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* Center for Occupational and Environmental
Health, University of California, Los Angeles, California; the
China National Environmental Monitoring
Station, Yuhui Nanlu Chaoyang District, Beijing, China; the
Department of Biostatistics, School of Public
Health; and the School of Nursing, University of
California, Los Angeles, California.
| Correspondence to: Dr Wendie A. Robbins, Room 5-254 Factor Building, Mailcode 956919, UCLA, Los Angeles, CA 90095-6919 (email: wrobbins{at}sonnet.ucla.edu). |
| Received for publication June 20, 2007; accepted for publication September 13, 2007. |
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Abstract |
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Key words: Sperm, spermatogenesis, sex ratio at birth.
10 ppm in the earth's crust; however, some geographic regions
are deficient, and a few have concentrations high enough to be of economic
interest (Woods, 1994;
Howe, 1998). Borates have many
industrial and medical applications, for example, in insulation materials,
fiberglass, fire retardants, textiles, borosilicate glass, adhesives,
detergents/soaps/bleaches, cosmetics, pesticides, soldering and welding
fluxes, and neutron capture cancer therapy. Boron is an essential plant
element and is found in fertilizers
(Richold, 1998). It is likely
an essential human nutrient as well (Park
et al, 2004), and can be found in some vitamin supplements. Demand
for this important element is increasing, and, subsequently, more workers may
be exposed during mining and processing of the ore, and more communities may
be exposed to boron-containing industrial wastes. Evidence for safe versus
adverse workplace or environmental exposures for humans is limited,
particularly for reproductive outcomes. As a result, boric acid was identified
as one of 4 top-priority chemicals in need of field study in humans, according
to a consensus workshop convened to review and prioritize National Toxicology
Program reproductive toxicants (Moorman et
al, 2000). To investigate the effect of a range of boron exposures on reproductive health, we conducted a study in a geographic region in northeast China with extreme variation in environmental boron. This region contains areas rich in borate magnesite ore that support lucrative boron mining and processing plants, as well as geographic areas with very little boron in ground water or soil. Because animal toxicology studies have shown male reproductive system sensitivity at lower doses relative to female or developmental effects (Fail et al, 1991; Ku et al, 1993; Chapin and Ku, 1994; Price et al, 1998), the objective of our study was to evaluate male reproductive outcomes in relationship to total boron exposure that occurred through work, food, and water/liquid consumption. A group of boron workers (n = 936) and a comparison group from an area of low environmental boron (n = 251) were interviewed. An interesting finding based on these interviews (Chang et al, 2006) was that boron workers reported a lower percentage of male offspring at birth (52.45%) compared with men in an area of low environmental boron (54.35%) and China as a nation (58%). A shift in sex ratios at birth toward females for boron workers has been reported previously (Whorton et al, 1994). Thus, a subset of men was evaluated using biologic markers for X and Y chromosomes in ejaculated sperm cells to determine whether there might be an association between boron exposure and sex chromosomes in sperm.
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Materials and Methods |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
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Study Subjects
Study subjects resided in Kuandian City, Liaoning Province, PR China. Men
comprised 3 groups: 63 employed in 5 different boron mines or processing
plants; 39 who did not work in the boron industry but lived in the same area
as the boron mines or processing plants where high levels of environmental
borates were present (these men are referred to as the community
comparison group); and 44 who did not work in the boron industry and
lived in an area of low levels of environmental borates (these men are
referred to as the control group). Participation rates approached 95%
and did not vary significantly across the 3 exposure groups. Retention rates
were 85% across 3 months of follow-up with repeated sampling and did not vary
significantly by exposure group.
Reproductive History and Offspring Health
Interviews were conducted using a 51-item questionnaire guide that included
domains of work, diet, lifestyle, general health, and reproductive and
offspring health as described by Chang et al
(2006). Specific reproductive
data was collected related to numbers and sex of offspring, pregnancy loss,
such as stillbirths, spontaneous, or elected pregnancy terminations, and care
or treatment for reproductive health issues. Selected characteristics of the 3
groups are shown in Table
1.
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Boron Exposure Assessment
Borates dissociate in the body at physiologic pH to boric acid
[B(OH)3] and borate [B(OH) –4] and have
similar effects when dose is calculated as elemental boron
(Culver et al, 1994);
therefore, exposure was calculated in terms of elemental boron
(B10) for this study. A composite of total daily exposure was
generated by collecting 24-hour duplicate food portions and 24-hour duplicate
fluid intakes plus full work shift breathing zone air samples using Institute
of Medicine (IOM) lapel filter cassettes and personal air monitoring pumps
(PCXR series; SKC Inc, Eighty Four, Penn). Boron was measured in blood, urine,
and semen to estimate internal dose. Samples were analyzed by inductively
coupled plasma-mass spectrometry (ICP-MS) for semen, blood, and urine and by
inductively coupled plasma-atomic emission spectrometry (ICP-AES) for dust,
food, and fluid intake samples. A total of 10% field blanks (with a minimum of
2) for each day of sampling were collected and analyzed. Boron analyses were
conducted at the National Research Center of Geo-analysis, Chinese Academy of
Geological Sciences, Beijing, China.
Semen Y:X ratios
Sperm cells were assayed for Y- or X-bearing cells using sperm fluorescence
in situ hybridization (FISH) adapted from Robbins et al
(1995). Briefly, direct
labeled enumerator probes to the alpha satellite region for X (Xp11.1-q11.1)
labeled with fluorophore SpectrumGreen and Y (Yp11.1-q11.1) labeled with
SpectrumOrange were obtained from Vysis Inc (Downers Grove, Ill) as part of
the Aneuvysion DNA Probe Kit. For an internal control on hybridization
efficiency, chromosome 18 (18p11.1-q11.1) labeled with Spectrum Aqua (Vysis
Inc) was used. In situ hybridization was performed on 7 µL semen dried onto
microscope slides and decondensed with 10 mM dithiothreitol (DTT; Sigma, St
Louis, MO) in 0.1 M Tris buffer, pH 7.6, on ice for 20 minutes, followed by 4
mM lithium diiodosalicylate (LIS; Sigma) in 0.1 M Tris buffer, pH 7.6, at room
temperature for 28 minutes. Slides were air dried and then denatured at 75
°C for 3 minutes in 70% formamide, 2x SSC (0.15 M sodium chloride,
0.015 M sodium citrate), pH 7.0, followed by ethanol incubations of 70%, 85%,
and 100% for 2.5 minutes each. Predenatured probe (10 µL) was added to each
slide, then covered by a 22 x 22 mm cover slip and hybridized overnight
at 37 °C. Slides then were washed in 50% formamide, 2x SSC at 45
°C, for 10 minutes followed by a 10-minute wash in 2x SSC at 45
°C, a 10-minute wash in 1x SSC at 45 °C, and a 10-minute wash in
1xSSC at room temperature. Air-dried slides were counterstained with a 9
µL mixture of DAPI 125 ng/mL in mounting media (Vysis), covered by a 22
x 22 mm cover slip, and stored at 4 °C until scoring. Sperm nuclei
were observed via fluorescence microscopy using a Zeiss Axiophot microscope
with DAPI/FITC/Texas Red triple band pass filter set-up (61002; Carl Zeiss,
Inc, Thornwood, NY) for simultaneous visualization of DAPI and the Spectrum
orange, green, and aqua fluorochromes (Chroma Technology Corp, Brattleboro,
Vt). A single band pass emission filter for green (41001: exciter 480/40,
emitter 535/50), red (41004: exciter 560/55, emitter 645/75), or aqua
(30-150092: exciter 420/30, emitter 460/40) was used to confirm discrimination
of green, orange, or aqua signals during scoring. Slides were analyzed using
strict scoring criteria to discriminate normal from abnormal fluorescence
phenotypes as described by Ong et al
(2002). Sperm were scored only
if they were morphologically preserved with no clumping or overlapping and if
they had a well-defined outline and tail. A total of 5000 cells were scored
per sample, and a single scorer analyzed all samples. Hybridization efficiency
was greater than 99%. Slides were coded so the scorer did not know whether the
subject was from the boron worker group or a comparison group. Prior to
beginning the scoring, the study group slides were mixed so that slides were
scored in random order.
Statistical Analyses
All variables were plotted, and those that were highly skewed (eg, the
biologic boron measures) were log transformed to normalize the data prior to
analysis. 
2 tests and 1-way ANOVA were used to evaluate
relationships between the reproductive outcome variables (eg, elective
abortion, spontaneous abortion, gender of offspring), demographic, lifestyle,
and environmental variables (eg, age, education, smoking, diet). To examine
differences with respect to the sex of offspring at birth, we compared the
proportion of subjects with more male than female offspring at birth across
the groups (thus, men with equal numbers of male and female offspring at birth
were not included in this comparison). Those variables that were significantly
different among the 3 groups were compared between pairs of groups with the
t test with Tukey multiple comparison correction. To investigate
possible correlates of the Y:X ratio, univariate linear regression models were
constructed with the Y:X ratio as the outcome and the following variables as
predictors: conventional semen parameters (total concentration, total motile
cells, morphology), days of abstinence prior to semen collection, boron in
biologic fluids, total daily boron exposure, diet, years of marriage,
medications, chronic medical conditions, exposures to other known reproductive
toxicants, or history of reproductive problems. A multiple linear regression
model for Y:X ratio was constructed to determine whether the effect of group
remained significant after controlling for potential confounders that might
affect semen quality. The final model included terms for age, smoking,
alcohol, education, and pesticide exposure. All statistical analyses were
carried out in SAS (version 9.1.3; SAS Institute Inc, Cary, NC) and R
(www.r-project.org).
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Results |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
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Boron in biologic fluids of the 146 men varied across the 3 groups (ANOVA P < .0001), with boron workers being higher on all measures (blood, semen, urine) than men sampled from either the community with high environmental boron (t test P < .0001) or controls from the low–environmental boron area (t test P < .0001). Nonboron workers from the community with high environmental boron also had more boron in their biologic fluids than men in the low–environmental boron area (t tests: blood, P < .03; semen, P = .06; urine, P = .02). Total boron exposure was estimated for a convenience sample of men who collected 24-hour food/fluid intakes and workplace inhalable dust monitoring. Boron workers had the highest total exposure and differed from both comparison groups (t test P < .0001). Total exposure for nonboron workers living in the community with high environmental boron was nearly twice that of men in the control group, but this difference did not reach statistical significance (t test P < .06). Biologic measures of internal dose were correlated with total boron exposure (Pearson correlation for total exposure and boron in blood = 0.63, P < .0001; semen = 0.80, P < .001; and urine = 0.79, P < .0001). These relationships are shown in Table 2.
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The 3 groups differed in ratio of Y-to X-bearing sperm in their ejaculates, as shown in Table 2 (ANOVA P < .0001). Among the 146 men, boron workers had a lower ratio of Y-bearing to X-bearing sperm compared with men in both the high–environmental boron area (t test P < .0001) and low–environmental boron area (t test P < .0001). Of note, the community comparison group living in an area with high environmental boron also had significantly lower sperm Y:X ratios than the low–environmental boron control group (t test P < .0001). Linear regression analysis adjusting for age, smoking, alcohol, education, and pesticide exposure found a significant relationship between Y:X ratio and the boron worker group (P < .0001) and community comparison group (P = .0001) when using the control group from the area of low environmental boron as baseline, as shown in Table 3. Linear regression models of logged boron in biologic fluids on Y:X ratio were all statistically significant (blood P = .02, semen P = .0003, urine P = .005). A separate within-group regression between Y:X ratio and the biologic boron measures found no statistically significant within group correlations.
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Discussion |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
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1.3 births per man, and it would have required a sample size of 1700
total births to boron-exposed men and an equal number of total births to
boron-unexposed men to verify statistically significant differences between
the groups if total numbers of male offspring were used. The finding of
reduced Y:X ratios in the present study replicated our pilot data collected
the year prior on 60 boron workers and 9 controls (P < .009, data
not shown). The Y:X sperm ratios reported for men from the area of low
environmental boron in our study are consistent with those reported for other
cohorts of healthy men from around the world (Figure, constructed from data of
published studies by Shi and Martin,
2000; Ong et al,
2002; and Rubes et al,
2002, where enough detail is available on Y- and X-bearing sperm
in the publication to construct box and whisker
plots).
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The lower Y:X ratios in sperm of boron-exposed men could not be explained by other variables tested, including conventional semen parameters (total concentration, total motile cells, morphology), additional elements assayed simultaneously in the biologic fluids (Ca, Mg, Pb, Se, Cr, Cu, Sr, Zn), or particulars of diet, years of marriage, medications, chronic medical conditions, exposures to other known reproductive toxicants, history of reproductive problems, elective and spontaneous abortion, or days of abstinence prior to the semen collection. Within each comparison group, correlations between biologic levels of boron and Y:X ratio were not significant; however, previous modeling of creatinine corrected urine boron as a predictor of total exposure (Xiaoru et al, 2006) demonstrated a boron exposure–dose relationship that predicted best for high exposures and not as well for low exposures. This plus the small within-group numbers may explain a lack of within-group statistical significance.
Only a few published epidemiologic studies have examined human male
reproductive health related to environmental or workplace borates, and these
studies have reported either no adverse effect
(Whorton et al, 1994; Sayli,
1998,
2003; Yazbeck et al, 2005) or
testicular atrophy and sterility
(Tarasenko et al, 1972). It is
interesting that epidemiologic investigations that collected data on offspring
of men with high exposures to borates all suggest trends in the sex ratio at
birth toward females when the ratio is compared across exposure groups
(Whorton et al, 1994;
Chang et al, 2006) or compared
to year-appropriate ratios for the home country of the study (Sayli,
1998,
2003) or the sex ratio
1.05–1.06 generally reported for most countries of the world
(Mathews and Hamilton, 2005;
Yazbeck et al, 2005). For example, the drinking water study by Yazbeck et al
(2005) reported slightly higher female offspring in regions of France with
boron in water of 
0.3 mg/L compared with geographic regions with boron in
water ranging from 0.00–0.09 mg/L based on 72 993 births and 84 305
births, respectively. This difference (sex ratio 1.05 versus 1.04) was not
statistically significant. Of note, Yazbeck et al measured blood boron in a
subset of their population using military recruits from various regions,
including 36 from the region with comparatively high boron in water. The
average blood boron level for these recruits was 27% lower than the average
blood boron for the 68 workers in our boron industry study. None of the above
publications reported on Y:X ratios in sperm. In our study, we were able to
demonstrate a shift in Y:X ratio across the groups (P < .0001)
that was consistent with self-report of a shift toward female offspring
(P < .03). To date, published animal toxicology studies have not
reported on boron-related changes in offspring sex ratios.
Shifts in sex ratios at birth toward more females have been reported for extreme exposures to men—for example, the 1979 Yucheng polychlorinated biphenyl (PCB)–contaminated cooking oil poisonings (del Rio Gomez et al, 2002), the 1976 Seveso tetrachlorodibenzo-p-dioxin (TCDD) explosion disaster (Mocarelli et al, 2000)—as well as workplace exposures, such as dibromochloropropane (DBCP) exposures (Whorton and Foliart, 1983). In each of these cases, significant changes in conventional semen quality were noted. Markers of Y- and X-bearing sperm were not analyzed, so effects after fertilization cannot be ruled out. Tiido et al (2005) reported a significant association between Y:X ratios in sperm and the persistent organochlorine pollutants CB-153 (P = .05) and p,p'-DDE (P < .001) in 149 Swedish fishermen. The magnitude of change in Y:X ratio in the Tiido study (1.6% and 0.8%, respectively) did not change observed sex ratios in offspring of the fishermen and are considerably smaller than the 6% change in Y:X ratio found and replicated by us between boron workers and controls.
Delayed release of sperm into the lumen of the seminiferous tubule (retained sperm) and retention of residual cytoplasm in maturing sperm cells (residual bodies) are the first signs of boron toxicity noted in nonhuman test systems (Wang et al, 2005; Namekawa et al, 2006), although Y:X ratios at this juncture have not been studied. Data from our study are epidemiologic (observational); however, they fit with mechanistic models of disruption of normal events during the process of meiotic sex chromosome pairing and inactivation, subsequent segregation of sex chromosomes, as well as postmeiotic gene reactivation patterns conferring selective advantage to X-bearing sperm during spermiation. If fewer Y-bearing sperm remain following errors in meiotic gene inactivation/postmeiotic reactivation patterns that confer selective advantage to X-bearing sperm and loss of Y chromosome sperm, overall lower sperm concentrations in the ejaculate might be expected. For our data, based on the change in the Y:X ratio found, we would expect a 3% decrease in total concentration. A decrease was observed, although it did not reach statistical significance. Given the level of variability in sperm concentration among the study subjects, the statistical power to detect this expected decrease in concentration was only 6%, indicating that even if there was a change, it would be too small to detect for sperm concentration with the current sample size. Evidence in the ejaculated sperm cells of residual bodies or morphologic size/shape differences were not seen, nor were differential levels of apoptotic sperm carrying X versus Y chromosomes (data not shown), suggesting the shift in Y:X ratio occurred earlier in spermatogenesis, at some point before or close to spermiation.
Lower Y:X ratio in sperm cells of boron workers indicates paternal origin for the shift seen in sex ratios at birth rather than an effect of maternal factors or selective survival of the female fetus. Families in northeast China face strong socio-political and cultural preference for sons. Although we cannot know the sex of pregnancies that were not brought to term in our study group, we did see that boron workers were not different from men in the comparison groups in numbers of reported elective pregnancy terminations, spontaneous pregnancy losses, or stillbirths.
Sex ratio at birth has an impact on critical population dynamics (eg, doubling time), socio-economics, and health factors. The ratio of males to females at birth has been used to assess the effects of environmental and other factors on human reproductive health (Mathews and Hamilton, 2005) but reflects maternal, fetal, and paternal components. Our findings demonstrate both changes in sex ratios at birth and changes in Y-to X-bearing sperm. We present these findings as evidence that exogenous environmental or workplace exposures can result in selective genetic pressure in human males (X- versus Y-bearing sperm) and that this could be expressed as changed sex ratios in offspring. A decline in the number of males born relative to females has been reported in a number of countries over the past few decades (Davis et al, 1998; Mathews and Hamilton, 2005). Social and environmental scientists implicate a range of population stressors for this downward trend, including, most commonly, environmental pollution, increasing parental ages, parental hormones, and race (Mathews and Hamilton, 2005; Bay et al, 2006; Catalano and Bruckner, 2006; James, 2006). Findings confirm the need to be concerned about changing sex ratios at birth for humans that are experienced in some areas around the world, as well as the need to explore the underlying etiology.
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Acknowledgments |
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Footnotes |
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References |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Catalano R, Bruckner T. Secondary sex ratios and male lifespan:
damaged or culled cohorts. Proc Natl Acad Sci U S A. 2006; 103: 1639
–1643.
Chang BL, Robbins WA, Wei F, Xun L, Wu G, Li N, Elashoff DA. Boron workers in China: Exploring work and lifestyle factors relevant to boron exposure. AAOHN J. 2006; 54: 435 –443.[Medline]
Chapin RE, Ku WW. The reproductive toxicity of boric acid. Environ Health Perspect. 1994; 102(suppl 7): 87 –91.
Culver BD, Shen PT, Taylor TH, Lee-Feldstein A, Anton-Culver H, Strong PL. The relationship of blood- and urine-boron to boron exposure in borax-workers and usefulness of urine-boron as an exposure marker. Environ Health Perspect. 1994; 102(suppl 7): 133 –137.
Davis DL, Gottlieb MB, Stampnitzky JR. Reduced ratio of male to
female births in several industrial countries: a sentinel health indicator?
JAMA. 1998;279: 1018
–1023.
del Rio Gomez I, Marshall T, Tsai P, Shao YS, Guo YL. Number of boys born to men exposed to polychlorinated byphenyls. Lancet. 2002;360: 143 –144.[CrossRef][Medline]
Fail PA, George JD, Seely JC, Grizzle TB, Heindel JJ. Reproductive toxicity of boric acid in Swiss (CD-1) mice: assessment using the continuous breeding protocol. Fundam Appl Toxicol. 1991; 17: 225 –239.[CrossRef][Medline]
Howe PD. A review of boron effects in the environment. Biol Trace Elem Res. 1998; 66: 153 –166.[Medline]
James WH. Possible constraints on adaptive variation in sex ratio at birth in humans and other primates. J Theor Biol. 2006; 238: 383 –394.[Medline]
Ku WW, Chapin RE, Wine RN, Gladen BC. Testicular toxicity of boric acid (BA): relationship of dose to lesion development and recovery in the F344 rat. Reprod Toxicol. 1993; 7: 305 –319.[CrossRef][Medline]
Mathews TJ, Hamilton BE. Trend analysis of the sex ratio at birth in the United States. Natl Vital Stat Rep. 2005; 53: 1 –17.[Medline]
Mocarelli P, Gerthoux PM, Ferrari E, Patterson DG Jr, Kieszak SM, Brambilla P, Vincoli N, Signorini S, Tramacere P, Carreri V, Sampson EJ, Turner WE, Needham LL. Paternal concentrations of dioxin and sex ratio of offspring. Lancet. 2000; 355: 1858 –1863.[CrossRef][Medline]
Moorman WJ, Ahlers HW, Chapin RE, Daston GP, Foster PM, Kavlock RJ, Morawetz JS, Schnorr TM, Schrader SM. Prioritization of NTP reproductive toxicants for field studies. Reprod Toxicol. 2000; 14: 293 –301.[CrossRef][Medline]
Namekawa SH, Park PJ, Zhang LF, Shima JE, McCarrey JR, Griswold MD, Lee JT. Postmeiotic sex chromatin in the male germline of mice. Curr Biol. 2006; 16: 660 –667.[CrossRef][Medline]
Ong TD, Xun L, Perreault SD, Robbins WA. Aneuploidy and chromosome breakage in swim-up versus unprocessed semen from twenty healthy men. J Androl. 2002;23: 270 –277.[Abstract]
Park M, Li Q, Shcheynikov N, Zeng W, Muallem S. NaBC1 is a ubiquitous electrogenic Na+-coupled borate transporter essential for cellular boron homeostasis and cell growth and proliferation. Mol Cell. 2004;16: 331 –341.[CrossRef][Medline]
Price CJ, Strong PL, Murray J, Goldberg MM. Developmental effects of boric acid in rats related to maternal blood boron concentrations. Biol Trace Elem Res. 1998; 66: 359 –372.[Medline]
Richold M. Boron exposure from consumer products. Biol Trace Elem Res. 1998;66: 121 –129.[Medline]
Robbins WA, Baulch JE, Moore IID, Weier H-U, Blakey D, Wyrobek AJ. Three-probe fluorescence in situ hybridization to assess chromosome X, Y, 8 aneuploidy in sperm of 14 men from two healthy groups: evidence for an age effect. Reprod Fertil Dev. 1995; 7: 799 –809.[CrossRef][Medline]
Rubes J, Vozdova M, Robbins WA, Rezacova O, Perreault SD, Wyrobek AJ. Stable variants of sperm aneuploidy among healthy men show associations between germinal and somatic aneuploidy. Am J Hum Genet. 2002;70: 1507 –1519.[CrossRef][Medline]
Sayli BS. An assessment of fertility in boron-exposed Turkish subpopulations: 2. Evidence that boron has no effect on human reproduction. Biol Trace Elem Res. 1998; 66: 409 –422.[Medline]
Sayli BS. Low frequency of infertility among workers in a borate processing facility. Biol Trace Elem Res. 2003; 93: 19 –30.[CrossRef][Medline]
Shi Q, Martin RH. Spontaneous frequencies of aneuploid and diploid sperm in 10 normal Chinese men: assessed by multicolor fluorescence in situ hybridization. Cytogenet Cell Genet. 2000; 90: 79 –83.[CrossRef][Medline]
Tarasenko NIU, Kasparov AA, Strongina OM. [Effect of boric acid on the sexual function in males.] Gig Tr Prof Zabol. 1972; 16: 13 –16.[Medline]
Tiido T, Rignell-Hydbom A, Jonsson B, Giwercman YL, Rylander L,
Hagmar L, Giwercman A. Exposure to persistent organochlorine pollutants
associates with human sperm Y:X chromosome ratio. Hum
Reprod. 2005;20: 1903
–1909.
Wang PJ, Page DC, McCarrey JR. Differential expression of
sex-linked and autosomal germ-cell-specific genes during spermatogenesis in
the mouse. Hum Mol Genet. 2005; 14: 2911
–2918.
Whorton D, Haas JL, Trent L, Wong O. Reproductive effects of sodium
borates on male employees: birth rate assessment. Occup Environ
Med. 1994;51: 761
–767.
Whorton MD, Foliart DE. Mutagenicity, carcinogenicity and reproductive effects of dibromochloropropane (DBCP). Mutat Res. 1983;123: 13 –30.[Medline]
Woods WG. An introduction to boron: history, sources, uses, and chemistry. Environ Health Perspect. 1994; 102(suppl 7): 5 –11.
Xing XR, Wei FS, Hu W, Wu GP, Wang CL. Prediction of human daily boron exposure by urine boron concentration. Environ Sci. 2006;27: 1208 –1211.
Yasbeck C, Kloppmann W, Cottier R, Sahuquillo J, Debotte G, Huel G. Health impact evaluation of boron in drinking water: a geographical risk assessment in Northern France. Environ Geochem Health. 2005; 27: 419 –427.[CrossRef][Medline]
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