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TURKEY S COMMENTS vomit Powered By Docstoc
					                                                 ECBI/118/04 Add. 88

                                TURKEY’S COMMENTS

                         on the DRAFT SUMMARY RECORD
                   on the MEETINGS OF THE TC C&L AND PRE-TPC

                               held in Arona, September, 2005.

Although in the summary of the discussions of TC C&L and Pre-TPC meetings on the
classification of boric acid and sodium borates it is emphasized that the available studies on
humans are insufficient to demonstrate the absence of an adverse effect on fertility.
However, there no sufficient data to prove the adverse effects on fertility as well. We believe
that there are quite a number of studies (Annex I) clearly stating long term exposure to
boron does not have any negative results. Most of these studies were conducted in USA and
Turkey where most of the boron reserves exist and the boron production plants are located.

It is also worth to emphasize that there are various ongoing studies throughout the world on
the fertility effects of boron. Two of these studies are conducted in Turkey and the other in
UCLA Center for Occupational & Environmental Health, USA.

Studies being conducted in Turkey are;

   1- Estimation of daily boron intake of humans and determination of its effects on human
      health: The result of this study indicates that the daily boron intake of humans
      exposed to boron in boron mines and factories is around 5,9 0,49 mg/g in boron rich
      regions and 1,21  0,19 mg/g for the control group living outside these boron rich
      areas. This study will also determine that how much of 5,9 mg/l comes from drinking
      water, by inhalation and from food. This study will also correlate the results with the
      statistical work on the fertility in this region. Previous studies made by Prof. Saylı in
      this region lacks the exposure data but current study is also aimed to fill this gap and
      it will be finished by June 2006.
   2- Determination of effects of boron minerals on male fertility and prostate cancer on
      human: In this study, sperm samples have been taken from people who work in
      boron mines and factories and also from control group. The preliminary results
      indicated no reprotoxic effects on humans. This study will be finished by June 2006.

       The study made by University of California Los Angeles is being conducted in the
boron rich regions of China where boron mining and production activities exist. This study is
based on sperm samples and also on DNA fragmentation test.

        Other than these ongoing studies, a regional scale geographical study was conducted
in Northern France (Yazbeck et al., 2005) in which boron blood levels in a group of 180
healthy individuals, correlation with boron content in drinking water were followed by an
assessment of health indicators such as birth rates, mortality rates and sex ratios in zones of
different boron content in drinking water. The results of this study do not support the idea of
deleterious effect of boron on human health, at the boron water level contents found in this
specific region. In fact, there is a tendency toward a beneficial effect (increase in birth rate
and decrease in mortality rate) with low-dose environmental exposure (less than 1 mg/L of
boron) in drinking water.

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        Italian Environment and Primary Prevention Department also intends to carry on
epidemiological studies in order to investigate the possibility of any malformations / adverse
effects on fertility and the relevance of reprotoxicity to humans in Tuscany/Italy where high
exposure levels are present due geysers emissions.

       We believe that it will be rational to withdraw the boric acid and borates from the 30 th
ATP list until receiving more justifiable results from these studies which will give an
opportunity for better determination of effects of these substances on humans. All the
Member States are kindly invited to take part in these studies.

        Please find below our comments on the Summary Record from the Session on
Classification of Boric Acid and Borates of the combined meetings of TC C&L and Pre-TPC
held in Arona in 8 September 2005. We basically give answers to the four questions raised
by ECB Chair as outlined in the Draft Summary Record;

1. Are you satisfied with the information provided by the so far available toxicological data
   based on results of animal tests for classifying borates and boric acid? Do you feel that this
   information gives you a sound scientific basis for classification with regard to the criteria on
   toxicological properties as outlined in Dir. 67/548 ?

      Sodium borates and boric acid are recommended to be classified as toxic to
reproduction Category 2, R60-61 under the Dangerous Substances Directive, based on the
animal data. But all of the reproductive toxicity evidences obtained from animal tests are
related to oral administration at high doses. Although animal testing of boric acid and
sodium borates has yielded reproductive toxic effects at high doses when applied orally,
these dose levels could never be replicated in human beings except by deliberate oral intake
in which case vomiting via an auto reflex action would be induced long before any
reproductive toxic effects were resulted. But this could only happen in an unrealistic
scenario which should not be taken into account while identifying the intrinsic properties of
substances. In all instances of “normal handling and use” (NHU) of these chemicals, the
indicated exposure levels have never been attained or even the levels close to the indicated
ones could not be attainable (Sayli et al., 1998a,b; Sayli, 2001,2003; Sayli et al., 2003).

      The available epidemiological studies (Whorton et al, 1992; 1994 a,b; Sayli et al.,
1998a,b; Sayli, 2003; Col & Col, 2003) indicate that the sodium borates and boric acid do
not have any reproductive toxic effects under normal handling and use criteria stated in
directive 67/548/EEC. Even though these studies should be taken into consideration CWG
do not want to consider these studies with the claim that the available epidemiological
studies are not sufficient.

        Taking all above findings into consideration we believe that the toxicological database
is not sufficient scientifically to come to a conclusion on the classification of sodium borates
and boric acid as outlined in Dangerous Substances Directive.

2. What is your opinion on the weight of evidence of the information included in human
   epidemiological studies provided including the new studies provided and other documents
   submitted by the interested parties after the last discussion in the WG and after the meeting of
   the Specialised Experts until September 2?

       The evaluation of human data is presented in Annex I to this comment letter.

       The human data presented in the Annex I, provide primary suggestive evidence that
long term exposure to boron and its compounds does not seem to effect human
reproductive system. Furthermore, Turkey has the world’s largest natural boron reserves
together with several boron production plants. Approximately thousands of people live in

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these regions covering 52.500 km2 area. Therefore, it is very important to investigate health
effects of boron on people living in these regions of Turkey. The studies of Sayli and his
group, given Annex I, carried out in 2.529 participants and 14.320 marriages over 3
generations, are the largest population studies on the subject. These studies were carried
out in the boron mining, processing and packing facilities as well as residents of high-boron
areas. Indeed some of the people in those areas are not only living there, most of them are
working in the boron mines and processing plants as well, to make living on. In other words,
they live on boron with no negative effects on their entire life. Therefore, the area is a
natural laboratory area and, in spite of some limitations, these studies should have been
considered by the CWG, but apparently they did not.

3. How do you deem the relevance of the animal data for human health hazard assessment?

        In normal handling and use of borates the exposure route for humans is either
inhalation or dermal but not oral. Since the aim of the classification process is to protect the
human health, in order to make a realistic exposure evaluation in the normal handling and
use of chemicals by general public and workers, the real exposure routes should be
considered. This fact is also stated in the directive (Annex VI. However, animal
data from rats come from oral administrations at high doses and these animals have no
vomiting ability at all. Thus the oral route of human exposure is not relevant to the
classification assessment.

         The studies done on laboratory animals identified the fetus and testes as the most
sensitive targets of boron toxicity in several species. However, the fertility as well as the
developmental effects arise from feeding studies in laboratory animals at high
doses. A dose related effect on the testes is observed in rats and mice (Weir and Fischer,
1972; Ku et al., 1993; Fail et al., 1991). Limited and unreliable two-year dietary studies in
dogs is in line with those studies (Weir, 1966a,b; 1967a,b). The testicular effects were
manifested as reversible inhibition of spermiation after 14 days treatment doses around 39
mg B/kg (217 mg boric acid /kg bw/day). Lower dose (26 mg B/kg; 149 mg boric acid/kg
bw/day) causes the same effect in 28 days (Ku et al., 1993). Higher doses caused testicular
atrophy, degeneration of seminiferous tubules, reduced sperm count and a reduction in
fertility (Weir and Fischer, 1972; Lee et al., 1978). Although the mechanism of boron
toxicity is not known, it is suggested that it effects on Setoli cells, resulting in altered
physiological control of sperm maturation and release (Fail et al., 1998). The NOAEL for
this reproductive effects is 17.5 mg B/kg corresponding to 100 mg boric

        Developmental effects have been observed in three rodent species namely rats,
being the most sensitive, mice and rabbits (Price et al., 1996a,b; 1994, 1990; Heindel et al.,
1992). The effects observed in rats include a reduction foetal body weight due to the
inhibition of mitosis and minor skeletal variations (Price et al., 1996a,b; Fail et al., 1998).
The NOAEL for developmental effect is 9.6 mg B/kg which is equal to 54 mg boric

       In general public, humans ingest borates through their diet and drinking water but
these levels do not exceed 4-5 mg B/day corresponding to about 29 mg boric acid/day
(Moore et al., 1995; Moore et al., 1997). The U.S. Food and Nutrition Board (2001)
determined a Tolerable Upper Intake Level (UL) for boron of 20 mg/day.

       Humans do not ingest such high amounts of borates that were used in the animal
studies. Thus, the animal feeding studies do not represent human exposure to borates
under normal handling and use. Moreover, animals used in these experiments are not a
good model for humans. Humans generally would vomit if given orally high doses of boric
acid or borax at levels below the corresponding levels that caused reproductive toxic effects
in rats. The animals used in testing, namely rats, are unable to vomit. Hence, the test

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results from these animals are not acceptable as relevant to humans. Thus, reproductive
toxic effects for borates in animal testing are route specific and dose-specific.

        Annex V to Directive 67/548/EEC (Last update 10 June 2004); Section G. Evaluation
and interpretation, says “When tests are evaluated and interpreted, limitations in the extend
to which the results of animal and in vitro studies can be extrapolated directly to man must
be considered and therefore, evidence of adverse effects in humans, where available, may
be used for confirmation of testing results.” This statement can be interpreted as where
available, human data are considered to be of more relevant in determining the potential
effects of chemical.

4. Do the animal test results and the human epidemiological data give you a comprehensive
   basis for expressing your opinion on the classification of borates and boric acid .

However this question could not be discussed during the meeting. Instead Normal Handling
and Use concept were argued. However our comments on the subject have been given
under Question 1.

                      The legal framework of normal handling and use

 Annex VI to Directive 67/548/EEC present the “ General classification and labelling
requirements for dangerous substances and preparations” The opening clause of this Annex
1.1 states:

    “The object of classification is to identify all the physicochemical, toxicological and
    ecotoxicological properties of substances and preparations which may constitute a risk
    during normal handling and use. Having identified any hazardous properties the
    substances or preparation must then be labelled to indicate the hazard(s) in order to
    protect the user, the general public and the environment.”

  This requirement is further confirmed in 1.4 which states:

    “The label takes account of all potential hazards which are likely to be faced in the
    normal handling and use of dangerous substances and preparations when in the form in
    which they are placed on the market.”

  Moreover in 3.1.4

    “When the classification is to be established form experimental results obtained in
    animal tests the results should have validity for man in that the tests reflect, in an
    appropriate way, the risk to man”

    The term of “ Normal handling and use” is used in several European Directives none of
which explicitly defines it. Nevertheless, based on wordings in these directives and written
commentaries from the European Commission it is stated that normal handling and use
may include a reasonably foreseeable use and may not include neglient and reckless
practices (See references in “Memorandum for the European Commission” by Cleary,
Gottlieb, Steen and Hamilton, p.6. Brussels, September 27, 2001).

    In addition, the technical guidance on chemical risk assessment of European
Commission defines “use” as “normal /intended use or reasonably foreseeable misuse” and
accidental exposure or gross abuse (e.g. suicide attempts) is not addressed in this
document. (European Commission, “Technical Guidance document in support of Commission
regulation (EC) No. 1488/94 on risk assessment for existing substances, Part I, 1996, p.
156). This indicates that “use” refers to normal or foreseeable and not gross abuse in the

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risk assessment process. Dose and the exposure route should be components of
“normal handling and use” concept.

Also in the legal advice on NHU from the Commission as read by the ECB Chair states;

“In order to identify the potentially dangerous intrinsic properties of a substance, one shall
take into account (at least) the following elements:
   The form under which the substance is normally used or may be used
   The normal behaviour of the persons that are handling and using the substance
   Foreseeable and realistic accidents
While identifying the intrinsic properties of a substance, we shall not take into account
unrealistic scenarios:
   We shall not consider as an intrinsic property a property that occurs when the
      substance is deliberately used in an unintended way with an intention to kill/harm:
      whereas the effect on the human body one single absorption of a substance that is not
      intended to be drunk shall be considered (this is a foreseeable accident), the effect of a
      regular daily absorption of the product shall not be taken into account because this
      would correspond to an unrealistic scenario/ a gross abuse.
   The effect of the concentrations that are far above the maximum physically possible
      concentration in human.”

Although these paragraphs are not formalized yet in the Commission, they act as a guidance
for which cases should be considered during classification and labeling decisions. It clearly
describes which criteria should be evaluated as intrinsic properties of a substance and which
shouldn’t be.

    When considered within the scope of above EU definitions of normal handling and use,
as a concept, it may extend to common or reasonably foreseeable misuses, however it
excludes deliberate /unintended uses and gross abuse (unrealistic scenarios) including the
effect of concentrations far above the maximum possible concentrations in human.

      It is quite obvious that the general way of acting of the CWG is to classify the
substances on the basis of the animal data first and if otherwise proven in the future, then to
remove them from the Annex I list. This kind of approach would classify a safe material as

       In the light of afore-mentioned facts, we strongly believe that any classification
decision taken by underestimating the above criteria would cast doubt on its accuracy.
Therefore, sodium borates and boric acid should be removed from 30 th ATP list until the
debate on the Normal Handling and Use issue is clarified, related Technical Guidance
Documents defining the content and concept of normal handling and use is legalized, the Risk
Assessment study is finalized, and the ongoing studies are concluded.

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                                                 ANNEX 1


   There have been some human data regarding occupational and also environmental exposure to boron
and its compounds. Most of these data focuses on the effects on the reproductive system following long-
term exposure and comes from USA and Turkey where most of the World’s boron minerals have been
produced. These studies are listed and evaluated below.

   Tarasenko et al (1972) reported low sperm count, reduced sperm mobility, and elevated fructose
content of seminal fluid in semen analysis of 6 workers who were part of a group of 28 male Russian
workers exposed to high levels of boron salts (22-80 mg/m3) for 10 or more years. Authors indicated that
28 male workers had decreased sexual function compared with 10 control workers. However, the analysis
of data from wives of the men from the exposed and control groups showed no differences. This study has
some limitations such as small sample size, few data on smoking habits, diet, other chemical exposures
and semen analysis method. In response to this study, Whorton et al. (1994a,b, 1992) was conducted a
controlled epidemiology study in US sodium borate workers for reproductive effects.

   Whorton et al (1994 a,b) examined the reproductive effects (reproductive performance, the
standardized birth ratio-SBR) of sodium borates on 542 male employees involved in borax mining and
processing of sodium borates. The route of exposure was primarily by inhalation. Exposure data belongs
to the 10 years period (1980-1990). The authors have demonstrated that SBRs were elevated in each
exposure groups; in high ( as >8 mg/m3 of sodium borate dust ), medium (as 3-8 mg/m3 of sodium borate
dust) and low ( as <3 mg/m3 of sodium borate dust ). Overall data suggest that there are no adverse
paternal effects of occupational exposure from mining and processing of sodium borates. This study was
adequately conducted ,but had some limitations (eg. indirect measures of testicular effects by SBR,
detailed exposure information ).

    Whorton et al (1992) also studied the effects of borates on reproductive function of 68 female
employees. The SBR was 90 (32 offspring observed, 35.4 expected), indicating a deficiency, although not
statistically significant, in live births among female workers exposed to borates. There were no statistical
differences between exposed and controls when the results were analyzed by exposure categories. It is
concluded that exposure to borates did not affect fertility in these population studied. Sample size may
have been small for a meaningful statistical analysis.

   In response to studies above cited, Saylı et al. have initiated in a large scale work on fertility and
infertiliy states of male and female subjects exposed to borates either environmentally, occupationally or
both at several borate regions and processing plants in Turkey . These studies covered all centers of
boron production in Turkey; namely Bigadiç (Balıkesir) , Kestelek (Bursa), Emet-Hisarcik (Kütahya) and
Kirka (Eskişehir) districts.

   Sayli et al. (1998a) assessed boron exposure from drinking water and fertility among residents in two
geographical regions in Turkey. Region  comprised 2368 residents, whereas region  comprised 2319
residents. Boron levels in drinking water were higher in region  (range 2.05-29 mg/l) than in region 
(range 0.30-0.40 mg/l). Ever-married residents from each region who could provide reproductive histories
for three generations of family members represented the study sample; 159 in region  and 154 in region
. The overall percentage of couples with unresolved infertility or those without children across three
generations of the extended families was comparable for the two regions (i.e. 6.0% and 4.6%,
respectively). An excess of female births was found with a male to female ratio of 0.89 in region I which
is similar to Whorton et al. (1994b ) study , ratio of 0.90, whereas in the region II this ratio was 1.04.
Statistical significance was not found. These results suggest that fertility is not adversely affected for this
population. Limitation of this study were small sample size.

   Sayli et al. (1998b) provided further details of the study considered above. Three generation
reproductive histories were taken from 927 subjects in three provinces of Turkey,namely,

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Balıkesir,Kütahya and Eskişehir, with the highest boron deposits. Occupational as well as environmental
exposure would have occurred in all three areas. The boron levels in the drinking water in these areas
were measured to be between 0.70 and 9.05 mg/l. The overall rate of infertility was 3.17% among 916
subjects and 3.0% over three generations. Infertility rates in a boron-free area, Çamlidere, with 625
families studied over three generations was 4.48 %, and in a larger population of 49.856 families
randomly studied by authors throghout the country was 3.84%. An slightly excess of female births was
found with a male to female ratio of 0.98 for live children in some parts of three provinces,this was
significantly different from the boron-free area, Çamlıdere with a ratio of 1.87. However, its significance
needs to be clarified. No matched controls were included but this was not considered to be necessary since
the primary infertility rate of approximately 3% was less than found in most other countries. Lack of
matched controls was not expected to conceal any important adverse affects. The exposure data provided
are limited.

    Tuccar et al (1998) have conducted a study in Bigadiç county (three sub groups; namely, region I
situated on or near boron –rich territories , region II which is far away from borate deposits, region III
which is some close to and some far from deposits and pits) and Kirka town to obtain number of
pregnancies, early infant deaths, congenital malformations, stillbirths and spontaneous abortions. Boron
levels in drinking water were upto 29 ppm in region I,and between 0.30 and 0.50 ppm in region II, no
regularly measurements had been made for region III. In all these three areas, there were active and
former borate workers. There were no differences in the rates of spontaneous abortions or stillbirths in
populations exposed to high or low levels of boron. nfant death rates were higher in region . Congenital
abnormalities occurred in 4/463 conceptions in region  and 1/325 conceptions in Kirka only. The
numbers were too low to permit further statistical analysis.

    Sayli (2001), a continuation of a large scale work going on, has conducted another study to investigate
fertility and infertility states of sibs of participants and of their spouses to prevent overlapping in a
relatively small community with prevailing intermarriages while analyzing pedigree data. The rates of
childless families of this type were 0.0-3.4% among male and 0.9-3.8% among female sibs of subjects,
and 2.3-10.0% among male and 0.0-5.6% among female sibs of his(her) spouse with averages of 2.3% of
1589, 2.6 % of 1589, 4.0% of 1314, and 3.3% of 1436 instances, respectively. Three sets of subgroups,
one from Balya where boron levels in fresh waters were not known (80 participants), one from Çamlıdere
having relatively poor boron soils (75 families) and one from the general population (431 participants)
served as controls. In all of these subgroups, only male and female sibs’ marriages were taken into
account. Statistically differences were not found between cases and controls.
Childless couples in borate families with two or more members involved in borate industry are presented
to address if an aggregation of spouses without offspring occurs. Regarding the borate families with two
or more members, few couples were examples of familial concentration of infertility. There was no
matched control group for comparison. These data support previous studies done by Sayli et al.

   Sayli (2003) has carried out another study to describe the fertility and infertility states of borate (boric
acid, borax decahydrate, borax pentahydrate, sodium perborate tetrahydrate, and sodium perbrate
monohydrate) workers of the Borax and acid plants in order to rule out the possibility of not including
some individuals in his previous studies. Borate exposure of workers was considered in five grades
according to the job classification. Dust concentrations were between 3.33 and 5.95 mg/m3 for workplaces
and between 1.06 and 3.22 mg/m3 for individual samples. The means of duration of exposure were
reported to be 11 and 14 years for first and second phases of this study, respectively. Periodical boron
exposure monitoring data were lacking. Physical examinations or laboratory tests were not attempted,
however medical reports,if available were recorded in this study. At the first phase of this study, 191
workers were interviewed. Among these, there were six infertiles of the primary type with a rate of 3.1%.
Boron-unrelated infertile couples among sibs were found to be 2.6- 3.6 %, and 3.2 % for three-generation
marriages-none being higher than those revealed in different sets of controls. In the second stage of study,
computerized files of all workers (n=712) of the facility and all employees of the general management
sharing the same location were checked without an interview. The primary type of fertility is 3.1 %
among 191 workers first worked out, and 3.4% among workers then analyzed, all coming from the same
environment. The differences not only between these two but also among all other items under discussion

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were found statistically non-significant; that is the rates pertaining to employees (2.7%), to sulfuric acid
plant workers (2.2%), to sibs (3.3%), and to the general population (3.2 to 4.3%) were all alike, without
disturbing the sex ratio. These findings provide that occupational exposure to boron does not seem to have
an adverse effect on human reproduction.

   Sayli et al (2003) have presented overall data from all centers of borate production where boron levels
in drinking water were between 0.2 and 29 ppm in Turkey. Infertility of the primary type among 2529
subjects was 3.1% (range 0.0-6.5%), difference being statistically non-significant. To the pedigree data
the rate was 3.2% covering 14.320 marriages over 3 generations. Marriages of male and female sibs of
subjects and his (her) spouse were ranged from 2.4 to 4.2 %. These figures were not higher than found in
different subgroups of controls and of general population over 50.000 families.

    Culver et al (1994) have demonstrated that the relationship between the workers' boron exposure and
boron intake in animal chronic feeding studies can be looked at by comparing animals at the no-observed-
adverse-effect level (NOAEL) with the high-exposure category workers. In this study high-exposure
category workers with a calculated mean daily boron intake of 27.9 mg boron (0.38 mg boron/kg/day) had
a mean blood-boron level (0.26 µg boron/g blood) that was a factor of 10 lower than the dog and rat at
NOAEL exposure levels, and a mean urine-boron level (10.72 g/mg creatinine) that was a factor of 18
lower than the dog NOAEL exposure levels. Whorton et al (1994) did not find any significant effect on
fertility in the same population above.

    Cöl &Cöl (2003) have determined urinary boron levels of 42 residents living in Hisarcık village in
the Kütahya district of Turkey as previously mentioned in the studies by Saylı (1998b, 2001). Analysis of
Boron concentrations were done to the EPA method 200.8,1994. The mean value of urinary boron was
10.2 g/mg creatinine (range 0.04 - 50.7 g/mg creatinine) (assuming that normally 1 ml of urine contains
1 mg creatinine) this value was 18 times lower than the dog NOAEL exposure levels. Authors’ data were
comparable with that of Culver et al (1994) and Sayli (1998b), Sayli (2001) and Sayli et al (2003) did not
find any significant effect on fertility in the subjects living in the Hisarcik area.

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Çöl M and Çöl C, Environmental boron contamination in waters of Hisarcik area in the Kutahya province
of Turkey. Food Chem.Toxicol.,41:1417-1420 (2003).

Culver B D, Shen PT., Taylor T, Lee-Feldstein A, Anton-Culver H , Strong PL .The relationship of blood-
and urine-Boron to Boron Exposure in Borax-workers and the usefulness of urine-Boron as an exposure
marker. Environ.Health Perspect.102( Suppl.7), 133-137(1994).

Fail PA, J.D. George, J.C. Seely, T.B. Grizzle and J.J. Heindel, Reproductive toxicity of boric
acid in Swiss (CD-1) mice: assessment using the continuous breeding protocol, Fund. Appl.
Toxicol. 17, 225-239 (1991).

Fail PA, Chapin R.E., Price C.J. and Heindel J.J., General, reproductive, developmental and endocrine
toxicity of boronated compounds. Reprod. Toxicol. 12, 1-18, (1998).

Heindel JJ, C.J. Price, E.A. Field, M.C. Marr, C.B. Myers, R.E. Morrissey and Schwetz B A,
Developmental toxicity of boric acid in mice and rats, Fund. Appl. Toxicol. 18, 266-272

Ku, W.W., R. E. Chapin, R. N. Wine, and B. C. Gladen, Testicular toxicity of boric acid
(BA): Relationship of dose to lesion development and recovery in the F344 rat. Reprod.
Toxicol. 7, 305-319 (1993).

Lee I.P., Sherins R.J., Dixon R.L., Evidence for induction of germinal aplasia in male rats by
environmental exposure to boron. Toxicol. Appl. Pharmacol., 45. 577-590 (1978).

Moore, JA and an Expert Scientific Committee. An assessment of boric acid and borax using
the IEHR evaluative process for assessing human developmental and reproductive toxicity of
agents. Repro. Toxicol. 11: 123-160 (1997) and NTIS Technical Report PB96-156005,
March, (1995).

Moore JA, Daston G.P., Fausman EM., Hart W.L., Hughen C., Kimmel C.A., Lamb J.C., Schwetz B.A
and Scialli A.R., An evaluative process for assessing human reproductive and development toxicity of
agents. Reprod. Toxicol. 9, 61-95 (1995).

Price C J, Field E A, Marr M C, Myers C B, Morrissey R E and Schwetz B A . Final report
on the developmental toxicity of boric acid (CAS No 10043-35-3) in Sprague Dawley rats.
NIEHS/NTP (NTP-90-105/NTP-90-105A (and report supplement), Order No. PB91-137570,
 May (1990).

Price CJ, M.C. Marr, C.B. Myers, J.J. Heindel and Schwetz BA, Final report on the developmental
toxicity of boric acid (CAS No 10043-35-3) in New Zealand white rabbits,
NIEHS/NTP Order No. PB92-129550 (1991).

Price CJ, Strong P.L., Marr M.C., Myers C.B. and Murray F.J, Developmental toxicity
NOAEL and postnatal recovery in rats fed boric acid during gestation. Fund. Appl. Toxicol.,
32, 179-193 (1996a).

Price CJ, Marr P.L., Myers C.B. Strong, M.C and Murray F.J., The developmental toxicity of boric acid in
rabbits. Fund. Appl. Toxicol. 34. 176-187 (1996b).

Sayli BS, Tuccar E, Elhan AH, An assessment of fertility in boron-       exposed Turkish subpopulations.
Reprod Toxicol.12(3):297-304 (1998a).

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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. 66(1-3):409-422 (1998b).

Sayli BS, Assessment of fertility and infertility in boron-exposed Turkish subpopulations: 3. Evaluation of
fertility among sibs and in "borate families". Biol Trace Elem Res.81(3):255-267 (2001).

Sayli BS, Low frequency of infertility among workers in a borate processing facility. Biol Trace Elem
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