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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-10-01 to 1994-04-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Version / remarks:
1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium carbonate
EC Number:
209-062-5
EC Name:
Lithium carbonate
Cas Number:
554-13-2
Molecular formula:
CH2O3.2Li
IUPAC Name:
dilithium carbonate
Details on test material:
- Name of test material (as cited in study report): Lithium carbonate, Pharmaceutical Grade (Typical Wt% = 99.7; Guaranteed Wt% = 99)
- Analytical purity: 99.2 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: Young adult
- Weight at study initiation: male: 261 g ± 4.1 g; female: 234 g ± 7.4 g
- Housing: individually housed in stainless steel suspended rat cages, wire bottom
- Diet (e.g. ad libitum): ad libitum, Purina Rodent Chow 5001 (pellets)
- Water (e.g. ad libitum): ad libitum, fresh tap water
- Acclimation period: The animals were acclimated for a minimum of 5 calendar days prior to study start.


ENVIRONMENTAL CONDITIONS
- Temperature (degree C): 19 - 22.8 degree C
- Humidity (%): 40 % - 69 %
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent/ 12 hours dark

Administration / exposure

Type of coverage:
occlusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure: intact test site
- Type of wrap if used: The gauze was positioned on the intact test site and held place with hypoallergenic tape. The test site was then covered with an elastic bandage which was lined with plastic.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test sites were wiped with clean gauze moistened with methanol, then rinsed with tap water.
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
Doses corresponding to a dosage level of 2000 mg/kg were individually calculated based on the body weight of each animal on the day of dosing.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality and clinical signs (local irritation excluded): 0.5, 1, 2, 3, 4 and 6 hours on the day of dosing and twice daily thereafter for 13 days; on day 14 the animals were observed once description of the local irritation was recorded on days 1, 3, 7 and 14 of the study, body weights: on days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, local irritation, body weight, necropsy

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
All rats remained healthy during the study.
Body weight:
All rats gained weight during the study. Mean body weights are presented at the table below (see "Remarks on results including tables and figures")
Gross pathology:
There were no gross internal lesions observed in any animals at necropsy.

Any other information on results incl. tables

Mean Body Weights ± SD

 

Day 0

Day 7

Day 14

Male

261 ± 4.1

312 ± 3.4

350 ± 5.4

Female

234 ± 7.4

254 ± 7.0

264 ± 7.2

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the LD50 is greater than 2000 mg/kg in male and female rats when topically applied.
Executive summary:

In accordance with column 2 of REACH Regulation 1907/2006/EC Annex VII section 8.5.3 an acute dermal toxicity study does not need to be conducted if the available information indicates that the criteria are met for classification as corrosive. Both substances, lithium hydroxide and lithium hydroxide monohydrate, are found to be corrosive and a dermal acute toxicity study with the substances as such would not generate meaningful values because of local tissue damage due to corrosiveness. Thus, this study is not required. However, in case of non-corrosive solutions no acute dermal toxicity is expected for lithium hydroxide anhydrous and lithium hydroxide monohydrate. Similar to other lithium salts the acute dermal toxicity is expected to be LD50 is > 2000 mg/kg bw as noted for of e.g. lithium carbonate, reflecting the almost negligible skin penetration of inorganic salts. For this reason, instead of studies with lithium hydroxide and lithium hydroxide monohydrate, the dermal acute toxicity study with lithium carbonate is summarised in the following: The toxic effects of lithium carbonate in Sprague-Dawley rats were investigated according to OECD Guideline 402 and EU method B.3 on acute dermal toxicity. Ten Sprague-Dawley rats (5 males and 5 females) were treated with lithium carbonate Pharmaceutical Grade (Typical Wt% = 99.7; Guaranteed Wt% = 99) at a dosage level of 2000 mg/kg. The test material was in contact with the intact skin for 24 hours under an occlusive wrap. Observations for toxicity were conducted at 0.5, 1, 2, 3, 4 and 6 hours on the day of dosing and twice daily thereafter for 13 days; on day 14 they were conducted once. A description of local irritation was recorded on day 1, 3, 7 and 14. Body weights were recorded on days 0, 7 and 14 of the study. A gross necropsy was performed on all animals. There were no deaths. All rats remained healthy and gained weight by day 14 of the study. No irritations was noted on any of the test sites. All animals appeared normal at necropsy. Under the conditions of this study, the LD50 is greater than 2000 mg/kg in male and female rats when topically applied.