Registration Dossier

Administrative data

Description of key information

Based on the findings of a guinea pig Buehler test lithium nitrate was not sensitising to the skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-03-24 to 1999-05-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
July 17th 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
January 1997
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
This study was conducted due to non-REACH regulatory requirements. With the existing data from this study not only being acceptable but of good quality (Klimisch Score 1), this study precludes the need for an additional LLNA study. In addition, a supplementary LLNA study would violate the ECHA objectives with regards to animal welfare.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Covance, Denver, PA
- Age at study initiation: young adults
- Weight at study initiation: 300-500 g
- Housing: individually housed in suspended, polycarbonate cages
- Diet (e.g. ad libitum): Purina Guinea Pig Chow 5025, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 70
- Humidity (%): 46-57
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 100 %, 25 %, 25 % (w/v)
Challenge: 25 % (w/v)
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 100 %, 25 %, 25 % (w/v)
Challenge: 25 % (w/v)
No. of animals per dose:
test group: 20 animals
control group: 10 animals
Details on study design:
RANGE FINDING TESTS:
The irritation range finding phase was conducted to determine the highest, non-irritating concentration of test material to be used for challenge, (defined as that concentration in the solvent that induces responses in four naive guinea pigs no more severe than two grades of 0.5); and to determine the highest moderately irritating concentration of the test material to be used for induction (defined as that concentration in the solvent that results in irritation and induces responses in four guinea pigs no higher than a grade of two in any of the four animals tested). The guinea pigs were dosed by the closed patch method using four different concentrations: 100 % moistened with tap water, and 50 %, 25 %, and 10 % in tap water of the test material, each applied at a dose volume of 0.5 mL or g to a Hilltop Chamber™. Four Hilltop Chambers™ were applied to the back of each animal (two on each side) and were held in place with 1 inch Dermicel tape.
Each guinea pig was wrapped with an elastic, plastic-lined bandage for a 6-hour exposure period. After that the chambers and bandages were removed; any residual test material was wiped away with a clean gauze pad moistened with tap water. Twenty-four hours after unwrapping, the test sites were scored via the Buehler Grading Scale.

MAIN STUDY
A. INDUCTION EXPOSURE
On the day prior to the first induction, the guinea pigs were selected for the study and weighed. The hair was shaved over the right shoulder of each designated animal; the hair was reclipped as needed throughout the study. The animals were dosed by the closed patch method weekly for three applications. The initial induction application was administered using the test material undiluted (slightly moistened with tap water to ensure good skin contact with the skin). Since severe skin reactions were noted following the initial induction, subsequent inductions were administered using a 25 % (w/v) concentration of the test material in tap water. Each dose of 0,5 g or 0.5 mL of the undiluted or diluted test material was measured onto a Hilltop Chamber™ and then applied.
A single Hilltop Chamber™ containing the test material was placed on the right shoulder of each animal in the test group and held in place with 1 inch Dermicel tape. Each guinea pig was wrapped with an elastic, plastic-lined bandage for a 6-hour exposure period, after which the animals were unwrapped, the chambers and bandages were removed, and any residual test material was wiped away with a clean gauze pad moistened with tap water. The test site was moved during induction to prevent cumulative irritation.

B. CHALLENGE EXPOSURE
The concentration of the test material chosen for challenge was 25 % (w/v) in tap water. On day 28, the test and control animals were challenged at a virgin skin site on the left shoulder by the closed patch method as previously described. After approximately six hours the animals were unwrapped, the Hilltop Chambers™ and bandages were removed, and any residual material was wiped away with a clean gauze pad moistened with tap water. Skin reactions were recorded 24 hours after unwrapping each induction application, and 24 and 48 hours after unwrapping the challenge application using the Buehler grading scale.
Challenge controls:
During induction the control animals remained untreated. At the challenge the control group was treated the same as the test animals.
Positive control substance(s):
yes
Remarks:
1-Chloro-2,4-dinitrobenzene (DNCB)
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 % diluted in water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25 % diluted in water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 % diluted in water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 % diluted in water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 % diluted in water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 % diluted in water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25 % diluted in water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 % diluted in water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.05 % (w/v) DNCB in 0.5 mL acetone
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
faint to moderate erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.05 % (w/v) DNCB in 0.5 mL acetone. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: faint to moderate erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.05 % (w/v) DNCB in 0.5 mL acetone
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
very faint to faint erythema, usually nonconfluent
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.05 % (w/v) DNCB in 0.5 mL acetone. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: very faint to faint erythema, usually nonconfluent.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the findings in this guinea pig Buehler test lithium nitrate is not sensitising to the skin.
Executive summary:

Lithium nitrate (0.5 g or mL) was applied weekly to ten male Hartley guinea pigs for three weeks. The initial induction application was applied undiluted. Due to excessive irritation noted, subsequent inductions and the challenge application were applied as a 25 % (w/v) dilution in tap water. Fourteen days after the third induction treatment, the animals were challenged at a virgin site with 0.5 mL of the diluted test material. Additionally, ten naive guinea pigs also received 0.5 mL of the diluted material for the challenge application. Skin reactions were recorded 24 hours following each induction, and 24 and 48 hours following challenge. Body weights were recorded at initiation and termination. All animals remained healthy and gained weight during the study. Twenty-four hours following the first induction application using the undiluted material, severe irritation including erythema and focal necrosis of the test sites was noted. The day prior to the second induction application, all guinea pigs had developed eschar on the initial induction test site. Therefore the concentration was reduced to 25 % in tap water for subsequent inductions and challenge. One guinea pig had a score of 1 following the second induction; another had a score of 0.5 following the second and third inductions. No skin effects were noted following challenge. The test material is judged to be non-sensitizing when topically applied to Hartley guinea pigs. (FMC, 1999)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Lithium nitrate (0.5 g or mL) was applied weekly to ten male Hartley guinea pigs for three weeks. The initial induction application was applied undiluted. Due to excessive irritation noted, subsequent inductions and the challenge application were applied as a 25 % (w/v) dilution in tap water. Fourteen days after the third induction treatment, the animals were challenged at a virgin site with 0.5 mL of the diluted test material. Additionally, ten naive guinea pigs also received 0.5 mL of the diluted material for the challenge application. Skin reactions were recorded 24 hours following each induction, and 24 and 48 hours following challenge. Body weights were recorded at initiation and termination. All animals remained healthy and gained weight during the study. Twenty-four hours following the first induction application using the undiluted material, severe irritation including erythema and focal necrosis of the test sites was noted. The day prior to the second induction application, all guinea pigs had developed eschar on the initial induction test site. Therefore the concentration was reduced to 25 % in tap water for subsequent inductions and challenge. One guinea pig had a score of 1 following the second induction; another had a score of 0.5 following the second and third inductions. No skin effects were noted following challenge. The test material is judged to be non-sensitizing when topically applied to Hartley guinea pigs. (FMC, 1999)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin sensitisation, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.