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EC number: 435-580-8 | CAS number: 56553-60-7
- 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 fertility
Link to relevant study records
- Endpoint:
- three-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication with the decomposition product boric acid which meets basic scientific principles
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: No guideline specified, but equivalent to the standard 3 generation study/multi-generation studies normally used at that time.
- Principles of method if other than guideline:
- No guideline specified, but equivalent to the standard 3 generation study/multi-generation studies normally used at that time.
- GLP compliance:
- no
- Remarks:
- prior to GLP
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Cesarean-derived from Charles River
- Weight at study initiation: 110 - 150 g
- Housing: Individidually housed
- Diet (e.g. ad libitum): Purina Laboratory Chow; ad libitum - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on mating procedure:
- - M/F ratio per cage: 1:2
- Length of cohabitation: 21
- Breeding schedule:
24 h after birth, the F1 litters were reduced to a maximum of eight pups and discarded when they reached 21 days of age.
The parents in the control and two lower test groups were mated again. At the time of resulting weaning animals (F1B) 16 females and 8 males from the control and two test groups were chosen randomly and designated as the second parental generation (P2) for continuation of the reproduction study. These animals were bread to produce the F2A and F2B litters as before with the F2B litter becoming the P3 generation which was bread to produce the F3A and F3B litters.
Additional breeding of the high dose P1 with control males was performed to investigate whether the female reproductive system was affected. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- From premating for 14 days until scheduled necropsy of F3 generation
- Frequency of treatment:
- Daliy, ad libitum
- Details on study schedule:
- - Schedule:
F1a, F2a and F3a litters were sacrificed at weaning, while F1b and F2b litters raised and used for breeding.
- Remarks:
- Doses / Concentrations:
34, 100, 336 mg/kg bw/d
Basis:
nominal in diet
Boric acid - Remarks:
- Doses / Concentrations:
670, 2000, 6700 ppm
Basis:
nominal in diet
Boric acid - Remarks:
- Doses / Concentrations:
5.9, 17.5, 58.8 mg/kg bw/d
Basis:
nominal in diet
Element Boron - No. of animals per sex per dose:
- P1: 8 males and 16 females
P2: 8 males and 16 females
P3: 8 males and 16 females - Control animals:
- yes, plain diet
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: weekly
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): weekly - Sperm parameters (parental animals):
- Parameters examined in all male parental generations: analysis of sperm viability
- Litter observations:
- STANDARDISATION OF LITTERS
- Yes, maximum of 8 pups/litter; excess pups were killed and discarded.
PARAMETERS EXAMINED
The following parameters were examined in all offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities - Reproductive indices:
- Fertility index = number of pregnancies/number of matings x 100
Lactation index = number weaned/numbe left to nurse x 100 - Offspring viability indices:
- Live birth index= number of pups born alive/number of pups born x 100
- Clinical signs:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Reproductive performance:
- effects observed, treatment-related
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Remarks:
- Boric acid in diet
- Sex:
- male/female
- Basis for effect level:
- other: Arophied testes in all P1 males
- Dose descriptor:
- NOAEL
- Effect level:
- 17.5 mg/kg bw/day (nominal)
- Based on:
- element
- Remarks:
- Boron in diet
- Sex:
- male/female
- Basis for effect level:
- other: atrophied testes in all P1 males
- Dose descriptor:
- LOAEL
- Effect level:
- 336 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Remarks:
- Boric acid in diet
- Sex:
- male/female
- Basis for effect level:
- other: histopathology;
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Remarks:
- Boric acid in diet
- Sex:
- male/female
- Basis for effect level:
- other: Atrophied testes in all P1 males
- Remarks on result:
- other: Generation: F1, F2 (migrated information)
- Dose descriptor:
- NOAEL
- Effect level:
- 17.5 mg/kg bw/day (nominal)
- Based on:
- element
- Remarks:
- Boron in diet
- Sex:
- male/female
- Basis for effect level:
- other: Atrophied testes in all P1 males
- Remarks on result:
- other: Generation: F1, F2 (migrated information)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- not examined
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Equivalent to 350 ppm of Boron in the diet.
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- other: None
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Equivalent to 350 ppm of Boron in the diet.
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects in mid and low dose groups in any generation.
- Reproductive effects observed:
- not specified
- Conclusions:
- Based on the sterility in the highest dose group, the NOAEL for reproduction was found to be 100 mg/kg bw/d Boric acid in diet corresponding to 17.5 mg/kg bw Boron.
- Executive summary:
In a three generation study in rats groups of 8 males and 16 females were treated with boric acid equivalent to 0, 5.9, 17.5 and 58.8 mg boron/kg bw/day. The high dose P1-generation failed to produce litter. Also when females of that group were mated with untreated males they had no offspring, indicating that the female reproduction was affected. A decreased ovulation in the majority of ovaries examined in that group was mentioned not to be sufficient to explain the observed infertility since only ovaries of high dosed females were examined. However, gross necropsy revealed atrophied testes in all P1 males at 58.8 mg boron/kg bw/day. Based on the sterility in the highest dose group, the NOAEL for reproduction was found to be 100 mg/kg bw/d Boric acid in diet corresponding to 17.5 mg/kg bw Boron.
Reference
The high dose group (58.5 mgB/kg bw) males and females showed clinical signs of toxicity with rough fur, scaly tails, respiratory distress and inflamed eyelids.
REPRODUCTIVE FUNCTION:
When females of that group were mated with untreated males they had no offspring, indicating that the female reproduction was affected. A decreased ovulation in the majority of ovaries examined in that group was mentioned not to be sufficient to explain the observed infertility.
The high dose group P animals showed lack of viable sperm.
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
There was no adverse effect on the reproduction in low and mid dose animals.
GROSS PATHOLOGY (PARENTAL ANIMALS)
No abnormalities were observed in the examined organs, except atrophied tested in the high dose males.
HISTOPATHOLOGY (PARENTAL ANIMALS)
Atrophied tested in the high dose males were seen.
No change in litter size and livebirth index was noted in F1, F2 and F3 litters in low and high dose groups compared with control values.
BODY WEIGHT (OFFSPRING)
No change in body of pups in low and high dose groups weights was noted in F1, F2 and F3 litters in compared with control values.
GROSS PATHOLOGY (OFFSPRING)
No abnormalities were observed in the examined organs.
Reproduction data:
Control | Dietary level of Boric acid | Control | Dietary level of Boric acid | |||
Index | 34 mg/kg bw/d | 100 mg/kg bw/d | 34 mg/kg bw/d | 100 mg/kg bw/d | ||
P1 - F1A | P1 - F1B | |||||
Fertility index | 62.5 | 87.5 | 81.3 | 60 | 87.5 | 75 |
lactation index | 56.3* | 96.2 | 70.3* | 58.8 | 85.6* | 80.0* |
Live birth index | 98.4 | 96 | 97.2 | 99.1 | 99.4 | 100 |
P2 - F2A | P2 - F2B | |||||
Fertility index | 81.3 | 93.8 | 80 | 93.8 | 93.8 | |
lactation index | 48.3 | 79.2* | 92.1 | 81 | 98 | |
Live birth index | 97.8 | 100 | 98.6 | 99.4 | 97.9 | |
P3 - F3A | P3 - F3B | |||||
Fertility index | 68.8 | 100 | 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 | 99.5 | 97.9 | 100 | 99 | 98.8 |
* significantly higher than control
Effect on fertility: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 343 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
In a three generation study in rats groups of 8 males and 16 females were treated with boric acid equivalent to 0, 5.9, 17.5 and 58.8 mg boron/kg bw/day. The high dose P1-generation failed to produce litter. Also when females of that group were mated with untreated males they had no offspring, indicating that the female reproduction was affected. A decreased ovulation in the majority of ovaries examined in that group was mentioned not to be sufficient to explain the observed infertility since only ovaries of high dosed females were examined. However, gross necropsy revealed atrophied testes in all P1 males at 58.8 mg boron/kg bw/day. Based on the sterility in the highest dose group, the NOAEL for reproduction was found to be 100 mg/kg bw/d Boric acid in diet corresponding to 17.5 mg/kg bw Boron and 343 mg/kg bw/d for Sodium triacetoxyborohydride respectively.
Short description of key information:
Reproduction: NOAEL = 343 mg/kg bw/d (= 100 mg/kg bw Boric acid or 17.5 mg/kg bw/d for element Boron; 3-Generation study in rats)
Justification for selection of Effect on fertility via oral route:
Reliable published study, peer reviewed and already internationally used for risk assessment
Effects on developmental toxicity
Description of key information
Developmental toxicity: NOAEL = 428 mg/kg bw/d (= 125 mg/kg bw Boric acid or 21.8 mg/kg bw/d for element Boron (comp. OECD 414)
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication of a study performed equivalent to OECD guideline with the decomposition product boric acid
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- not specified
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazleton Research Products inc., Denver, PA, USA
- Age at study initiation: approx. 5 months
- Weight at study initiation: 2690 - 4380 g
- Housing: individually in stainless steel cages with mesh flooring
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow (No. 5322), Ralston Purina Co., St. Louis, MO, USA; ad libitum
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8 - 26.1
- Humidity (%): 47 - 89
- Photoperiod (hrs dark / hrs light): 12 / 12 (females), 10 / 14 (males) - Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- distilled/deionized
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
dose volume was adjusted daily.
VEHICLE
- Amount of vehicle (if gavage): 5 mL/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Assays (UVNIS spectroaxtry) conducted prior to dosing indicated that all formulations were within a range of 94-106% of the theoretinl concentrationa Formulations were used within the period of demcostrued stability.
- Details on mating procedure:
- - Impregnation procedure: artificial insemination
- Any other deviations from standard protocol: The study was performed in two replicates with two consecutive breeding days within each replicate
and 34 days between replicates. - Duration of treatment / exposure:
- Treatment: on gestational days 6 - 19
Termination: at day 30 of gestation - Frequency of treatment:
- Once daily on the mornings, 7 d/weeks
- Duration of test:
- 30 days (gestation days 0 - 30)
- Remarks:
- Doses / Concentrations:
62.5, 125 or 250 mg/kg bw
Basis:
actual ingested
Boric acid - Remarks:
- Doses / Concentrations:
10.9, 21.8 and 43.5 mg/kg bw
Basis:
actual ingested
Element Boron - No. of animals per sex per dose:
- 30
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on reults of preliminary toxicity study where nonpregnant female rabbits (2/group) were dosed with BA (0 or 275 mg/kg bw/day, po) using a dose volume of 5 mL/kg in distilled/deionized water.
- Maternal examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6-19, 25 and 30
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, at 2-3 days intervals
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 30
- Organs examined: liver, kidneys,uterus - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - External examinations: Yes: All per litter, including cleft palate
- Soft tissue examinations: Yes: All per litter, including sex determination
- Skeletal examinations: Yes: All per litter
- Head examinations: Yes: Half per litter
Litter size, number of dead foetuses and foetal weight were assessed. - Statistics:
- The doe or litter was considered the experimental unit for all statistical analyses . General Linear Models (GLM) procedures were applied for the analyses of variance (ANOVA) of maternal and fetal parameters . Prior to GLM analysis, an arcsinesquare root transformation was performed on all litter-derived percentage data and Bartlett's test for homogeneity of variance was performed on all data to be analysed by ANOVA . GLM analysis determined the significance of dose-response relationships and the significance of dose effects, replicate effects, and dose X replicate interactions . When ANOVA revealed a significant (p < 0 .05) dose effect, Dunnett's multiple comparison test compared exposed groups to control groups. One-tailed tests were used for all pairwise comparisons except maternal body and organ weights and fetal body weight. Nominal scale measures were analyzed by x² test for independence and by a test for linear trend on proportions. When a x² test showed significant groupwise differences, a one-tailed Fisher's exact probability test was used for pairwise comparisons of control and BA groups.
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
No treatment-related clinical signs of toxicity were observed during the study, except for vaginal bleeding noted in 2-11 does/day on gd 19-30 at the high dose; these does had no live fetuses on day 30. Vaginal bleeding was also observed in one female in the low-dose group and in one in the mid-dose group. Two maternal deaths occurred (one each at the low- and mid-dose), but were not treatment-related. Food intake was decreased relative to that of controls on treatment days 6-15 at the high dose, and was increased after treatment ceased on days 25-30 at the mid and high doses. Body weight on gd 9-30, weight gain on gd 6-19, gravid uterine weight, and number of corpora lutea per dam were each decreased in the high-dose group. After correction for gravid uterine weights, however, maternal body-weight gain was increased at both the mid-and high- doses. Treatment with boric acid did not affect absolute or relative liver weight. Relative, but not absolute kidney weight increased at the high dose; kidney histopathology was unremarkable. - Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- Boric acid
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 21.9 mg/kg bw/day (actual dose received)
- Based on:
- element
- Remarks:
- Boron
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- Boric acid
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 21.9 mg/kg bw/day (actual dose received)
- Based on:
- element
- Remarks:
- Boron
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Developmental effects were noted in the high dose group which consisted of a high rate of prenatal mortality (90% of implants/litter were reabsorbed compared with 6% in controls). Also, the percentage of pregnant females with no live fetuses was greatly increased (73% compared with 0% in controls), whereas the number of live fetuses per litter on day 30 was significantly reduced (2.3/litter compared with 8.8/litter in controls). Malformed live fetuses per litter increased significantly at the high dose, primarily due to the incidence of fetuses with cardiovascular defects, the most prevalent of which was interventricular septal defect (8/14 at high dose compared with 1/159 in controls). The incidence of skeletal malformations was comparable among groups. Relative to controls, the percentage of fetuses with variations (all types combined) was not significantly increased in any treated group, but the percentage with cardiovascular variations was significantly increased from 11% in controls to 64% in the high-dose group. Fetal body weights per litter at the high dose were depressed relative to control, but the difference was not statistically significant; however, this could have been due to the small sample size in the high-dose group. No developmental effects were found in the low- and mid-dose groups. - Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on increased resorptions and CVS malformations in surviving fetuses at 250 mg/kg bw/day
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Due to observed maternal and developmental effects at 125 mg/kg bw/d Boric acid, this dose corresponding to 21.8 mg/kg bw/d Boron was determined to be the NOAEL.
- Executive summary:
Developmental toxicity of Boric acid was evaluated in a GLP study performed equivalent to OECD guideline 414, where groups of 30 New Zealand White) rabbits were administered boric acid once daily by gavage at doses corresponding to 0, 10.9, 21.9 and 43.8 mg boron/kg bw/day during major organogenesis on GD 6-19. The rabbits exposed to 43.8 mg boron/kg bw/day on gestation day 6-19 revealed decreased food intake during treatment, relative but not absolute kidney weight increase and vaginal bleeding. At the highest dose, prenatal mortality was increased (90% resorption/litter versus 6% in controls). In this dose group the number of live fetuses available for evaluation where dramaticall decreased compared to live fetuses in the other groups. Additionally, the resorption rate was disproportionally high (95%) and an increased incidente of malformed live foetuses/litter was observed primarily due to cardiovascular effects. Based on these results, the NOAEL for maternal and developmental toxicity was 125 mg/kg bw/d boric acid corresponding to 21.8 mg/kg bw/d Boron, respectively.
Reference
Maternal toxicity:
Boric acid (mg/kg bw/d) | |||||
0 | 62.5 | 125 | 250 | ||
No. pregnant at euthanization | 18 | 23 | 20 | 22 | |
No. of live litters | 18 | 23 | 20 | 6 | |
No. of live fetuses | 159 | 175 | 153 | 14 | |
Maternal weight change (g) | Treatment period (GD 6 to 19) | 93 ± 30* | 132 ± 40 | 97 ± 51 | -137 ± 42** |
Gestation period (GD 0 to 30) | 357 ± 69* | 493 ± 51 | 543 ± 63** | 226 ± 35 | |
Corrected gestation wt. gain | -205 ± 78* | -52 ± 63 | 40 ± 57** | 165 ± 40** | |
Gravid uterine wa (g)a | 562 ± 40* | 504 ± 26 | 502 ± 28 | 62 ± 18** | |
Maternal liver weight (% bw) | 2.56 ± 0.13 | 2.8 ± 0.09 | 2.78 ± 0.08 | 2.87 ± 0.09 | |
Maternal kidney weight (% bw) | 0.46 ± 0.02 | 0.46 ± 0.01 | 0.47 ± 0.01 | 0.51 ± 0.01** | |
Renal pathology | 0/18 | 2/23 | 0/20 | 1/22 | |
Relative food consumption (g/kg/day) | Pretreatment period (GD 0 to 6) |
48.1 ± 1.7 | 48.0 ± 1.8 | 48.9 ± 2.4 | 46.4 ± 1.5 |
Treatment period (GD 6 to 19) | 38.8 ± 1.7* | 40.0 ± 2.0 | 38.7 ± 2.3 | 26.6 ± 2.2** | |
Posttreament (GD 19-25) | 36.9 ± 2.5* | 37.0 ± 2.6 | 40.0 ± 3.1 | 44.9 ± 2.2 | |
Posttreament (GD 25-30) | 24.5 ± 3.0 | 30.9 ± 2.1 | 33.9 ± 1.9** | 41.9 ± 1.6** |
* p < 0.05, linear trend. .
** p < 0.05, Dunnett's teat.
Developmental effects:
Boric acid (mg/kg bw/d) | |||||
0 | 62.5 | 125 | 250 | ||
No. implantation sites per litter (a) | 9.5 ± 0.8 | 26.1 ± 3.8 | 8.3 ± 0.5 | 8.6 ± 0.7 | |
% Resorptions per litter (a) | 6.3 ± 2.4* | 5.9 ± 1.9 | 7.7 ± 2.1 | 89.9 ± 5.0** | |
% Litters with one or more resorptions | 39 | 39 | 45 | 95*** | |
% Litters with 100% resorptions | 0 | 0 | 0 | 73*** | |
No. live fetuses per litter (b) | 8.8 ± 0.8* | 7.6 ± 0.6 | 7.7 ± 0.5 | 2.3 ± 0.8** | |
Average fetal body wt (g) per litter (b) | 44.8 ± 1.5 | 46.5 ± 1.4 | 45.7 ± 1.2 | 41.1 ± 2.7 | |
All malformations | % Fetuses per litter (b) | 25.5 ± 5.8* | 26.1 ± 3.8 | 30.4 ± 6.3 | 80.6 ± 16.3** |
%Litters | 72 | 78 | 75 | 83 | |
External malformations | % Fetuses per litter (b) | 0.8 ± 0.8* | 1.4 ± 1.0 | 1.0 ± 1.0 | 11.1 v 8.2** |
%Litters | 6 | 9 | 5 | 33 | |
Skeletal malformations | % Fetuses per litter (b) | 19.9 ± 5.4 | 19.9 ± 4.0 | 24.3 ± 6.4 | 38.9 ± 20.0 |
%Litters | 61 | 65 | 55 | 50 | |
Visceral malformations | % Fetuses per litter (b) | 7.3 ± 1.9* | 5.9 ± 2.0 | 7.4 ± 2.0 | 80.6 ± 16.3** |
%Litters | 50 | 35 | 45 | 83 | |
Cardiovascular malformations | % Fetuses per litter (b) | 2.7 ± 1.6* | 3.1 ± 1.5 | 4.2 ± 1.3 | 72.2 ± 16.5** |
%Litters | 17* | 22 | 35 | 83*** | |
All variations | % Fetuses per litter (b) | 67.7 ± 7.2 | 54.8 ± 5.1 | 40.4 ± 5.2 | 86.1 ± 9.0 |
%Litters | 94 | 100 | 90 | 100 | |
Cardiovascular variations | % Fetuses per litter (b) | 10.6 ± 5.5* | 5.7 ± 1.8 | 7.2 ± 2.5 | 63.9 ± 17.4** |
%Litters | 44 | 35 | 35 | 83 |
a) Includes all dams pregnant at euthanization; litter size is number of implantation sites per dam; mean ± SEM.
b) Includes only dams with live fetuses; litter size is number of live fetuses per dam; mean ± SEM.
* p < 0.05, linear trend. .
** p < 0.05, Dunnett's teat.
*** p< 0.05, Fisher’s exact test.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 428 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rabbit
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Developmental toxicity of Boric acid was evaluated in a GLP study performed equivalent to OECD guideline 414, where groups of 30 New Zealand White) rabbits were administered boric acid once daily by gavage at doses corresponding to 0, 10.9, 21.9 and 43.8 mg boron/kg bw/day during major organogenesis on GD 6-19. The rabbits exposed to 43.8 mg boron/kg bw/day on gestation day 6-19 revealed decreased food intake during treatment, relative but not absolute kidney weight increase and vaginal bleeding. At the highest dose, prenatal mortality was increased (90% resorption/litter versus 6% in controls). In this dose group the number of live fetuses available for evaluation where dramaticall decreased compared to live fetuses in the other groups. Additionally, the resorption rate was disproportionally high (95%) and an increased incidents of malformed live foetuses/litter was observed primarily due to cardiovascular effects. Based on these results, the NOAEL for maternal and developmental toxicity was 125 mg/kg bw/d boric acid corresponding to 21.8 mg/kg bw/d Boron and 428 mg/kg bw/d for Sodium triacetoxyborohydridee, respectively.
Justification for selection of Effect on developmental toxicity: via oral route:
Reliable published GLP study comparable to OECD 414, peer reviewed and already internationally used for risk assessment
Justification for classification or non-classification
The available data on toxicity to reproduction of the test substance do not meet the criteria for classification Repr. 1B (according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.
No information is available on effects via lactation.
Additional information
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