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EC number: 692-448-4 | CAS number: 170621-28-0
- 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:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 12 Oct 2014 - 16 Mar 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- 1995
- Deviations:
- yes
- Remarks:
- No analytic was performed as the test substance is a poor soluble inorganic substance, that is stable under the conditions. The test material was freshly prepared every day.
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- National(CFDA) GLP certificate
- Limit test:
- no
Test material
- Reference substance name:
- divanadium(5+) dialuminium(3+) magnesium(2+) nonaoxidandiide
- EC Number:
- 692-448-4
- Cas Number:
- 170621-28-0
- Molecular formula:
- Mg2xAl2xVyOz
- IUPAC Name:
- divanadium(5+) dialuminium(3+) magnesium(2+) nonaoxidandiide
- Test material form:
- solid: particulate/powder
- Details on test material:
- light yellow
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: Experimental Animal Center of Academy of Military Medical Sciences
- Females nulliparous and non-pregnant: yes
- Age at study initiation: (P) x 10-11wks
- Weight at study initiation: (P) Males: 317.9-359.8 g; Females: 218.7-270.1 g
- Fasting period before study: No
- Housing:The rats were housed five of one sex per cage at treatment before mating and after mating (only males). The pregnant animals were single-housed after mated. Animals were mated in the ratio of 1:1 (Male to Female) during the mating period.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25°C
- Humidity (%): 40-70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light):12 hrs dark/12 hrs light
IN-LIFE DATES: from 22 Dec 2014 to 13 Feb 2015
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:The test item formulations were freshly prepared every day immediately prior to application.
Appropriate amounts of the test item were weighted into a tared glass vial on a suitable precision balance and the vehicle (corn oil) was added to obtain the designed final concentration of the test item formulations. Homogeneity of the test item in the vehicle was maintained by vortexing the prepared suspension thoroughly before administration. The vehicle (corn oil) was also used as the control item.
VEHICLE
- Justification for use and choice of vehicle (if other than water): Corn oil is frequently used as a suitable vehicle in animal experiment when the solubility of test article is low in water. Moreover, corn oil has been proposed as a suitable vehicle by the OECD (OECD Guidelines for Testing of Chemicals 421Reproduction/Developmental Toxicity Screening Test (Adopted 24, July, 1995). Sponsor has agreed to use corn oil as vehicle in this study.
- Concentration in vehicle: Not specified
- Amount of vehicle (if gavage): 0.4 mL /100g body weight
- Lot/batch no. (if required): QS130302011011
- Purity: according to the nactional guidance on maize oil (GB 19111-2003) - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: 14 days
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
- Further matings after two unsuccessful attempts: not specified
- After successful mating each pregnant female was caged (how): The pregnant animals were single-housed after mated
- Any other deviations from standard protocol: No - Analytical verification of doses or concentrations:
- no
- Remarks:
- No analytical need for poor soluble inorganic substance
- Duration of treatment / exposure:
- approximately 54 days for female (day14 pre-mating to day 4 post-partum )
28 days for male (day14 pre-mating and day14 of mating ) - Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- low dose (LD) group
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- medium dose (MD) group
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- high dose(HD) group
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Toxicological Information: LC50 (inhalation) > 5 mg/L; LD50 (dermal) > 2000 mg/kg body weight; LD50 (oral) > 2000 mg/kg body weight; no signs of toxicity at acute sublethal concentration;
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Once daily
- Cage side observations included: mortality/viability
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: Males and females were weighed at receiving, grouping, first day of dosing and weekly thereafter, and at termination. During pregnancy, females were weighed every 3 days and within 24 hours after parturition (day 0 or 1 post-partum) and day 4 post-partum.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals were killed at day 28 of dosing
- Maternal animals: Pregnant females animals were killed at day 4 post-partum, and non-pregnant females were killed 24-26 days after the last day of the mating period.
GROSS NECROPSY
- At the time of sacrifice or death during the study, the adult animals were examined macroscopically for any abnormalities or pathological changes. Special attention was paid to the organs of the reproductive system. The pregnancy status of the females was ascertained. The number of implantation sites, the counting of corpora lutea, and the number of absorbed fetus and dead fetus were recorded. Uteri that appear non-gravid should be further examined by 8% ammonium sulphide staining for 20 min to confirm the non-pregnant status with or without implantation.
HISTOPATHOLOGY / ORGAN WEIGHTS
Detailed histological examination was performed on the ovaries, uterus, testes and epididymides of the animals of the highest dose group and the control group. Examinations were not extended to the animals of other dosage groups, because no changes were seen in the highest dose group. The testes and epididymides of male adult and ovaries and uterus of female adult animals were weighed. The absolute organ weights and the relative organ weights on the basis of the body weight were calculated. The ovaries, uterus, testes, epididymides, accessory sex organs and all organs showing macroscopic lesions of all adult animals were preserved using Bouin’s fixative. - Postmortem examinations (offspring):
- SACRIFICE
Dead pups and pups killed at day 4 post-partum were examined externally for gross abnormalities. - Statistics:
- The numerical data obtained in body weight, food consumption, organ weight and relative organ weight were subjected to multiple comparison tests for statistical significance of difference. The data were analyzed for homogeneity of variance and the homogeneous data were subjected to one-way analysis of variance. If significant differences were observed among groups, group mean difference between the control group and the dose group was subjected to multiple comparison test by the Dunnet t test (for homogeneous data). The enumeration data were analyzed using chi-square Test. These statistics were performed with SPSS 18.0 software (p<0.05 was considered as statistically significant)
Individual animal data were provided. Additionally, all data were summarized in tabular form, showing for each test group the number of animals at the start of the test, the number of animals found dead during the test or killed for human reasons, the time of any death or human kill, the number of fertile animals, the number of pregnant females, the number of animals showing signs of toxicity, a description of the signs of toxicity observed, including time of onset, duration, and severity of any toxic effects, the types of histopathological changes, and all relevant litter data. - Reproductive indices:
- Copulation index (%) = (numbers of animals mated/number of animals paired) × 100%
Fertility index (%) = (numbers of pregant female animals/number of animals paired) × 100%
Gestation index (%) = (numbers of pregnant female animals with live pups born/number of pregnant animals) × 100%
Viability index (%) = (numbers of pups alive Day 4 of age/numbe of pups born alive) × 100%
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- 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
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No mortalities were observed in pregnant animals during the entire period of the study. All the parental animals mated successfully, and gave birth within 22 days of pregnancy. The number of animals with pregnancy period ≤21 days in LD group was significant reduced when compared to the control group (P<0.05), while no significant changes were noted in MD and HD groups (P>0.05). There were no significant changes observed in dams with live young born, dams with live young born at day 4 post-partum, number of corpora lutea/dam (mean) and number of implants/dam (mean) in treatment groups when compared to control group. No statistically significant difference was found in reproductive indices in treatment groups when compared to control group.
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects were observed
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No test item related clinical signs were observed in any pups during the 4 days post-partum.
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- For pups, 16 pups were born dead (R1014-F13 (control group), R2038-F19, R2042-F16 (low dose group), R3061-M7, R3064- M9, R3066-M6, R3071-M8, R3071-M9, R3071-M10, R3071-M11, R3071-F17 (intermediate dose group) and R4090-M5, R4090-F12, R4090-F13, R4090-F14, R4091-F15 (high dose group)) and 2 pups were dead at day 4 post-partum (R1018-F13 and R2044-M1). There were no significant differences in treatment groups were found in dead pups at birth when compared with control group.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- When compared with control group, no statistically significant differences were found in litter weight at birth (mean) (P>0.05) and litter weight at day 4 (mean) (P>0.05). There were significant reduction in pup weight at birth (mean), pup weight at day 4 (mean), in LD group when compared to control group, while no significant changes were found in MD and HD group. The significantly pup weight changes only noted in LD group was judged to be of no toxicological significance.
- Food consumption and compound intake (if feeding study):
- not examined
- 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
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No abnormal pups observed (P>0.05).
- Histopathological findings:
- not examined
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- When compared with control group, no statistically significant differences were found in live/dead pups/dam at birth (P>0.05), live/dead pups/dam at day 4 (P>0.05), sex ratio (m/f) at birth (P>0.05), sex ratio (m/f) at day 4 (P>0.05), abnormal pups (P>0.05), loss of offspring (pre-implantation, pre-natal/post-implantations, post-natal). There were significant reduction in pup body length at birth (mean) and pup tail length at birth (mean) in LD group when compared to control group, while no significant changes were found in MD and HD group.
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- > 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects were observed
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Any other information on results incl. tables
Results:
Table 1. Mean Relative Organ Weights to Body Weight
Group |
Sex |
n |
Testes/ Uterus |
|
Left |
Right |
|||
C |
M |
12 |
0.340±0.026 |
0.338±0.030 |
F |
9 |
0.232±0.042 |
||
LD |
M |
12 |
0.352±0.049 |
0.356±0.055 |
F |
11 |
0.276±0.043* |
||
MD |
M |
12 |
0.340±0.039 |
0.354±0.034 |
F |
10 |
0.265±0.035 |
||
HD |
M |
12 |
0.375±0.039* |
0.376±0.040* |
F |
11 |
0.246±0.043 |
Data showed as Mean ± SD.
Table 2. Tabulated summary report of effects on reproduction/development
Observations |
Values |
||||||||
Dosage (mg/kg) |
0 |
100 |
300 |
1000 |
|||||
Females achieving pregnancy (N) |
9 |
11 |
10 |
11 |
|||||
Conceiving days 1 - 5 (N) |
9 |
11 |
10 |
11 |
|||||
Conceiving days 6 -14 (N) |
0 |
0 |
0 |
0 |
|||||
Pregnancy ≤21 days (N) |
5 |
11* |
8 |
4 |
|||||
Pregnancy = 22 days (N) |
4 |
0 |
2 |
7 |
|||||
Pregnancy≥23 days (N) |
0 |
0 |
0 |
0 |
|||||
Pup weight at birth (mean±SD) |
7.17±0.76 |
6.83±0.67* |
7.19±0.62 |
7.09±0.70 |
|||||
Pup weight at day 4 (mean±SD) |
9.76±1.42 |
8.86±1.26* |
9.46±1.17 |
9.89±1.36 |
|||||
Pup body length at birth (mean±SD) |
51.65±1.51 |
51.07±1.92* |
51.76±1.17 |
51.88± 1.64
|
|||||
Pup tail length at birth (mean±SD) |
16.96±1.53 |
16.56±1.23* |
16.76±0.84 |
16.71± 1.28
|
* P<0.05, ** P<0.01
Applicant's summary and conclusion
- Conclusions:
- In a reliable study conducted according to OECD 421 and in compliance with GLP, administration of the test item at a dose of 1000 mg/kg bw/day did not reveal adverse effects. Thus, the No Observed Adverse Effect Level (NOAEL) of Aluminium Magnesium Vanadium Oxide was determined to be 1000 mg/kg body weight/day for reproduction/developmental toxicity screening in males and females.
- Executive summary:
Objective
The objective of this study was to assess the possible effects of the test item Aluminium Magnesium Vanadium Oxide on male, female fertility and embryofetal development in Sprague Dawley rats when administrated orally.
Study Design
The test item Aluminium Magnesium Vanadium Oxide was administered via gavage to groups of 5 male and 5 female Sprague Dawley rats, respectively at dose levels of 0 mg/kg bw/d (group C, corn oil only), 100 mg/kg bw/d (group LD), 300 mg/kg bw/d (group MD) and 1000 mg/kg bw/d (group HD). The test item was administrated daily during 14 days pre mating period and 14 days mating period in both male and female, during gestation period and up to post natal day 4 in females. Animals were mated in the ratio of 1:1(Male to female). The non-pregnant females were still dosed to the day 24~26 post-mating.
During the period of administration, clinical signs, body weights, food consumption, fertility and mating performance, organ weights, and microscopic examinations were recorded for all parental animals. Litter size, litter observation, body weights, length and abnormalities were recorded for the offspring.
Results
No animal died and no test item related clinical signs were observed during the study. No statistically or toxicological significant effect was observed on body weight, food consumption, organ weights, histopathology findings, mating performanceand fertility, pregnancy and litter parameters in the study.
Conclusion
Based on the data generated from this study, the No Observed Adverse Effect Level (NOAEL) of Aluminium Magnesium Vanadium Oxide is 1000 mg/kg body weight/day for reproduction/developmental toxicity screening in males and females.
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