Review Special Issues

Human biological monitoring of mercury for exposure assessment

  • Mercury (Hg) is a naturally occurring element that has metallic, inorganic and organic forms, each with their own implications for human health. Exposure to mercury primarily occurs by inhalation of metallic mercury vapors and by dietary intake of organic mercury. Early health effects are often not well detected. Therefore, determination of the internal dose is a valuable approach in primary prevention. With this review, we aim to give an overview of the different human biological monitoring (HBM) approaches for short- and long-term exposure to different chemical forms of mercury. We performed a literature search in PubMed using Medical Subject Headings (MeSH) terms as well as free text words. From 417 reviews found, we selected 8 reviews. In addition, online information from national and international health authorities was used. The format of the biological application datasheets from the BIOMONECS project was used to provide an overview of the different biological media for HBM of mercury and methyl mercury. Recent exposure to metallic mercury can be assessed by blood sampling within 24 h after exposure. If children are involved, breath sampling can be considered as a less invasive alternative. Urinary mercury levels mainly reflect long-term inhalation exposure to elemental mercury vapors and divalent mercury. Mercury in blood and hair reflects mid- and long-term exposure to methyl mercury, whereas analysis of a hair segment close to the scalp indicates recent exposure. A flow chart was developed to support the selection of the most suitable HBM approach. For each of the different biological matrices, we provided an overview of advantages and limitations. Depending on the source and duration of exposure, blood, exhaled air, urine or hair can be used for mercury exposure assessment.

    Citation: Romilda Z. Boerleider, Nel Roeleveld, Paul T.J. Scheepers. Human biological monitoring of mercury for exposure assessment[J]. AIMS Environmental Science, 2017, 4(2): 251-276. doi: 10.3934/environsci.2017.2.251

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  • Mercury (Hg) is a naturally occurring element that has metallic, inorganic and organic forms, each with their own implications for human health. Exposure to mercury primarily occurs by inhalation of metallic mercury vapors and by dietary intake of organic mercury. Early health effects are often not well detected. Therefore, determination of the internal dose is a valuable approach in primary prevention. With this review, we aim to give an overview of the different human biological monitoring (HBM) approaches for short- and long-term exposure to different chemical forms of mercury. We performed a literature search in PubMed using Medical Subject Headings (MeSH) terms as well as free text words. From 417 reviews found, we selected 8 reviews. In addition, online information from national and international health authorities was used. The format of the biological application datasheets from the BIOMONECS project was used to provide an overview of the different biological media for HBM of mercury and methyl mercury. Recent exposure to metallic mercury can be assessed by blood sampling within 24 h after exposure. If children are involved, breath sampling can be considered as a less invasive alternative. Urinary mercury levels mainly reflect long-term inhalation exposure to elemental mercury vapors and divalent mercury. Mercury in blood and hair reflects mid- and long-term exposure to methyl mercury, whereas analysis of a hair segment close to the scalp indicates recent exposure. A flow chart was developed to support the selection of the most suitable HBM approach. For each of the different biological matrices, we provided an overview of advantages and limitations. Depending on the source and duration of exposure, blood, exhaled air, urine or hair can be used for mercury exposure assessment.


    Dedicated to Neil Trudinger on his 80th birthday with friendship and admiration.

    H. Hopf established in [3] that an immersion of a topological 2-sphere in R3 with constant mean curvature must be a standard sphere. He also made the conjecture that the conclusion holds for all immersed connected closed hypersurfaces in Rn+1 with constant mean curvature. A. D. Alexandrov proved in [1] that if M is an embedded connected closed hypersurface with constant mean curvature, then M must be a standard sphere. If M is immersed instead of embedded, the conclusion does not hold in general, as shown by W.-Y. Hsiang in [4] for n3 and by Wente in [15] for n=2. A. Ros in [13] gave a different proof for the theorem of Alexandrov making use of the variational properties of the mean curvature.

    In this note, we give exposition to some results in [5,6,7,8,9]. It is suggested that the reader read the introductions of [6,7,9].

    Throughout the paper M is a smooth compact connected embedded hypersurface in Rn+1, k(X)=(k1(X),,kn(X)) denotes the principal curvatures of M at X with respect to the inner normal, and the mean curvature of M is

    H(X):=1n[k1(X)++kn(X)].

    We use G to denote the open bounded set bounded by M.

    Li proved in[5] the following result saying that if the mean curvature H:MR has a Lipschitz extension K:Rn+1R which is monotone in the Xn+1 direction, then M is symmetric about a hyperplane Xn+1=c.

    Theorem 1.1. ([5]) Let M be a smooth compact connected embeded hypersurface without boundary embedded in Rn+1, and let K be a Lipschitz function in Rn+1 satisfying

    K(X,B)K(X,A), XRn, AB. (1.1)

    Suppose that at each point X of M the mean curvature H(X) equals K(X). Then M is symmetric about a hyperplane Xn+1=c.

    In [5], K was assumed to be C1 for the above result, but the proof there only needs K being Lipschitz.

    Li and Nirenberg then considered in [6] and [7] the more general question in which the condition H(X)=K(X) with K satisfying (1.1) is replaced by the weaker, more natural, condition:

    Main Assumption. For any two points (X,A),(X,B)M satisfying AB and that {(X,θA+(1θ)B):0θ1} lies in ¯G, we have

    H(X,B)H(X,A). (1.2)

    They showed in [6] that this assumption alone is not enough to guarentee the symmetry of M about some hyperplane Xn+1=c. The mean curvature H:MR of the counterexample constructed in [6, Figure 4] has a monotone extension K:Rn+1R which is Cα for every 0<α<1, but fails to be Lipschitz. The counterexample actually satisfies (1.2) with an equality. They also constructed a counterexample [6, Section 6] showing that the inequality (1.2) does not imply a pairwise equality.

    A conjecture was made in [7] after the introduction of

    Condition S. M stays on one side of any hyperplane parallel to the Xn+1 axis that is tangent to M.

    Conjecture 1. ([7]) Any smooth compact connected embedded hypersurface M in Rn+1 satisfying the Main Assumption and Condition S must be symmetric about a hyperplace Xn+1=c.

    The conjecture for n=1 was proved in [6]. For n2, they introduced the following condition:

    Condition T. Every line parallel to the Xn+1-axis that is tangent to M has contact of finite order.

    Note that if M is real analytic then Condition T is automatically satisfied.

    They proved in [7, Theorem 1] that M is symmetric about a hyperplane Xn+1=c under the Main Assumption, Condition S and T, and a local convexity condition near points where the tangent planes are parallel to the Xn+1-axis. For convex M, their result is

    Theorem 1.2. ([7]) Let M be a smooth compact convex hypersurface in Rn+1 satisfying the Main Assumption and Condition T. Then M must be symmetric about a hyperplane Xn+1=c.

    The theorem of Alexandrov is more general in that one can replace the mean curvature by a wide class of symmetric functions of the principal curvatures. Similarly, Theorems 1.1 and 1.2 (as well as the more general [7, Theorem 1]) still hold when the mean curvature function is replaced by more general curvature functions.

    Consider a triple (M,Γ,g): Let M be a compact connected C2 hypersurface without boundary embedded in Rn+1, and let g(k1,,kn) be a C3 function, symmetric in (k1,,kn), defined in an open convex neighborhood Γ of {(k1(X),,kn(X)) | XM}, and satisfy

    gki(k)>0,   1in    and    2gkikj(k)ηiηj0, kΓ and ηRn. (1.3)

    For convex M, their result ([7, Theorem 2]) is as follows.

    Theorem 1.3. ([7]) Let the triple (M,Γ,g) satisfy (1.3). In addition, we assume that M is convex and satisfies Condition T and the Main Assumption with inequality (1.2) replaced by

    g(k(X,B))g(k(X,A)). (1.4)

    Then M must be symmetric about a hyperplane Xn+1=c.

    For 1mn, let

    σm(k1,,kn)=1i1<<imnki1kim

    be the m-th elementary symmetric function, and let

    gm:=(σm)1m.

    It is known that g=gm satisfies the above properties in

    Γm:={(k1,,kn)Rn | σj(k1,,kn)>0 for 1jm}.

    It is known that Γ1={kRn | k1++kn>0}, Γn={kRn | k1,,kn>0}, Γm+1Γm, and Γm is the connected component of {kRn | σm(k)>0} containing Γn.

    The method of proof of Theorems 1.2 and 1.3 (as well as the more general [7, Theorems 1 and 2]) begins as in that of the theorem of Alexandrov, using the method of moving planes. Then, as indicated in the introduction of [6], one is led to the need for variations of the classical Hopf Lemma. The Hopf Lemma is a local result. The needed variant of the Hopf Lemma to prove Theorem 1.2 (and Conjecture 1) was raised as an open problem ([7, Open Problem 2]) which remains open. The proof of Theorems 1.2 and 1.3 (as well as the more general [7, Theorems 1 and 2]) was based on the maximum principle, but also used a global argument.

    In a recent paper [9], Li, Yan and Yao proved Conjecture 1 using a method different from that of [6] and [7], exploiting the variational properties of the mean curvature. In fact, they proved the symmetry result under a slightly weaker assumption than Condition S:

    Condition S'. There exists some constant r>0, such that for every ¯X=(¯X,¯Xn+1)M with a horizontal unit outer normal (denote it by ˉν=(ˉν,0)), the vertical cylinder |X(¯X+rˉν)|=r has an empty intersection with G. (G is the bounded open set in Rn+1 bounded by the hypersurface M.)

    Theorem 1.4. ([9]) Let M be a compact connected C2 hypersurface without boundary embedded in Rn+1, which satisfies both the Main Assumption and Condition S'. Then M must be symmetric about a hyperplane Xn+1=c.

    Here are two conjectures, in increasing strength.

    Conjecture 2. For n2 and 2mn, let M be a compact connected C2 hypersurface without boundary embedded in Rn+1 satisfying Condition S (or the slightly weaker Condition S') and {(k1(X),,kn(X)) | XM}Γm. We assume that M satisfies the Main Assumption with inequality (1.2) replaced by

    σm(k(X,B))σm(k(X,A)). (1.5)

    Then M must be symmetric about a hyperplane Xn+1=c.

    The next one is for more general curvature functions.

    Conjecture 3. For n2, let the triple (M,Γ,g) satisfy (1.3). In addition, we assume that M satisfies Condition S (or the slightly weaker Condition S') and the Main Assumption with inequality (1.2) replaced by (1.4). Then M must be symmetric about a hyperplane Xn+1=c.

    The above two conjectures are open even for convex M.

    Conjecture 2 can be approached by two ways. One is by the method of moving planes, and this leads to the study of variations of the Hopf Lemma. Such variations of the Hopf Lemma are of its own interest. A number of open problems and conjectures on such variations of the Hopf Lemma has been discussed in [6,7,8]. For related works, see [11] and [14]. We will give some discussion on this in Section 1.

    Conjecture 2 can also be approached by using the variational properties of the higher order mean curvature (i.e., the σm-curvature). If the answer to Conjecture 2 is affirmative, then the inequality in (1.5) must be an equality. This curvature equality was proved in the following lemma, using the variational properties of the σm-curvature:

    Lemma 1. (Y. Y. Li, X. Yan and Y. Yao) For n2 and 2mn, let M be a compact connected C2 hypersurface without boundary embedded in Rn+1 satisfying Condition S'. We assume that M satisfies the Main Assumption, with inequality (1.2) replaced by (1.5). Then (1.5) must be an equality for every pair of points.

    The proof of Theorem 1.4 and Lemma 1 will be sketched in Section 2.

    We have discussed in the above symmetry properties of hypersurfaces in the Euclidean space. It is also interesting to study symmetry properties of hypersurfaces under ordered curvature assumptions in the hyperbolic space, including the study of the counter part of Theorem 1.1, Theorem 1.4, and Conjecture 2 in the hyperbolic space. Extensions of the Alexandrov-Bernstein theorems in the hyperbolic space were given by Do Carmo and Lawson in [2]; see also Nelli [10] for a survey on Alexandrov-Bernstein-Hopf theorems.

    Let

    Ω={(t,y) | yRn1,|y|<1,0<t<1}, (2.1)
    u,vC(¯Ω),
    uv0,in Ω,
    u(0,y)=v(0,y), |y|<1;u(0,0)=v(0,0)=0,
    ut(0,0)=0,
    ut>0,in Ω.

    We use ku(t,y)=(ku1(t,y),,kn(t,y)) to denote the principal curvatures of the graph of u at (t,y). Similarly, kv=(kv1,,kvn) denotes the principal curvatures of the graph of v.

    Here are two plausible variations of the Hopf Lemma.

    Open Problem 1. For n2 and 1mn, let u and v satisfy the above. Assume

    {whenever u(t,y)=v(s,y),0<s<1,|y|<1, then thereσm(ku)(t,y)σm(kv)(s,y).

    Is it true that either

    uv  near (0,0) (2.2)

    or

    v0  near (0,0)? (2.3)

    A weaker version is

    Open Problem 2. In addition to the assumption in Open Problem 1, we further assume that

    w(t,y):={v(t,y),t0,|y|<1u(t,y),t<0,|y|<1 is C in {(t,y) | |t|<1,|y|<1}.

    Is it true that either (2.2) or (2.3) holds?

    Open Problems 1 and 2 for m=1 are exactly the same as [7, Open Problems 1 and 2], where it was pointed out that an affirmative answer to Open Problem 2 for m=1 would yield a proof of Conjecture 1 by modification of the arguments in [6,7]. This applies to 2mn as well: An affirmative answer to Open Problem 2 for some 2mn would yield a proof of Conjecture 2 (with Condition S) for the m.

    As mentioned earlier, the answer to Open Problem 1 for n = 1 is yes, and was proved in [6]. For n2, a number of conjectures and open problems on plausible variations to the Hopf Lemma were given in [6,7,8]. The study of such variations of the Hopf Lemma can first be made for the Laplace operator instead of the curvature operators. The following was studied in [8].

    Let uv be in C(¯Ω) where Ω is given by (2.1). Assume that

    u>0, v>0, ut>0in Ω

    and

    u(0,y)=0for |y|<1.

    We impose a main condition for the Laplace operator:

    whenever u(t,y)=v(s,y) for 0<ts<1,there Δu(t,y)Δv(s,y).

    Under some conditions we wish to conclude that

    uv  in Ω. (2.4)

    The following two conjectures, in decreasing strength, were given in [8].

    Conjecture 4. Assume, in addition to the above, that

    ut(0,0)=0. (2.5)

    Then (2.4) holds:

    uv  in Ω.

    Conjecture 5. In addition to (2.5) assume that

    u(t,0) and v(t,0) vanish at t=0 of finite order.

    Then

    uv  in Ω.

    Partial results were given in [8] concerning these conjectures. On the other hand, the conjectures remain largely open.

    Theorem 1.4 was proved in [9] by making use of the variational properties of the mean curvature operator. We sketch the proof of Theorem 1.4 below, see [9] for details.

    For any smooth, closed hypersurface M embeded in Rn+1, let V:Rn+1Rn+1 be a smooth vector field. Consider, for |t|<1,

    M(t):={x+tV(x) | xM}, (3.1)

    and

    S(t):=M(t)dσ=area of M(t).

    It is well known that

    ddtS(t)|t=0=MV(x)ν(x)H(x)dσ(x), (3.2)

    where H(x) is the mean curvature of M at x with respect to the inner unit normal ν.

    Define the projection map π:(x,xn+1)x, and set R:=π(M).

    Condition S' assures that ν(ˉx), ˉxM, is horizontal iff ˉxR; R is C1,1 (with C1,1 normal under control); and

    M=M1M2ˆM,

    where M1,M2 are respectively graphs of functions f1,f2:RR, f1,f2C2(R),f1>f2 in R, and ˆM:={(x,xn+1)M | xR}Mπ1(R). Note that f1,f2 are not in C0(R) in general.

    Lemma 2.

    H(x,f1(x))=H(x,f2(x)) xR. (3.3)

    Proof. Take V(x)=en+1=(0,...,0,1), and let M(t) and S(t) be defined as above with this choice of V(x). Clearly, S(t) is independent of t. So we have, using (3.2) and the order assumption on the mean curvature, that

    0=ddtS(t)|t=0=2i=1Mien+1ν(x)H(x)dσ(x)=R[H(x,f1(x))H(x,f2(x))]dx0. (3.4)

    Using again the order assumption on the mean curvature we obtain The curvature equality (3.3).

    For any vC(Rn), let V(x):=v(x)en+1, and let M(t) and S(t) be defined as above with this choice of V(x). We have, using (3.2) and (3.3), that

    0=ddtS(t)|t=0=2i=1Miv(x)en+1ν(x)H(x)dσ(x)=Rv(x)[H(x,f1(x))H(x,f2(x))]dx=0. (3.5)

    Theorem 1.4 is proved by contradition as follows: If M is not symmetric about a hyperplane, then (f1+f2) is not identically zero. We will find a particular V(x)=v(x)en+1, vC2loc(R), to make

    ddtS(t)|t=00,

    which contradicts to (3.5).

    Write

    S(t)=2i=1R1+|[fi(x)+v(x)]t|2dx+ˆS,

    where ˆS, the area of the vertical part of M, is independent of t (since v is zero near R, so the vertical part of M is not moved).

    A calculation gives

    ddtS(t)|t=0=R2i=1[A(f1(x))A(f2(x))]v(x)dx,

    where

    A(q):=1+|q|2,  qRn.

    We know that

    A(q)=q1+|q|2and2A(q)(1+|q|2)3/2I>0  q.

    So [A(q1)A(q2)](q1q2)>0 for any q1q2.

    If (f1+f2)C2loc(R)u{0}, we would take v=(f1+f2) and obtain

    ddtS(t)|t=0=R[A(f1(x))A(f2(x))]v(x)dx=R[A(f1(x))A(f2(x))][f1(x)+f2(x)]dx>0.

    In general, (f1+f2) would not be in C2loc(R). It turns out that Condition S' allows us to do a smooth cutoff near R, and conclude the proof. We skip the crucial details, which can be found in the last few pages of [9].

    Now we give the

    Proof of Lemma 1. The proof is similar to that of Lemma 2, see also the proof of [9, Proposition 3] for more details. We still take V(X)=en+1 and let M(t) be as in (3.1). Consider

    Sm1(t):=M(t)σm1(x)dσ.

    Clearly, Sm1(t) is independent of t.

    The variational properties of higher order curvature [12, Theorem B] gives

    ddtSm1(t)|t=0=mMV(x)ν(x)σm(x)dσ(x),

    thus the same argument as (3.4) yields

    0=ddtSm1(t)|t=0=mMV(x)ν(x)σm(x)dσ(x)=R[σm(x,f1(x))σm(x,f2(x))]dx0.

    We deduce from the above, using the curvature inequality (1.5), that the equality in (1.5) must hold for every pair of points. Lemma 1 is proved.

    Partially supported by NSF grants DMS-1501004, DMS-2000261, and Simons Fellows Award 677077.

    The author declares no conflict of interest.

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