X hits on this document

PDF document

Local telephone number 907-269-8000 - page 24 / 44

110 views

0 shares

0 downloads

0 comments

24 / 44

Fish Consumption Advice for Alaskans

World Health Organization (WHO) WHO recently established a new Provisional Tolerable Weekly Intake for methylmercury of 1.6 µg/kg body weight/week (or a Provisional Tolerable Daily Intake of 0.22 µg/kg body weight /day) based on the results of the Faroe Islands and Seychelles Islands cohort studies.18 WHO determined a No Observable Effect Level relating to subtle neurobehavioral effects from in utero methylmercury exposure. WHO calculated the No Observable Effect Level of 14 ppm for methylmercury in maternal hair based on the ‘critical endpoint’ of 12 ppm from the Faroe Islands study and 15.3 ppm from the Seychelles Islands study. As noted previously, no effects were attributed to methylmercury exposure in the Seychelles study, and the value of 15.3 ppm represents the mean maternal hair level of mothers in the highest exposure group. Using the standard steady state one-compartment model for methylmercury, and applying an uncertainty factor of 6.4, the No Observable Effect Level represented by a methylmercury concentration of 14 ppm in hair was converted to the Provisional Tolerable Daily Intake of 0.22 µg/kg body weight /day. The Provisional Tolerable Daily Intake corresponds to a hair value of 2.2 ppm and a blood value of 8.7 ppb.18 This Provisional Tolerable Daily Intake applies to children and women of childbearing age.

WHO established a Provisional Tolerable Daily Intake of 0.5µg/kg body weight/day for adults other than women of childbearing age, which the agency reaffirmed in 1999.65 This Provisional Tolerable Daily Intake for the “general population” was established for adults from the Japanese data, and is based on a Lowest Observable Adverse Effect Level for methylmercury in whole blood of 220 ppb (52 ppm hair). WHO used an uncertainty factor of 10 to derive the Provisional Tolerable Daily Intake. Similarly, the Iraqi data provided a Lowest Observable Adverse Effect Level of 240 ppb to 480 ppb in whole blood. For adults the clinical adverse effect detectable at the lowest methylmercury dose is paresthesia (a numbness and tingling sensation) of the mouth, lips, fingers, and toes. The Japanese hair samples were originally analyzed by the dithizone procedure, yielding a value of 52 ppm in the patient with paresthesia with the lowest level of hair mercury. A later reanalysis of the hair from that patient using the newer atomic absorption technique yielded a value of 82.6 ppm.66 All other affected individuals had hair mercury levels above 100 ppm.

Based on available models, a consistent intake of the WHO’s Provisional Tolerable Daily Intake (0.5 µg/kg body weight /day) would correspond to a blood mercury concentration of 20 ppb and a hair mercury concentration of 5 ppm. These exposure levels are one tenth of the Lowest Observable Adverse Effect Level of 220 ppb (blood).

The 1999 WHO Committee also noted “that fish (the major source of methylmercury in the diet) contribute importantly to nutrition, especially in certain regional and ethnic diets, and recommended that, when limits on the methylmercury concentration in fish or on fish consumption are under consideration, the nutritional benefits are weighed against the possibility of harm.”65

U.S. Food and Drug Administration (FDA) FDA followed the approach taken by WHO and derived its action level for commercial sale of 1 ppm mercury (wet weight) in the edible portion of fish based on the Japanese data.67 FDA calculated the action level for edible portions of seafood for interstate commerce by assuming an acceptable methylmercury daily intake of 0.5 µg/kg body weight/day, a half pound (226 g) of fish consumed per week, and a 70 kg adult, resulting in a tolerance level of 1 ppm (1 ppm = [0.5 µg/kg x 7 days x 70 kg]/226 g of seafood consumption).

U.S. Agency for Toxic Substances and Disease Registry (ATSDR) ATSDR derived an oral Minimal Risk Level of 0.3 µg/kg body weight/day68 based on the 66-month evaluation of the Seychelles Child Development Study.52 ATSDR selected the mean maternal hair level of 15.3 ppm in the group with the highest exposure to represent the No Observed Adverse Effect Level and derivation of the chronic oral Minimal Risk Level for methylmercury. An uncertainty factor of 4.5 was used to account for human pharmacokinetic and pharmacodynamic variability (3.0) and a modifying factor of 1.5 to account for the lack of domain-specific tests used in the Seychelles Islands cohort compared to the Faroe Islands cohort.

20

Document info
Document views110
Page views110
Page last viewedSat Dec 10 19:23:29 UTC 2016
Pages44
Paragraphs1112
Words20920

Comments