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EC number: - | CAS number: -
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental 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:
- Unnamed
- Year:
- 1 989
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Aluminium hydroxide
- EC Number:
- 244-492-7
- EC Name:
- Aluminium hydroxide
- Cas Number:
- 21645-51-2
- Molecular formula:
- AlH3O3
- IUPAC Name:
- aluminum trihydroxide
Constituent 1
- Specific details on test material used for the study:
- Aluminum hydroxide, analytical grade, was provided by the Merck Company (Darmstadt, FRG).
Test animals
- Species:
- mouse
- Strain:
- Swiss
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Panlab, Barcelona, Spain
- Age at study initiation: sexually mature
- Weight at study initiation: 28-32 g
- Fasting period before study: no
- Housing: Mice were individually housed in environmentally controlled rooms
- Diet: ad libitum, Panlab certified chow (Barcelona, Spain).
- Water: ad libitum, demineralized water
- Acclimation period: not specified
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2° C
- Humidity (%): 50±10%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hour light-dark-photocycle
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
- Pregnant mice were given by gavage a daily dose of aluminum hydroxide dissolved in distilled water - Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused: Five females were placed with two males in separated cages until copulation was detected. Finding of sperm indicated copulation and the day of detection was designated day 0 of pregnancy.
- M/F ratio per cage: 2/5
- Proof of pregnancy: Finding of sperm referred to as day 0 of pregnancy - Duration of treatment / exposure:
- Gestational days (GD) 6-15
- Frequency of treatment:
- daily
- Duration of test:
- Up to GD 18
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 66.5 mg/kg bw/day
- Remarks:
- corresponding to 23 mg aluminium/kg bw/day.
- Dose / conc.:
- 133 mg/kg bw/day
- Remarks:
- corresponding to 46 mg aluminium/kg bw/day.
- Dose / conc.:
- 266 mg/kg bw/day
- Remarks:
- corresponding to 92 mg aluminium/kg bw/day.
- No. of animals per sex per dose:
- 20 mated females per dose group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Rationale for animal assignment:
The mated females were distributed randomly in four groups
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All animals were observed daily for appearance and behavior.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All animals were observed daily for clinical signs of toxicity.
BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were computed for the pretreatment, treatment, and posttreatment periods from daily records.
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Food consumption was computed for the pretreatment, treatment, and posttreatment periods from daily records.
WATER CONSUMPTION AND COMPOUND INTAKE: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 18
- Organs examined: The heart, lungs, spleen, liver, kidneys, and brain were weighed for organ/body weight comparisons. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included: Uteri were removed, and the number of total implantations and live, dead and resorbed fetuses were recorded.
- Gravid uterus weight: No data
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Blood sampling:
- - Plasma: No
- Serum: No - Fetal examinations:
- - External examinations: Yes, Following body weight, body length and sex determinations, each fetus was externally examined for gross abnormalities.
- Soft tissue examinations: Yes, More than half of viable fetuses evaluated for skeletal abnormalities, the remainder were fixed in Bouin's fluid and examined for visceral anomalies
- Skeletal examinations: Yes, More than half of the viable fetuses were assigned for the evaluation of skeletal abnormalities after staining with Alizarin Red S
- Head examinations: No data - Statistics:
- The litter was considered the basic unit for statistical analysis. Maternal body weight gain and food consumption were evaluated by analysis of variance with differences among groups determined by Student's t test or Mann-Whitney U test. Nonparametric data were analyzed by the Kruskal-Wallis test.
Because of the very few number of malformations or developmental variations, the incidence was not analyzed statistically. The level of significance for all analysis was P<0.05.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No aluminum hydroxide-related clinical signs of toxicity were observed in the pregnant mice of any group.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- No aluminum hydroxide-related deaths were observed in the pregnant mice of any group.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Maternal toxicity was also assessed by examining the changes in maternal weight gain and food consumption. No significant differences between the aluminum hydroxide-treated groups and the control group were noted.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Endocrine findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- Upon sacrifice, the absolute and relative weights of heart, lungs, spleen, liver, kidneys and brain were similar between treated and control groups.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No gross postmortem effects attributed to the treatment were recorded.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- The administration of aluminum hydroxide by oral gavage daily from day 6 to 15 of gestation had no recognizable adverse effects on the number of implantations and number of resorptions.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- The administration of aluminum hydroxide by oral gavage daily from day 6 to 15 of gestation had no recognizable adverse effects on the number of resorptions.
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- The administration of aluminum hydroxide by oral gavage daily from day 6 to 15 of gestation had no recognizable adverse effects on the number of resorptions.
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- The administration of aluminum hydroxide by oral gavage daily from day 6 to 15 of gestation had no recognizable adverse effects on the number of live and dead fetuses.
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- not specified
- Other effects:
- not specified
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 266 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: No adverse effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 92 mg/kg bw/day
- Based on:
- other: Aluminum content
- Basis for effect level:
- other: No adverse effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Body weights of fetuses removed on day 18 of gestation were not affected by any dose of aluminium hydroxide.
- Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- The administration of aluminum hydroxide by oral gavage daily from day 6 to 15 of gestation had no recognizable adverse effects on the number of live and dead fetuses.
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- The administration of aluminum hydroxide by oral gavage daily from day 6 to 15 of gestation had no recognizable adverse effects on the fetal sex ratio.
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- Body weights and body lengths of fetuses removed on day 18 of gestation were not affected by any dose of aluminium hydroxide.
- Anogenital distance of all rodent fetuses:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Description (incidence and severity):
- No remarkable external malformations were found in any group.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- No remarkable skeletal abnormalities were found in any group.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- No remarkable internal soft-tissue defects were found in any group.
Effect levels (fetuses)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 266 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 92 mg/kg bw/day
- Based on:
- other: Aluminum content
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Any other information on results incl. tables
Table 1: Maternal Relative Organ Weights of Mice Receiving Aluminum Hydroxide on Days 6 Through 15 of Gestation
Dose (mg/kg/day) | ||||||||
0 | 66.5 | 133 | 266 | |||||
mean | SE | mean | SE | mean | SE | mean | SE | |
Heart | 0.31 | 0.01 | 0.35 | 0.03 | 0.34 | 0.03 | 0.35 | 0.02 |
Lungs | 0.56 | 0.04 | 0.61 | 0.05 | 0.46 | 0.04 | 0.52 | 0.07 |
Spleen | 0.23 | 0.02 | 0.25 | 0.03 | 0.20 | 0.01 | 0.27 | 0.04 |
Liver | 4.39 | 0.16 | 4.82 | 0.17 | 4.25 | 0.27 | 4.26 | 0.28 |
Kidneys | 0.81 | 0.03 | 0.89 | 0.07 | 0.88 | 0.06 | 0.89 | 0.09 |
Brain | 0.79 | 0.03 | 0.77 | 0.09 | 0.87 | 0.07 | 0.87 | 0.10 |
Table 2: Effects of Aluminum Hydroxide Administered to Mice on Days 6 Through 15 of Gestation
Dose (mg/kg/day) | ||||||||
0 | 66.5 | 133 | 266 | |||||
mean | SE | mean | SE | mean | SE | mean | SE | |
No. of litters | 20 | - | 18 | - | 19 | - | 18 | - |
No. of total implants/litter | 11.50 | 0.70 | 12.40 | 0.70 | 11.80 | 0.70 | 11.10 | 1.00 |
No. of resorptions/litter | ||||||||
early | 0.40 | 0.20 | 3.00 | 1.70 | 2.40 | 1.10 | 1.30 | 1.10 |
late | 0.00 | 0.00 | 0.10 | 0.20 | 0.10 | 0.30 | 0.10 | 0.30 |
No. of live fetuses/litter | 11.10 | 0.70 | 9.40 | 1.10 | 9.20 | 1.10 | 9.80 | 1.20 |
No. of dead fetuses/litter | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
Sex ratio (M:F)/litter | 1.34 | 0.25 | 0.96 | 0.07 | 1.02 | 0.17 | 1.13 | 0.25 |
Fetal body weight (g) | 1.40 | 0.02 | 1.41 | 0.03 | 1.43 | 0.02 | 1.42 | 0.03 |
Fetal body length (cm) | 3.11 | 0.02 | 3.11 | 0.03 | 3.24 | 0.03 | 3.10 | 0.03 |
Applicant's summary and conclusion
- Conclusions:
- In a prenatal developmental toxicity study in Swiss mice, aluminum hydroxide did not induce maternal toxicity up to 266 mg/kg bw/day. Neither embryotoxicity nor teratogenicity was detected in any treatment group. The no observed adverse effect level (NOAEL) for maternal and developmental effects is therefore >266 mg/kg bw/day (corresponding to 92.01 mg Al/kg bw/day).
- Executive summary:
In a developmental toxicity study (similar to OECD TG 414), aluminum hydroxide was orally administered to groups of 20 pregnant female Swiss mice/dose by gavage at dose levels of 0, 66.5, 133 and 266 mg/kg bw/day in distilled water from days 6 through 15 of gestation.
There were no treatment-related effects in mortality, clinical signs, body weight or maternal developmental parameters observed. The maternal NOAEL is therefore considered to be >266 mg/kg bw/day (corresponding to 92.01 mg Al/kg bw/day).
In addition, there were no treatment-related effects in developmental parameters in offspring. The developmental NOAEL is therefore considered to be >266 mg/kg bw/day (corresponding to 92.01 mg Al/kg bw/day).
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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