Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-04-06 to 1999-04-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
February 24th 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
January 1993
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

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 adults
- Weight at study initiation: 247-274 g
- Fasting period before study: no
- Housing: Individually, in suspended stainless steel cages, wire bottom
- Diet (e.g. ad libitum): Purina Laboratory Rodent Chow 5001 (pellets), ad libitum
- Water (e.g. ad libitum): Domestic water supply (untreated with additional chlorine or HCl), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-67
- Humidity (%): 53-61
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: moistened with 0.5 mL of tap water.
Details on dermal exposure:
TEST SITE
- Area of exposure: scapular to the pelvic region
- Type of wrap if used: hypoallergenic tape

REMOVAL OF TEST SUBSTANCE
- Washing: rinsed with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: depending on the body weight 0.52-0.55 g (males); 0.49-0.54 g (females)
- Concentration: 2000 mg/kg bw
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation for mortality 0.5, 1, 2, 3, 4, 6 hours after dosing and daily thereafter for 14 days
- Necropsy of survivors performed: yes
- clinical signs: observation were done 0.5, 1, 2, 3, 4, 6 hours after dosing and daily thereafter for 14 days
- body weight: was recorded on the day of dosing and again on days 7, 14
- local irritation: was recorded on days 1, 3, 7, 14
Statistics:
The dermal LD50 value and corresponding 95 % confidence limits for separate and combined sexes (if possible) were calculated using a modified Logit-Linear Regression Program written by Jim Gibbons, Texas Instruments Calculator Products Division.

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:
No deaths were noted.
Clinical signs:
Clinical signs noted during the study included abnormal posture, exaggerated hindlimb flexion, staggered gait, abdominogenital staining, abdominal gripping, no feces, chromodacryorrhea, decreased locomotion, diarrhea and unthriftiness. All but one rat recovered by study day 2; one male displayed signs until study day 8.
Body weight:
All rats gained weight by day 14 of the study.
Gross pathology:
No gross internal lesions were observed in any animal during necropsy.
Other findings:
Local irritation: Irritation noted included erythema of the test sites in all rats on day 1. Desquamation, erythema and eschar were noted in some animals on days 3, 7 and 14.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the findings of this study, a single dermal administration of lithium nitrate did not induce mortality as well as test item related adverse effects. A LD50 of >2000 mg/kg bw was determined.
Executive summary:

Lithium nitrate was topically applied to five Sprague-Dawley rats per sex at a dosage level of 2000 mg/kg bw. The test material was in contact with the skin under an occlusive wrap for 24 hours. Observations for toxicity were conducted 0.5, 1, 2, 3, 4, and 6 hours post-dosing, and daily thereafter for fourteen days. Dermal irritation was recorded on days 1, 3, 7 and 14. Body weights were recorded weekly. Gross necropsies were performed on all animals.

No deaths were noted. Clinical signs noted during the study included abnormal posture, exaggerated hindlimb flexion, staggered gait, abdominogenital staining, abdominal gripping, no feces, chromodacryorrhea, decreased locomotion, diarrhea and unthriftiness. All but one rat recovered by study day 2; one male displayed signs until study day 8. All rats gained weight by day 14 of the study. Irritation noted included erythema of the test sites in all rats on day 1. Desquamation, erythema and eschar were noted in some animals on days 3, 7 and 14. No gross lesions were revealed during necropsy. The LD50 determined was greater than 2000 mg/kg bw in both male and female rats. (FMC, 1999)