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EC number: 215-200-5 | CAS number: 1312-81-8
- 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:
- one-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:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Basic data given, but critical details for the evaluation of the study,as standard devialtion and variation in effects and their relation to historical control data are missing. Statisitcal analysis for some endpoints did not take into account litter effects.
Data source
Reference
- Reference Type:
- publication
- Title:
- Neurodevelopmental effects of lanthanum in mice
- Author:
- Briner, W. et al.
- Year:
- 2 000
- Bibliographic source:
- Neurotoxicology and Teratology 22: 573-581
Materials and methods
- Principles of method if other than guideline:
- No guideline mentioned: Mice were exposed to Lanthanum chloride in drinking water at 0, 125, 250, and 500 mg/L concentration prior to conception, during gestation, and until 30 days postnatally.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Lanthanum chloride, anhydrous
- EC Number:
- 233-237-5
- EC Name:
- Lanthanum chloride, anhydrous
- Cas Number:
- 10099-58-8
- Molecular formula:
- Cl3La
- IUPAC Name:
- lanthanum trichloride
- Reference substance name:
- Lanthanum chloride
- IUPAC Name:
- Lanthanum chloride
- Details on test material:
- - Name of test material (as cited in study report): Lanthanum chloride
- Molecular formula (if other than submission substance): LaCl3·7H2O
- Analytical purity: no data
Constituent 1
Constituent 2
Test animals
- Species:
- mouse
- Strain:
- Swiss Webster
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 4-6 weeks
- Housing: 10 per cage
- Access to food and water: ad libitum
ENVIRONMENTAL CONDITIONS
- Photoperiod: 14 h:10 h (light:dark cycle)
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- The female mice were exposed to lanthanum chloride in distilled drinking water under one of four doses (0, 125, 250, and 500 mg/L corresponding to 0, 0.34, 0.67, and 1.35 mM respectively).
- Details on mating procedure:
- Impregnation procedure: cohoused, no further information available
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- The mice were exposed for 14 days and then mated with males of the same age and strain. Exposure to lanthanum continued through gestation, parturition, and the postnatal period until day 30. The day of birth was designated postnatal day 0.
- Frequency of treatment:
- Drinking water ad libitum
- Details on study schedule:
- Mice were exposed for 14 days and then mated with males of the same age and strain. Exposure to lanthanum continued through gestation, parturition, and the postnatal period for the dams and pups until day 30. The day of birth was designated postnatal day 0.
For all the assessments the experimenter was blind to the treatment group of the animals. All experimenters were trained to criterion. Testing was done during the same time each day and the order of testing was random.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 125, 250, and 500 mg/L; 0, 0.34, 0.67, and 1.35 mM, respectively
Basis:
nominal in water
- No. of animals per sex per dose:
- Dams: Control: 10; 125 and 250 mg/L: 7; 500 mg/L: 12
- Control animals:
- yes, concurrent no treatment
- Positive control:
- no data
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: no data - Sperm parameters (parental animals):
- no males exposed
- Litter observations:
- STANDARDISATION OF LITTERS: no data
PARAMETERS EXAMINED
1) Developmental assessment:
Behavioral and neurologic assessments were made from age 4 to 20 days including the development of
- swimming behavior (every day)
- ear and eye opening (every day)
- weight gain (at 4, 8, 12, and 16 days of age).
Swimming was scored by dropping the animals into a pool of warm water (approx. 33° C) from a height of 6 inches.
Swimming behavior was scored within 10 s to avoid fatigue.
- a score of 0 was assigned if the animal was not able to keep its nose out of the water
- a score of 1 was assigned if the nose was out of the water
- a score of 2 was assigned if the nose and half of the head to the middle of the ear was out of the water
- a score of 3 was assigned if more than half of the head was out of the water
- a score of 4 was assigned if the animals exhibited adult swimming behavior by kicking with the hind limbs while keeping the forelimbs extended forward.
2) Neurological assessment
Between 30 and 32 days of age the animals were assessed with a modified version of a functional observational battery according to O´Donoghue (1996). Modifications consisted of the omission of the open-field component because pilot work did not suggest an effect of lanthanum exposure. - Postmortem examinations (parental animals):
- no data
- Postmortem examinations (offspring):
- Brain chemistry
At 59 to 60 days of age the animals were killed with chloroform and weighed, and brains were removed, which were weighed and frozen. Lipid, protein, and lanthanum content of the brains were determined. - Statistics:
- The litter was the unit of analysis for only part of the data derived from this study. For continuous variables (weights, swimming, lanthanum content, protein content) data were collapsed across litters and analyzed as by analysis of variance (ANOVA). For categorical data one subject was selected at random from each litter and analyzed with the chi-squared test. Gender was not used as an independent variable because pilot studies found no differences between the sexes. Follow-up analytic comparisons were done to determine group differences from control when appropriate.
- Reproductive indices:
- no data
- Offspring viability indices:
- no data
Results and discussion
Results: P0 (first parental generation)
Details on results (P0)
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Remarks:
- reproduction
- Effect level:
- 40 mg/kg bw/day (nominal)
- Sex:
- female
- Basis for effect level:
- other: recalculated value from 500 mg/L drinking water based on a daily water consumption of 200 mL/kg bw/d no effects up to and including the highest dose tested
Results: F1 generation
Details on results (F1)
Litter size did not differ significantly between the groups [F(3, 32) = 0.33, p = 0.8 nor did the mortality rate of the pups due to cannibalism or
death of unknown cause [F(3, 32) = 0.77, p = 0.52].
CLINICAL SIGNS (OFFSPRING)
The general health and constitution of the offspring did not differ between the groups.
Eye opening:
The eye opening was delayed for the 125- and 250-mg/L groups, when compared to control. This was apparent at 14 days of age for both the 125- and 250-mg/L groups with a trend toward significance at 15 days postnatally for the 250-mg/L group. The 500-mg/L group were more similar to the
control group with regard to eye opening. Prior to and after those ages variance in eye opening was negligible. As there was no dose response and the high dose animals were comparable to controls, the effects are not considered treatment related.
Ear opening:
There was a trend for ear opening to be delayed for the 125- and 250-mg/L lanthanum groups at 13 days of age. Follow-up analysis found a significant difference between the control and 250-mg/L group. The 500-mg/L group appeared to behave more similarly to control. Prior to and after those ages differences in ear development were not significant. As there was no dose response and the high dose animals were comparable to controls, the effects are not considered treatment related.
BODY WEIGHT (OFFSPRING)
Weight gain did not differ in a statistically significant manner among the treatment groups although there was a nonsignificant trend for the 250- and 500-mg/L lanthanum-exposed groups to gain weight less readily than the other groups.
SEXUAL MATURATION (OFFSPRING)
No data given
ORGAN WEIGHTS (OFFSPRING)
The brain weight of the litters did differ between groups with the 500-mg/L group being statistically significantly different from the control group [F(3, 31) = 5.11, p = 0.006]. The brain-to-body-weight ratios did not differ between groups. Brain lanthanum, protein, and lipid content did not differ between treatment groups. However, there was a statistically significant correlation between brain lanthanum and protein content [r(19) = 0.49, p < 0.05]. Although being statistically significant, the effects described above are not of toxicological significance.
GROSS PATHOLOGY (OFFSPRING)
no data given
HISTOPATHOLOGY (OFFSPRING)
no data given
OTHER FINDINGS (OFFSPRING)
Emergence of walking behaviour
The emergence of walking behavior was delayed at 5 and 6 days postnatally for the 250-mg/kg group for both 5 and 6 days postnatally. The other
groups did not differ from control. After this age there was not a statistically significant difference between any of the groups. The authors did not analyse the relation to body weight of this effect. As the effect was only observed in the mid dose group and not in the low and high dose group, the findings are not considered treatment related.
Swimming development
A trend for swimming development to be delayed was reported by the authors for postnatal days 6 through 14 with statistically significant effects for the 250-mg/L and 500-mg/L groups. However, the graph depicted in the publication did not indicate a significant effect at the 500 mg/L dose level. According to the graph there was no dose response as well with regard to effect size. Furthermore the statisitcal analysis for this endpoint did not take into account the litter and may therfore not be appropriate. The reported effects on swimming behavior can therefore not be regarded as treatment related effects in the opinion of the applicant.
Neurological assessment (30-32 days of age)
Touch Response performance was characterized by the 125- and 250-mg/L lanthanum-exposed groups scoring more frequently for jerking toward the object (score 3) than the control group. However, according to the graphical depiction more animals inthe controls had a score 4 (agressive or violent reaction with or without vocalization. The 250-mg/L group also exhibited more freezing or turning to the opposite side (score 2). The
500-mg/L group reacted in a manner more similar to the control group (turning toward object or walking away). The variation in the responses is and standard deviation as well as historicall control data are also not given. As there was again no dose response and the low and high dose group were similar to controls, this effect cannot be regarded as treatment related.
Visual Placing Response performance was characterized by proportionately more mice in the 500-mg/L group scoring 1 for early vigorous extension or placing before vibrissae contact. The 125- and 250-mg/L groups scored 2 more frequently (placing after slight vibrissae contact), but according to the grpahical depiction the control group animals also scored 1 and 2, but in a slightly different proportion. No indication of the varialtionand standard deviation of the responses are given and also no indications of the historical control values. In the absence of this infomation the reported effects remain of questionable toxicological significance. As also no dose response in the pattern of reaction was observed, the applicant is of the opinion that the reported effects cannot be clearly related to the treatment.
The neurological effects described above usually occured at the low and medium dose level. Usually, high dose animals appeared to behave similar to controls. No clear dose response was observed for any of the reported effects. It can therfore be concluded that no clearly test substance related effects were observed in this study.
Effect levels (F1)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- developmental
- Generation:
- F1
- Effect level:
- 40 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: recalculated value from 500 mg/L drinking water based on a daily water consumption of 200 mL/kg bw/d
- Dose descriptor:
- NOAEL
- Remarks:
- neurotoxicity
- Generation:
- F1
- Effect level:
- 40 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: recalculated value from 500 mg/L drinking water based on a daily water consumption of 200 mL/kg bw/d no clearly test substance related effect on neurobehavioral endpoints. (Original data: test substance was LaCl3*7H2O)
- Dose descriptor:
- NOAEL
- Remarks:
- neurotoxicity
- Generation:
- F1
- Effect level:
- 500 mg/L drinking water
- Sex:
- male/female
- Basis for effect level:
- other: Converted to lanthanum trichloride anhydrous!
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Exposure of female and offspring mice to up to 500 mg/L of lanthanum chloride in drinking water from 14 days premating throughout the postnatal period did not result in any clearly treatment related effects. Female mating behavoir and outcome was reportedly not affected by the treatment. Although the authors have reported some behavioral changes in some dose groups, the reported effects did not show a dose response and the effects as reported cannot be attributed to the treatment.
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