, Ahsan H, Factor-Litvak P, van Geen A, et al. 2004. Water arsenic exposure and children's intellectual function in Araihazar, Bangladesh. Environ Health Perspect 112(13):1329-1333.
Watanabe C, Inaoka T, Matsui T, Ishigaki K, Murayama N, Ohtsuka R. 2003. Effects of arsenic on younger generations. J Environ Sci Health A Tox Hazard Subst Environ Eng 38(1):129-139.
WHO. 2001. EHC 224, Arsenic and Arsenic Compounds.
WHO/IPCS. 1981. Environmental Health Criteria 18, Arsenic Geneva:World Health Organization
Yamashita N, Doi M, Nishio M, Hojo H, Tanaka M. 1972. [Recent observations of Kyoto children poisoned by arsenic tainted "Morinaga Dry Milk" (author's transl)]. Nippon Eiseigaku Zasshi 27(4):364-399.
Environmental Health
Comments on Dakeishi M, Murata K, Grandjean P. 2006. Long-term consequences of arsenic poisoning during infancy due to contaminated milk powder. Environ Health 5(1):31;
8 November 2006
Dear Editor,
We read with great interest the recent article by Dakeishi and co-authors concerning the unfortunate arsenic poisoning, including more than 100 deaths, that occurred among Japanese infants in 1955-1956 (Dakeishi et al. 2006). The article reviews the acute and late effects of the incident and points out the need for more information on the effects of arsenic on the central nervous system, in particular during development. The source of arsenic in the poisoning incident was contaminated milk powder, produced by the Morinaga company. The milk powder was used to prepare milk for bottle-fed infants during a few months time, until a number of severe poisoning cases could be linked to the milk. It was estimated that the prepared milk contained 4-7 mg/L, resulting in daily doses to the infants of slightly above 500 µg/Kg body weight. Clinical poisoning occurred after a few weeks of exposure, corresponding to a total dose of 60 mg arsenic. The article reviews the follow-up studies carried out when the children were about 14 years, revealing late effects, and in particular neurological disorders.
The authors are critical to the fact that this information has been ignored by scientists and international agencies, which is largely true. However, the earlier WHO/IPCS Environmental Health Criteria on arsenic (WHO/IPCS 1981) did review the Morinaga milk poisoning event, based on the Japanese publications (Hamamoto 1955; Nakagawa and Iibuchi 1970). It was estimated that the infants ingested 1.3 to 3.6 mg of arsenic daily, and that 130 deaths were reported. The IPCS document also referred to the follow-up studies conducted in the early 1970ies (Ohira and Aoyama 1972; Yamashita et al. 1972), which reported increased prevalence of hearing loss and brain wave abnormalities. These data formed the basis for the risk assessment of short-term exposure to arsenic; concluding that ingestion of 3 mg of inorganic arsenic per day, over a period of a few weeks, may give rise to severe poisoning in infants. Also, follow-up studies of the neurological effects were recommended. In Sweden, the IPCS/WHO risk estimation has been used in the assessment of health risks associated with contaminated soil, especially in areas where wood preservation plants have been operating.
Dakeishi and co-authors also claim that the main recent risk assessment documents, published by the World Health Organization (WHO 2001) and US National Academy of Sciences (NRC 1999), have not offered a single sentence to developmental neurotoxicity. It should be noted that the risk assessment document of the US National Academy of Sciences (NRC 1999), as well as the update (NRC 2001) did include chapters on neurological as well as reproductive and developmental effects, reviewing both human and animal data. It was concluded that some studies show an association between arsenic exposure and adverse pregnancy outcome, but that data were inadequate to draw firm conclusions. The updated document published in 2001 reviewed two additional studies focusing on subtle cognitive effects following chronic arsenic exposure (Calderon et al. 2001; Siripitayakunkit et al. 1999).
Since that, a few more articles indicating neurodevelopmental effects of arsenic have been published (Tsai et al. 2003; Wasserman et al. 2006; Wasserman et al. 2004; Watanabe et al. 2003), although the effect estimates are not conclusive, due to limitations in exposure assessments and/or considerations of potential confounding. Considering the fact that millions of families word-wide use drinking water with elevated arsenic concentrations (IARC 2004; Vahter et al. 2006), there is indeed a need for more information on arsenic induced neurotoxicity following early-life exposure. Because of human and experimental studies have demonstrated that arsenic is easily transferred to the fetus (Concha et al. 1998). Thus, effects on child development may result from both pre- and postnatal exposure to arsenic. Therefore, it is highly appreciated that an update and reminder of the tragic poisoning incident is published in a scientific journal, in particular considering the lack of data on effects of early-life exposure to arsenic.
Calderon J, Navarro ME, Jimenez-Capdeville ME, Santos-Diaz MA, Golden A, Rodriguez-Leyva I, et al. 2001. Exposure to arsenic and lead and neuropsychological development in Mexican children. Environ Res 85(2):69-76.
Concha G, Vogler G, Nermell B, Vahter M. 1998. Low-level arsenic excretion in breast milk of native Andean women exposed to high levels of arsenic in the drinking water. Int Arch Occup Environ Health 71(1):42-46.
Dakeishi M, Murata K, Grandjean P. 2006. Long-term consequences of arsenic poisoning during infancy due to contaminated milk powder. Environ Health 5(1):31.
Hamamoto E. 1955. Infant arsenic poisoning by powdered milk. . Nihon Iji Shimpo(No. 1649):3-12 (In Japanese).
IARC. 2004. Volume 84. Some drinking-water disinfectants and Contaminants, including arsenic. Lyon:International Agency for Research on Cancer.
Nakagawa Y, Iibuchi Y. 1970. On the follow-up investigation of Morinaga milk arsenic poisoning. . Igaku no Ayumi 74:1-3.
NRC. 1999. Arsenic in drinking water. Washington, D.C.:National Academy Press.
---. 2001. Arsenic in drinking water: 2001 update. Washington, D.C.:National Academy Press.
Ohira M, Aoyama H. 1972. Epidemiological studies on the Morinaga powdered milk poisoning incident. . PJpn J Hyg 27:500-531.
Siripitayakunkit P, Visudhiphan M, Pradipasen M, Vorapongsathron T. 1999. Association between chronic arsenic exposure and children's intelligence in Thailand.
. In: Arsenic exposure and health effects (Chappell WR, Abernathy CO, R.L. C, eds). New York:Elsevier, 141-150.
Tsai SY, Chou HY, The HW, Chen CM, Chen CJ. 2003. The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence. Neurotoxicology 24(4-5):747-753.
Vahter ME, Li L, Nermell B, Rahman A, El Arifeen S, Rahman M, et al. 2006. Arsenic Exposure in Pregnancy: A Population-based Study in Matlab, Bangladesh Journal of Health, Population and Nutrition 24(2):236-245.
Wasserman GA, Liu X, Parvez F, Ahsan H, Factor-Litvak P, Kline J, et al. 2006. Water Arsenic Exposure and Intellectual Function in Six-Year-Old Children in Araihazar, Bangladesh.
. Environ Health Perspect doi:10.1289/ehp.9501 available via http://dx.doi.org/ [Online 18 October 2006]
Wasserman GA, Liu X, Parvez F, Ahsan H, Factor-Litvak P, van Geen A, et al. 2004. Water arsenic exposure and children's intellectual function in Araihazar, Bangladesh. Environ Health Perspect 112(13):1329-1333.
Watanabe C, Inaoka T, Matsui T, Ishigaki K, Murayama N, Ohtsuka R. 2003. Effects of arsenic on younger generations. J Environ Sci Health A Tox Hazard Subst Environ Eng 38(1):129-139.
WHO. 2001. EHC 224, Arsenic and Arsenic Compounds.
WHO/IPCS. 1981. Environmental Health Criteria 18, Arsenic Geneva:World Health Organization
Yamashita N, Doi M, Nishio M, Hojo H, Tanaka M. 1972. [Recent observations of Kyoto children poisoned by arsenic tainted "Morinaga Dry Milk" (author's transl)]. Nippon Eiseigaku Zasshi 27(4):364-399.
Competing interests
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