Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31 October 2012 - 21 November 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Lanthanum trihydroxide
EC Number:
238-510-2
EC Name:
Lanthanum trihydroxide
Cas Number:
14507-19-8
Molecular formula:
H3LaO3
IUPAC Name:
lanthanum(3+) trihydroxide
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Description: Yellow powder
Storage Conditions: Room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: RccHan:WIST.
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: At the start of the study the animals weighed at least 200 g. The weight variation did not exceed ± 20 % of the mean weight for each sex, with the exception of on male, which was heavier than all the others.
- Fasting period before study: No.
- Housing: The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes, individually during the exposure period and in groups of up to four, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): ad libitum access to rodent diet.
- Water (e.g. ad libitum): Free access to mains drinking water.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70 % (relative)
- Air changes (per hr): At least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (0600 to 1800) and twelve hours darkness.

IN-LIFE DATES: From: 31 October 2012 To: 21 November 2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: moistened with distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: The back and flanks clipped free of hair.
- % 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 was wiped with cotton wool moistened with distilled water.
- Time after start of exposure: After the 24 hour exposure period, following the removal of the semi-occlusive dressing.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight.

VEHICLE
- Amount(s) applied: The test material was moistened with distilled water prior to application.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
not required
Details on study design:
- Treatment schedule: In the absence of data suggesting toxicity, one male and one female were initially treated at a dose level of 2000 mg/kg. These animals remained in individual housing following exposure. As no mortalities were noted, a further group of animals (four males and four females) was similarly treated with the test material at a dose level of 2000 mg/kg bodyweight to give a total of five males and five females.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes. At the end of the study the animals were killed by cervical dislocation and subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
- Other examinations performed: After removal of the dressings and subsequently once daily, the test sites were examined for evidence of primary irritation and scored according to the Draize scale:

Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) 4

Oedema Formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Any other skin reactions, if present were also recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality.
Clinical signs:
Dehydration was noted in one male one day after dosing. No other signs of systemic toxicity were noted.
Body weight:
Individual bodyweights and weekly bodyweight changes are given in Table 1.
Animals showed the expected gains in bodyweight over the study period with the exception of one female which showed minimal bodyweight loss during the first week but expected gain in bodyweight during the second week and one female which showed expected gain in bodyweight during the first week but minimal bodyweight loss during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
DERMAL REACTIONS
Off white residual test material was noted at the test site of one male.
Very slight erythema (score of 1) was noted at the test site of one female three to five days after dosing. There were no signs of dermal irritation noted in the remaining animals.

Any other information on results incl. tables

Table 1: Individual Bodyweights and Weekly Bodyweight Changes

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Change (g) During Week

0

7

14

1

2

1-0 Male

3-0 Male

3-1 Male

3-2 Male

3-3 Male

254

301

223

247

222

266

312

231

261

226

301

321

243

285

241

12

11

8

14

4

35

9

12

24

15

2-0 Female

4-0 Female

4-1 Female

4-2 Female

4-3 Female

241

210

210

203

200

219

209

219

209

209

216

214

228

219

222

5

-1

9

6

9

-3

5

9

10

13

Applicant's summary and conclusion

Interpretation of results:
other: not classified according to EU criteria
Conclusions:
The LD50 of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight and as such requires no classification in accordance with EU criteria.
Executive summary:

The acute dermal toxicity potential of the test material was assessed in a limit test conducted in the Wistar strain rat in accordance with the standardised guidelines OECD 402 and EU Method B.3.

Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bodyweight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Clinical signs and bodyweight development were monitored during the 14 day observation period. All animals were subjected to gross necropsy.

There were no deaths and no signs of systemic toxicity, though one male animal was dehydrated one day after dosing. Furthermore, the animals showed the expected gains in bodyweight with the exception of one female which showed minimal bodyweight loss during the first week but expected gain in bodyweight during the second week and one female which showed expected gain in bodyweight during the first week but minimal bodyweight loss during the second week.

The only dermal irritation observed was very slight erythema (score of 1) in one female animal three to 5 days after dosing. No abnormalities were noted at necropsy.

The LD50 of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight and as such requires no classification in accordance with EU criteria.