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Description of key information

Acute toxicity: oral
A K2 acute oral toxicity test was performed in male and female Sprague Dawley rats according to a guideline similar to OECD Guideline 401 (Cochran, 1950). This study was selected as key study, as the other available information came from a secondary source (considered K4)
Acute toxicity: inhalation:
no study available for this endpoint
Acute toxicity: dermal:
A K1 acute dermal toxicity test was performed in male and female Wistar rats following the OECD 402 Guideline (Bradshaw, 2013).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well documented, scientifically sound study with methods similar to OECD 401 with the following deviations: The number of deaths at each dose were not reported; the specific doses (mg/kg) were not provided; individual clinical observations, body weights, pathology were not reported; sex of the animals was not provided
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
The number of deaths at each dose were not reported; the specific doses (mg/kg) were not provided; individual clinical observations, body weights, pathology were not reported; sex of the animals was not provided
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: adult
- Weight at study initiation: between 200 and 300 g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
Animals were maintained in air conditioned rooms.

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% suspension

Doses:
The suspension was given in single doses by stomach tube. No further information on doses provided.
No. of animals per sex per dose:
32 rats in total
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: All animals were observed for 10 days. An initial group of animals receiving the test substance were kept for 30 days to verify that if any significant mortality occurred after the tenth day.
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
Statistics:
The LD50 values were obtained from ten day mortality data by using the log-probability method.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: i.e. 4400 mg La/kg bw
Mortality:
No further details reported. No sex differences were noted.
Clinical signs:
No further details reported except that lanthanum acetate was found to be the least toxic of several lanthanum compounds tested (lanthanum chloride, lanthanum ammonium nitrate, lanthanum nitrate, lanthanum oxide and lanthanum sulfate.
Body weight:
No data
Gross pathology:
No data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 was calculated to be 10000 mg compound/kg bw (i.e. 4400 mg La/kg bw)
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
10 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012/10/31 - 2012/11/21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP conditions according to with OECD Guideline No. 402 and EU Method B3.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 200 grams minimum
- Fasting period before study: No, free access to food and water was allowed throughout the study.
- Housing: The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of up to four, by sex, for the remainder of the study.
- Diet: Free access to food was allowed throughout the study.
- Water: Free access to water was allowed throughout the study.
- Acclimation period: 5 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 25 degrees Celsius
- Humidity (%): 30 – 70%
- Air changes (per hr): At least 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of light/12 hours of dark
Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- % coverage: Approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin and surrounding hair were wiped with cotton wool moistened with arachis oil BP to remove any residual test item.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Constant volume or concentration used: Yes, 2000 mg/kg bw
- For solids, paste formed: Yes, an appropriate amount of test item to achieve a dose level of 2000 mg/kg was moistened with arachis oil BP.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five male and five females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to application on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: At the end of the study the animals were killed by cervical dislocation and gross necropsies conducted.
- Other examinations performed: clinical signs and dermal reactions
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
One female showed bodyweight loss during the first week but expected bodyweight gain during the second week. One other female showed expected gain in bodyweight during the first week but bodyweight loss during the second week. The remaining animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No erythema, eschar or oedema were noted throughout the study.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 was found to be greater than 2000 mg/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute toxicity: oral

Cochran et al. (1950) performed an acute oral toxicity study (gavage) in Sprague-Dawley rats similar to the OECD 401 test guideline, using a 50% suspension. After exposure to a single dose, all animals (32 in total) were observed for 10 days. An LD50 value of 10000 mg/kg bw (or 4400 mg La/ kg bw) was determined for male and female rats. This study is chosen as key study.

A K4 study based on a secondary source (Lewis 1995) from which the original reference is not available indicated an LD50 value of 32700 mg/kg bw.

Acute toxicity: inhalation

No data are available for this endpoint. However, no further testing is needed as 2 routes of exposure are already covered, according to REACH regulation (column 2, annex VIII, section 8.5). Furthermore, the substance is hygroscopic and forms aggregates. Therefore this study is not justified.

 

Acute toxicity: dermal

Bradshaw (2013) performed an acute dermal toxicity study (limit test) in Wistar rats similar to the OECD 402 test guideline and EU Method B.3, using a semi-occlusive cover. After 24h of exposure to a single dose (2000 mg/kg bw), all animals (5 males, 5 females) were observed for 14 days. No mortality occurred and no signs of systemic toxicity were observed. Therefore LD50 was defined to be higher than 2000 mg/kg bw for male and female rats.


Justification for selection of acute toxicity – oral endpoint
Only one K2 study available for this endpoint.

Justification for selection of acute toxicity – dermal endpoint
Only one K1 study available for this endpoint

Justification for classification or non-classification

Based on the results of the acute oral and dermal toxicity study and according to the criteria of the DSD and CLP Regulation, lanthanum acetate should not be classified as an acute oral or dermal toxicant.

No data were available to decide on the classification for the inhalation route.