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EC number: 236-337-7 | CAS number: 13308-51-5
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- three-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Toxicologic Studies on Borax and Boric Acid
- Author:
- R.J. Weir, Jr. and R.S. Fisher
- Year:
- 1 972
- Bibliographic source:
- Toxicology and Applied Pharmacology 23, 351-364
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test: Three Generation study with two litters per generation.
- Short description of test conditions: Cesarean derived rats were randomized in groups of 8 males and 16 females. The animals received borax or boric acid at 117, 350 and 1170 ppm as boron equivalent in the diet. Prior to initiation of the first breeding phase, the animals were maintained in individual cages and fed their respective diets for 14 weeks. After the 14 week feeding period, 1 male and 2 females were placed in each breeding cage. At 24 hours after birth, the litters were reduced to a maximum of 8 progeny to be raised. The first filial generation (F1a) was carried through weaning and discarded. The parental generation (P1) was rebred to produce their second litter (F1b). At the time of weaning, 16 females and 8 males each from the control and test groups were selected at random and designated the second parental generation (P2) for continuation of the reproduction study. These animals were bred to produce the F2a and F2b litters as before. The F2b litter became the P3 generation and were bred to produce the F3a and F3b litters.
- Parameters analysed / observed: Body weight and food consumption were recorded weekly. With the exception of the P1, P2 and P3 control and test groups, necropsies were performed on all rats. - GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Boric acid
- EC Number:
- 233-139-2
- EC Name:
- Boric acid
- Cas Number:
- 10043-35-3
- Molecular formula:
- BH3O3
- IUPAC Name:
- boric acid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Caesarean-derived rats from Charles River, USA
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: not specified
- Weight at study initiation: 110 - 150 g
- Fasting period before study: no
- Housing: individually except during mating, during mating 1 male and 2 females per cage
- Diet: Purina Laboratory Chow
- Water: not specified
- Acclimation period: not specified
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Rats were exposed from beginning of the study until sacrifice of parents P0, and from weaning till sacrifice for the parents of the F1 and F2-generations.
The high dose group P animals were sterile so only controls, low and mid dose groups were taken to the F2 and F3 generations.
DIET PREPARATION
- Mixing appropriate amounts with Purina Laboratory Chow: The test material was incorporated into the basal diet on a weight/weight basis and thoroughly mixed to provide the desired dietary levels. - Details on mating procedure:
- - M/F ratio per cage: 1:2
- Length of cohabitation: not specified
- Any other deviations from standard protocol: This is a three generation multigeneration study with two matings (two litters) per generation. The F1a, F2a and F3a litters were sacrificed at weaning, and the F1b and F2b litters raised and used for breeding, and the F3b killed at weaning. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Groups of 8 males and 16 females were used for all generations and were exposed from beginning of the study until sacrifice of parents P0, and from weaning until sacrifice of the F1- and F2-generations.
- Frequency of treatment:
- daily
- Details on study schedule:
- - F1 parental animals not mated until [...] weeks after selected from the F1 litters. : not specified
- Selection of parents from F1 generation at the time of weaning.
- Age at mating of the mated animals in the study: not specified
This is a three generation multigeneration study with two matings (two litters) per generation. The F1a, F2a and F3a litters were sacrificed at weaning, and the F1b and F2b litters raised and used for breeding, and the F3b killed at weaning.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 117 ppm (nominal)
- Remarks:
- equivalent to 5.9 mg boron/kg bw/day
- Dose / conc.:
- 350 ppm (nominal)
- Remarks:
- equivalent to 17.5 mg boron/kg bw/day
- Dose / conc.:
- 1 170 ppm (nominal)
- Remarks:
- equivalent to 58.5 mg boron/kg bw/day
- No. of animals per sex per dose:
- 8 males and 16 females per group
- Control animals:
- yes, plain diet
- Positive control:
- no
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: weekly
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption: weekly
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
- Oestrous cyclicity (parental animals):
- no
- Sperm parameters (parental animals):
- viability of sperms was checked
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 8 pups/litter; excess pups were killed and discarded.
PARAMETERS EXAMINED
The following parameters were examined in F1 / F2 / F3 offspring:
number of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain
GROSS EXAMINATION OF DEAD PUPS:
yes, but not described in detail
ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: no
ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY: no - Postmortem examinations (parental animals):
- GROSS NECROPSY
- Gross necropsy was performed on all animals with exception of the P0, P1 and P2 control and test groups
HISTOPATHOLOGY / ORGAN WEIGHTS
not specified - Postmortem examinations (offspring):
- no specified
- Statistics:
- Numerical deviation from the control observations were evaluated by conventional statistical tests using P < 0.05 as the fiducial limit.
- Reproductive indices:
- Fertility index = number of pregnancies / number of matings x 100
- Offspring viability indices:
- Lactation index = number of weaned / number left to nurse x 100
Live birth index = number of pups born alive / number of pups born x 100
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Microscopic examination revealed the lack of viable sperm in the atrophied testes of all males at the 1170 ppm boron equivalent level of boric acid. Evidence was also found of decreased ovulation in the majority of the ovaries examined from the same level females sacrificed following the reproduction study.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Description (incidence and severity):
- lack of viable sperms in the atrophied testes of all males at the high dose group
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- The high dose group of male rats were sterile. An attempt to obtain litters by mating the treated females with the males fed only the basal diet was not successful.
The overall fertility indices for boric acid at levels of 177 and 350 ppm boron were significantly higher than those of the controls (see Tables 1). Higher lactation indices also occurred in rats fed at the same levels of boric acid. Live birth indices were within normal limits in the test groups.
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- fertility
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Remarks:
- boron
- Sex:
- male/female
- Basis for effect level:
- reproductive function (sperm measures)
- reproductive performance
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 58.5 mg/kg bw/day (actual dose received)
- System:
- other: male and female reproductive system
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No gross abnormalities were observed in the organs examined.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Microscopic examination revealed the lack of viable sperm in the atrophied testes of all males at the 1170 ppm boron equivalent level of boric acid. Evidence was also found of decreased ovulation in the majority of the ovaries examined from the same level females sacrificed following the reproduction study.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Description (incidence and severity):
- lack of viable sperms in the atrophied testes of all males at the high dose group
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- The high dose group of male rats were sterile. An attempt to obtain litters by mating the treated females with the males fed only the basal diet was not successful.
The overall fertility indices for boric acid at levels of 177 and 350 ppm boron were significantly higher than those of the controls (see Table 1). Higher lactation indices also occurred in rats fed at the same levels of boric acid. Live birth indices were within normal limits in the test groups.
Effect levels (P1)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Remarks:
- boron
- Sex:
- male/female
- Basis for effect level:
- reproductive function (sperm measures)
- reproductive performance
Target system / organ toxicity (P1)
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 58.5 mg/kg bw/day (actual dose received)
- System:
- other: male and female reproductive system
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- Live birth indices were within normal limits in the test groups (mid and low; high dose group was sterile).
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- weights of progeny was normal compared to those of controls
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No gross abnormalities were observed in the organs examined from weanlings.
- Histopathological findings:
- not specified
- Other effects:
- not examined
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Effect levels (F1)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1a
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Remarks:
- boron
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects described
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1b
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Remarks:
- boron
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects described
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- Live birth indices were within normal limits in the test groups (mid and low; high dose group was sterile).
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- weights of progeny was normal compared to those of controls
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No gross abnormalities were observed in the organs examined from weanlings.
- Histopathological findings:
- not specified
- Other effects:
- not examined
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Effect levels (F2)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F2a
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Remarks:
- boron
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects described
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F2b
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Remarks:
- boron
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects described
Target system / organ toxicity (F2)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- yes
- Lowest effective dose / conc.:
- 58.5 mg/kg bw/day
- Treatment related:
- yes
- Relation to other toxic effects:
- reproductive effects in the absence of other toxic effects
- Dose response relationship:
- yes
- Relevant for humans:
- yes
Any other information on results incl. tables
Table 1: Reproduction data for rats receiving boric acid at 117 and 350 ppm as boron equivalent |
||||||
Index |
Control |
117 ppm |
350 ppm |
Control |
117 ppm |
350 ppm |
|
P0 – F1a |
P0 – F1b |
||||
Fertility index |
62.5 |
87.5 |
81.3 |
60.0 |
87.5 |
75.0 |
Lactation index |
56.3 |
96.2* |
70.3* |
58.8 |
85.6* |
80.0* |
Live birth index |
98.4 |
96.0 |
97.2 |
99.1 |
99.4 |
100.0 |
|
P1 – F2a |
P1 – F2b |
||||
Fertility index |
81.3 |
93.8 |
93.8 |
80.0 |
93.8 |
93.8 |
Lactation index |
48.3 |
79.2* |
83.1* |
92.1 |
81.0 |
98.0 |
Live birth index |
97.8 |
100.0 |
99.4 |
98.6 |
99.4 |
97.9 |
|
P2 – F3a |
P2 – F3b |
||||
Fertility index |
68.8 |
100.0 |
87.5 |
68.8 |
93.8 |
93.8 |
Lactation index |
91.5 |
82.5 |
86.5 |
89.7 |
86.7 |
87.9 |
Live birth index |
100.0 |
99.5 |
97.9 |
100.0 |
99.0 |
98.8 |
* significant higher than control |
Applicant's summary and conclusion
- Conclusions:
- In this three generation study with two litters per generation, were no adverse effects observed on the reproduction of rats receiving a diet containing boric acid at 117 (5.9 mg B/kg bw/day) and 350 (17.5 mg B/kg bw/day) ppm as boron equivalent. Litter size, weights of progeny and appearance were normal compared with those of the controls. The overall fertility indices for the two test compounds at levels of 177 and 350 ppm boron were significantly higher than those of the controls. Higher lactation indices also occurred in rats fed at the same levels of boric acid. Live birth indices were within normal limits in the test groups. No gross abnormalities were observed in the organs examined from either parents or weanlings. The high level test groups fed both borax and boric acid at 1170 ppm as boron equivalent were found to be sterile. An attempt to obtain litters by mating the treated females with the males fed only the basal diet was not successful. Microscopic examination revealed the lack of viable sperm in the atrophied testes of all males at the 1170 ppm (58.5 mg B/kg bw/day) boron equivalent level of boric acid. Evidence was also found of decreased ovulation in the majority of the ovaries examined from the same level females sacrificed following the reproduction study.
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