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EC number: 615-244-9 | CAS number: 71035-05-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
Toxicity to reproduction: other studies
Description of key information
Weight of Evidence Considerations for Developmental Toxicity Classification of Boric Acid
Although reproductive and developmental effects have been demonstrated in laboratory animals exposed to high doses of boric acid in their feed, similar effects have not been observed in highly exposed human populations or workers. A weight of evidence approach was used in evaluating numerous independent studies on the determination of the hazard of boric acid to humans.
Information that was considered together included results of in vitro tests, animal data, occupational exposure data,epidemiological studies and mechanistic data.
Extensive evaluations of sperm parameters in highly exposed workers in Turkey and China have demonstrated no effects on male fertility. No evidence of developmental effects in humans attributable to boron (B) has been observed in studies of populations with high exposures to boron. Although the epidemiological studies have methodological deficiencies, collectively these studies consistently show an absence of effects in highly exposed populations.
Workers in boron mining and processing industries represent the maximum possible human exposure. However a comparison of blood, semen and target organ boron levels in studies of laboratory animals and human studies shows that boron industry worker exposures are lower than untreated control rats.
Mechanistic data provide possible explanations for the absence of developmental and reproductive effects in humans exposed to high levels of boron.
Recent studies provide evidence that boric acid may act by similar mechanisms in causing developmental effects in mice as sodium salycilate (the natural deacetylated form of aspirin and a rodent teratogen) including effects on Hox gene expression and inhibition of embryonic histone deacetylases. Although aspirin is known to cause developmental effects in laboratory animals, controlled human studies have not demonstrated developmental effects in humans.
Similar mechanisms of action of boric acid and aspirin, and the absence of developmental effects in humans ingesting aspirin suggest that boric acid related developmental effects in humans are unlikely.
Additionally, zinc levels in soft tissue in humans is over 2 times greater than in comparative tissues in rats, which may explain in part the absence of fertility and developmental effects in humans.
There is limited evidence that zinc interacts with boron in the body reducing the toxicity of boron. The interaction of zinc and boric acid is evident by the low acute toxicity of zinc borate (absorbed as boric acid and zinc) with a LD50 value greater than 10,000 mg/kg-body weight in rats compared to disodium tetraborate pentahydrate (similar % boron composition as zinc borate) with a LD50 value of 3300 mg/kg-body weight.
This indicates that zinc interacts with boron in the body reducing the toxicity of boron. Furthermore, no toxic effects were observed in the testes of males (a target organ of boric acid) administered 1000 mg zinc borate/kg/day in a 28-day repeated dose oral gavage toxicity study, equivalent dose of boron of 50 mg B/kg. The LOAEL for testicular effects is 26 mg B/kg body weight.
Based on the total weight of evidence, the data show that it is improbable that boric acid will cause reproductive or developmental effects in human
Introduction
Observations of human populations and workers exposed to high doses of boric acid
have not shown any of the reproductive and developmental effects which
have been demonstrated in laboratory animals
Methods
A weight of evidence approach was used in evaluating numerous independent studies
on the determination of the hazard of boric acid to humans. Separate lines of evidence
included data from occupational exposures, epidemiological studies, reproductive health
assessments, mechanistic studies, in vitro tests, as well as the animal data.
Results and Discussion
Fertility Effects
Extensive evaluations of sperm parameters in highly exposed workers in Turkey and
China have demonstrated no effects on male
fertility (Duydu et a..2011; Robbins et al. 2010, Scialli et al. 2010).
The studies included semen analysis, the most sensitive test for testicular toxicity in humans. . Workers in boron mining and processing industries represent the maximum possible human exposure.
However, tissue concentrations of these workers (Table 1) showed internal B concentrations to be less than measured in rats fed only untreated control
diets (Ball, 2012).
Developmental Effects
No evidence of developmental effects in humans attributable to boron (B) has been observed in studies of populations with high exposures to boron.
Although each study has methodological limitations or deficiencies, collectively these studies consistently show an absence of effects in highly exposed populations
.
Tuccar et al. (1998) investigated reproductive and developmental effects of boron in
three generations of families living in boron rich regions of Turkey.
Daily exposures of 6.77 mg/day for males living in the boron-rich region. 226 families over three
-generations were evaluated in the high-boron area.
•
Cöl et al. (2000) investigated infertility rates, gender ratio, stillbirths and spontaneous abortions, premature births or low birth weights, and infant mortality rates among the families of 799 workers (642 production workers, 157 office workers) at three production facilities in Turkey.
The boron level in drinking water ranged from 1.7 - 9.4 ppm Region I, 2.79 - 5.94 Region II and 0.36 -0.62 Region III.
Chang et al. (2006) evaluated reproductive health in a cohort of boron mining and processing male workers (N=936) and a comparison group of males (N=251) in northeast China. Well water in the boron group ranged from 37 to 600 times the comparison group, and the mean boron concentrations in legumes and potatoes from the boron group was approximately double those found in the comparison group. No statistically significant differences were observed between the boron workers and the comparison group in delay in pregnancy, multiple births, spontaneous miscarriage, induced abortion, stillbirth, tubal or ectopic pregnancy, and boy/girl ratio
.
HDACi and Hox Genes
Recent studies provide evidence that boric acid and sodium salycilate may act by similar
mechanisms in causing developmental effects in mice. Sodium salycilate is the natural deacetylatedform of aspirin and a rodent teratogen. Although aspirin is known to cause
developmental effects in laboratory animals, controlled human studies have not demonstrated
developmental effects in humans. Mechanisms likely include effects on Hoxgene expression
and inhibition of embryonic histone deacetylases
The reported developmental effects in rodents, axial abnormalities, for both boric acid and
sodium salycilate have been attributed to a shift in Hox gene expressions (Wery
et al., 2005, Di Renzo 2008).
Inhibition of histone deacetylases(HDACi) by sodium salicylate and boric acid has been shown as a mechanism of teratogenesis (axial skeletal malformations) in laboratory
animals (Di Renzo et al. 2008).
Recent studies provide evidence that alteration of Hoxgene expression might also be associated with male fertility effects in laboratory animals, a mechanism also linked to developmental effects (
Wery et al. 2005).
Similar mechanisms of action of boric acid and aspirin, and the absence of developmental
effects in humans ingesting aspirin suggest that boric acid related developmental effects in
humans are unlikely.
Zinc
Normal levels of zinc in humans may interact with boron to reduce hazard of toxic effects
.
Zinc levels in soft tissue in humans are over 2 times greater than in comparative tissues
in laboratory animals, see figure below (King et al. 2000; Ranjanet al. 2011; Yamaguchi
et al. 1996).
Zinc has been shown to protect against testicular toxicity of cobalt and
cadmium (Anderson et al. 1993), and developmental toxicity of cadmium (Fernandez et
al. 2003). A similar interaction with boron could explain in part the absence of fertility
and developmental effects in humans
.
The interaction of Zn and boric acid was demonstrated by the low acute toxicity of zinc
borate (ZB) with a LD50 value greater than 10 g/kg-bwin rats (Daniels 1969) compared
to disodium tetraborate pentahydrate with a LD50 value of 3.3 g/kg-
bw (ZB and disodium tetraborate pentahydrate have equivalent boron concentrations.) Furthermore, no toxic effects were observed in the testes of males administered 1000 mg ZB/kg/day in a 28-day repeated dose oral gavage toxicity study, equivalent dose of 50 mg B/kg
bw (Wragget al. 1996). The LOAEL for testicular effects is 26 mg B/kg body weight. This
indicates that Zn interacts with boric acid in the body reducing the toxicity of boric acid
Conclusion
Based on the total weight of evidence, the data show that it is improbable that boric acid
will cause reproductive or developmental effects in humans.
Introduction
Observations
of human populations and workers exposed to high doses of boric acid
have not shown any of the reproductive and developmental effects which have
References
Anderson et al. (1993) Reprod Toxicol 7:49-54.
Ball (2012) Toxicology Letters 211S:188
Chang et al. (2006) AAOHN 54(10) 435 – 443
Cöl et al. (2000) T Klin Med Res 18: 10 - 16.
Daniels (1969) Hill Top Research Inc. Report No T-258.
Di Renzo et al. (2008) Tox Sciences 104(2), 397–404
Duydu et al..(2011) Arch Toxicol 85:589–600
Fernandez et al. (2003) Tox Sciences 76:162-170
King et al. (2000) J. Nutr. 130: 1360S—1366S
Ranjan et al. (2011) Research Report -Fluoride 44(2):83-88
Robbins et al. (2010) Reproductive Toxicology 29: 184 - 190
Scialli et al. 2010) Reproductive Toxicology 29 (2010) 10–24
Tuccar et al. (1998) Biological Trace Element Research 66: 401- 407.
Wery et al. (2005) Reproductive Toxicology 20 (2005) 39–45
Wragg et al (1996) Safe Pharm Laboratories Ltd. Report no.: 801/003.
Yamaguchi et al. (1996) The Journal of Toxicological Sciences, Vol. 21, 17-187, 1996
Mode of Action Analysis / Human Relevance Framework
Weight of Evidence Considerations for Developmental Toxicity Classification of Boric Acid
Although reproductive and developmental effects have been demonstrated in laboratory animals exposed to high doses of boric acid in their feed, similar effects have not been observed in highly exposed human populations or workers. A weight of evidence approach was used in evaluating numerous independent studies on the determination of the hazard of boric acid to humans.
Information that was considered together included results of in vitro tests, animal data, occupational exposure data,epidemiological studies and mechanistic data.
Extensive evaluations of sperm parameters in highly exposed workers in Turkey and China have demonstrated no effects on male fertility. No evidence of developmental effects in humans attributable to boron (B) has been observed in studies of populations with high exposures to boron. Although the epidemiological studies have methodological deficiencies, collectively these studies consistently show an absence of effects in highly exposed populations.
Workers in boron mining and processing industries represent the maximum possible human exposure. However a comparison of blood, semen and target organ boron levels in studies of laboratory animals and human studies shows that boron industry worker exposures are lower than untreated control rats.
Mechanistic data provide possible explanations for the absence of developmental and reproductive effects in humans exposed to high levels of boron.
Recent studies provide evidence that boric acid may act by similar mechanisms in causing developmental effects in mice as sodium salycilate (the natural deacetylated form of aspirin and a rodent teratogen) including effects on Hox gene expression and inhibition of embryonic histone deacetylases. Although aspirin is known to cause developmental effects in laboratory animals, controlled human studies have not demonstrated developmental effects in humans.
Similar mechanisms of actionof boric acid and aspirin, and the absence of developmental effects in humans ingesting aspirin suggest that boric acid related developmental effects in humans are unlikely.
Additionally, zinc levels in soft tissue in humans is over 2 times greater than in comparative tissues in rats, which may explain in part the absence of fertility and developmental effects in humans.
There is limited evidence that zinc interacts with boron in the body reducing the toxicity of boron. The interaction of zinc and boric acid is evident by the low acute toxicity of zinc borate (absorbed as boric acid and zinc) with a LD50 value greater than 10,000 mg/kg-body weight in rats compared to disodium tetraborate pentahydrate (similar % boron composition as zinc borate) with a LD50 value of 3300
mg/kg-body weight.
This indicates that zinc interacts with boron in the body reducing the toxicity of boron. Furthermore, no toxic effects were observed in the testes of males (a target organ of boric acid) administered 1000 mg zinc borate/kg/day in a 28-day repeated dose oral gavage toxicity study, equivalent dose of boron of 50 mg B/kg. The LOAEL for testicular effects is 26 mg B/kg body weight.
Based on the total weight of evidence, the data show that it is improbable that boric acid will cause reproductive or developmental effects in human
Introduction
Observations of human populations and workers exposed to high doses of boric acid
have not shown any of the reproductive and developmental effects which
have been demonstrated in laboratory animals
Methods
A weight of evidence approach was used in evaluating numerous independent studies
on the determination of the hazard of boric acid to humans. Separate lines of evidence
included data from occupational exposures, epidemiological studies, reproductive health
assessments, mechanistic studies, in vitro tests, as well as the animal data.
Results and Discussion
Fertility Effects
Extensive evaluations of sperm parameters in highly exposed workers in Turkey and
China have demonstrated no effects on male
fertility (Duydu et a..2011; Robbins et al. 2010, Scialli et al. 2010).
The studies included semen analysis, the most sensitive test for testicular toxicity in humans. . Workers in boron mining and processing industries represent the maximum possible human exposure.
However, tissue concentrations of these workers (Table 1) showed internal B concentrations to be less than measured in rats fed only untreated control
diets (Ball, 2012).
Developmental Effects
No evidence of developmental effects in humans attributable to boron (B) has been observed in studies of populations with high exposures to boron.
Although each study has methodological limitations or deficiencies, collectively these studies consistently show an absence of effects in highly exposed populations
.
Tuccar et al. (1998) investigated reproductive and developmental effects of boron in
three generations of families living in boron rich regions of Turkey.
Daily exposures of 6.77 mg/day for males living in the boron-rich region. 226 families over three
-generations were evaluated in the high-boron area.
•
Cöl et al. (2000) investigated infertility rates, gender ratio, stillbirths and spontaneous abortions, premature births or low birth weights, and infant mortality rates among the families of 799 workers (642 production workers, 157 office workers) at three production facilities in Turkey.
The boron level in drinking water ranged from 1.7 - 9.4 ppm Region I, 2.79 - 5.94 Region II and 0.36 -0.62 Region III.
Chang et al. (2006) evaluated reproductive health in a cohort of boron mining and processing male workers (N=936) and a comparison group of males (N=251) in northeast China. Well water in the boron group ranged from 37 to 600 times the comparison group, and the mean boron concentrations in legumes and potatoes from the boron group was approximately double those found in the comparison group. No statistically significant differences were observed between the boron workers and the comparison group in delay in pregnancy, multiple births, spontaneous miscarriage, induced abortion, stillbirth, tubal or ectopic pregnancy, and boy/girl ratio
.
HDACi and Hox Genes
Recent studies provide evidence that boric acid and sodium salycilate may act by similar
mechanisms in causing developmental effects in mice. Sodium salycilate is the natural deacetylatedform of aspirin and a rodent teratogen. Although aspirin is known to cause
developmental effects in laboratory animals, controlled human studies have not demonstrated
developmental effects in humans. Mechanisms likely include effects on Hoxgene expression
and inhibition of embryonic histone deacetylases
The reported developmental effects in rodents, axial abnormalities, for both boric acid and
sodium salycilate have been attributed to a shift in Hox gene expressions (Wery
et al., 2005, Di Renzo 2008).
Inhibition of histone deacetylases(HDACi) by sodium salicylate and boric acid has been shown as a mechanism of teratogenesis (axial skeletal malformations) in laboratory
animals (Di Renzo et al. 2008).
Recent studies provide evidence that alteration of Hoxgene expression might also be associated with male fertility effects in laboratory animals, a mechanism also linked to developmental effects (
Wery et al. 2005).
Similar mechanisms of action of boric acid and aspirin, and the absence of developmental
effects in humans ingesting aspirin suggest that boric acid related developmental effects in
humans are unlikely.
Zinc
Normal levels of zinc in humans may interact with boron to reduce hazard of toxic effects
.
Zinc levels in soft tissue in humans are over 2 times greater than in comparative tissues
in laboratory animals, see figure below (King et al. 2000; Ranjanet al. 2011; Yamaguchi
et al. 1996).
Zinc has been shown to protect against testicular toxicity of cobalt and
cadmium (Anderson et al. 1993), and developmental toxicity of cadmium (Fernandez et
al. 2003). A similar interaction with boron could explain in part the absence of fertility
and developmental effects in humans
.
The interaction of Zn and boric acid was demonstrated by the low acute toxicity of zinc
borate (ZB) with a LD50 value greater than 10 g/kg-bwin rats (Daniels 1969) compared
to disodium tetraborate pentahydrate with a LD50 value of 3.3 g/kg-
bw (ZB and disodium tetraborate pentahydrate have equivalent boron concentrations.) Furthermore, no toxic effects were observed in the testes of males administered 1000 mg ZB/kg/day in a 28-day repeated dose oral gavage toxicity study, equivalent dose of 50 mg B/kg
bw (Wragget al. 1996). The LOAEL for testicular effects is 26 mg B/kg body weight. This
indicates that Zn interacts with boric acid in the body reducing the toxicity of boric acid
Conclusion
Based on the total weight of evidence, the data show that it is improbable that boric acid
will cause reproductive or developmental effects in humans.
Introduction
Observations
of human populations and workers exposed to high doses of boric acid
have not shown any of the reproductive and developmental effects which have
References
Anderson et al. (1993) Reprod Toxicol 7:49-54.
Ball (2012) Toxicology Letters 211S:188
Chang et al. (2006) AAOHN 54(10) 435 – 443
Cöl et al. (2000) T Klin Med Res 18: 10 - 16.
Daniels (1969) Hill Top Research Inc. Report No T-258.
Di Renzo et al. (2008) Tox Sciences 104(2), 397–404
Duydu et al..(2011) Arch Toxicol 85:589–600
Fernandez et al. (2003) Tox Sciences 76:162-170
King et al. (2000) J. Nutr. 130: 1360S—1366S
Ranjan et al. (2011) Research Report -Fluoride 44(2):83-88
Robbins et al. (2010) Reproductive Toxicology 29: 184 - 190
Scialli et al. 2010) Reproductive Toxicology 29 (2010) 10–24
Tuccar et al. (1998) Biological Trace Element Research 66: 401- 407.
Wery et al. (2005) Reproductive Toxicology 20 (2005) 39–45
Wragg et al (1996) Safe Pharm Laboratories Ltd. Report no.: 801/003.
Yamaguchi et al. (1996) The Journal of Toxicological Sciences, Vol. 21, 17-187, 1996
Justification for classification or non-classification
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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