Registration Dossier

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

Based on the findings in this guinea pig Buehler test, lithium bromide is sensitising to the skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-10-08 to 1997-03-03
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:
December 29th 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Version / remarks:
November 1984
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Study was performed before LLNA method was described as OECD test guideline and before it could be established in the EU-REACH Regulation. 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.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HRP, Inc., Denver, PA
- Age at study initiation: young adults
- Weight at study initiation: 328-417 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:

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 64-72
- Humidity (%): 47-78
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
100% (LiBr solution undiluted), three applications
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Challenge: 100% (LiBr solution undiluted)
Rechallenge: 100% (LiBr solution undiluted)
No. of animals per dose:
Test group: 10 animals
naive test group: 20 animals (10 animals for challenge, 10 animals for rechallenge)
Details on study design:
RANGE FINDING TESTS:
On the day prior to the beginning of this phase, four guinea pigs were selected. Hair was shaved from the animals' backs. On the following day, the guinea pigs were dosed by the closed patch method. Four different concentrations (undiluted and 50 %, 25 % and 10 % in tap water) of test material were tested; each concentration was placed onto a Hilltop Chamber™. The 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. At the end of the 6-hour exposure period, 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. Approximately 24 hours after unwrapping, the test sites were scored via the Buehler Grading Scale.

MAIN STUDY
A. INDUCTION EXPOSURE
On the day prior to the beginning of the induction phase, the guinea pigs were selected for the study and weighed. The hair was shaved over the right shoulder of each animal designated for induction. The hair was clipped as needed throughout the study.
On day 0, a dose of lithium bromide solution was applied to a Hilltop Chamber™ with a syringe (0.50 mL). Each 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 animal was wrapped with an elastic, plastic-lined bandage. This application was followed by two additional applications, one each on days 7 and 14. The test site was moved during induction to prevent cumulative irritation.
The test material was left in contact with the skin of the right shoulder for approximately six hours. At the end of the exposure period the animals were unwrapped, the Hilltop Chambers™ and bandages were removed, and any residual test material was wiped away with clean gauze moistened with tap water.

B. CHALLENGE EXPOSURE
On day 28, the animals were challenged at a virgin skin site (left shoulder); the animals were dosed by the closed patch method as previously described. Animals in the test and the naive test groups received 0.50 mL of the undiluted test material on the left shoulder.
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.

C. RECHALLENGE EXPOSURE
A re-challenge was performed on the test group one week later on day 35. Ten new animals were used to serve as the naive test group. All animals were dosed on a virgin test site on the right flank. The concentration chosen for re-challenge was the highest non-irritating level (undiluted) of the test material. The animals were dosed in the same manner as the challenge application, except the patches were placed on the right flank of each animal.
Challenge controls:
Naive controls of the challenge and rechallenge exposure remained untreated during the induction phase. During challenge and rechallenge they were treated the same as the test group.
Positive control substance(s):
yes
Remarks:
1-Chloro-2,4-dinitrobenzene (DNCB)
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% (LiBr undiluted)
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
very faint nonconfluent erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100% (LiBr undiluted). No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: very faint nonconfluent erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% (LiBr undiluted)
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
very faint non confluent erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100% (LiBr undiluted). No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: very faint non confluent erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% (LiBr undiluted)
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
strong erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% (LiBr undiluted). No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: strong erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% (LiBr undiluted)
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
3 animals with very faint erythema, 2 animals with strong erythema
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% (LiBr undiluted). No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: 3 animals with very faint erythema, 2 animals with strong erythema.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
100% (LiBr undiluted)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 100% (LiBr undiluted). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
100% (LiBr undiluted)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 100% (LiBr undiluted). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
100% (LiBr undiluted)
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
1 animal with moderate erythema, 3 animals with strong erythema
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 100% (LiBr undiluted). No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: 1 animal with moderate erythema, 3 animals with strong erythema.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
100% (LiBr undiluted in water)
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
1 animal with moderate erythema, 3 animals with strong erythema
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 100% (LiBr undiluted in water). No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: 1 animal with moderate erythema, 3 animals with strong erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.4% (w/v) DNCB in 80% ethanol
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
9 animals with moderate erythema, 1 animal with strong erythema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.4% (w/v) DNCB in 80% ethanol. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: 9 animals with moderate erythema, 1 animal with strong erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.4 % (w/v) DNCB in 80% ethanol
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
6 animals with moderate erythema, 4 animals with strong erythema
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.4 % (w/v) DNCB in 80% ethanol. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: 6 animals with moderate erythema, 4 animals with strong erythema.
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Based on the findings in this guinea pig Buehler test lithium bromide is sensitising to the skin.
Executive summary:

A guinea pig Buehler test was performed with lithium bromide according to OECD guideline 406 and EU method B.6. Lithium bromide solution (0.50 mL) was applied to the right shoulder of each of ten male Hartley guinea pigs for a six hour exposure period at weekly intervals for three weeks. Fourteen days after the third induction treatment, the animals were challenged at a virgin skin site. The concentration of the test material chosen for challenge of the test group was the undiluted test material, which was the highest non-irritating concentration as determined during the range-finding phase of this study. An additional ten male naive animals (naive test group) also received 0.50 mL of the undiluted test material for the challenge application. Observations for skin reactions were recorded approximately 24 hours after unwrapping each induction application and approximately 24 and 48 hours following unwrapping of the challenge application. On day 35 a re-challenge was performed using the original test animals and a new naive test group; the animals received the undiluted test material. Observations for skin reactions were recorded approximately 24 and 48 hours following unwrapping of the re-challenge application. Body weights were recorded at initiation and termination.

All animals remained healthy and gained weight during the study. Three animals in the test group displayed very faint to faint erythema following the first induction; irritation worsened with subsequent inductions. Following challenge of the test group, very faint erythema was noted in 3 males and strong erythema and necrosis were noted in two males. The only irritation noted among naive test animals during challenge was very faint erythema in three guinea pigs. During re-challenge one male in the test group had moderate erythema and 3 males in the test group had strong erythema and necrosis. No irritation was noted among the naive test animals during re-challenge.

Under the conditions of this study, the test material was judged to be sensitising when topically applied to Hartley guinea pigs. (FMC, 1997)

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A guinea pig Buehler test was performed with lithium bromide according to OECD guideline 406 and EU method B.6. Lithium bromide solution (0.50 mL) was applied to the right shoulder of each of ten male Hartley guinea pigs for a six hour exposure period at weekly intervals for three weeks. Fourteen days after the third induction treatment, the animals were challenged at a virgin skin site. The concentration of the test material chosen for challenge of the test group was the undiluted test material, which was the highest non-irritating concentration as determined during the range-finding phase of this study. An additional group of ten male animals (naive test group) also received 0.50 mL of the undiluted test material for the challenge application. Observations for skin reactions were recorded approximately 24 hours after unwrapping each induction application and approximately 24 and 48 hours following unwrapping of the challenge application. On day 35 a re-challenge was performed using the original test animals and a new naive test group; the animals received the undiluted test material. Observations for skin reactions were recorded approximately 24 and 48 hours following unwrapping of the re-challenge application. Body weights were recorded at initiation and termination.

All animals remained healthy and gained weight during the study. Three animals in the test group displayed very faint to faint erythema following the first induction; irritation worsened with subsequent inductions. Following challenge of the test group, very faint erythema was noted in 3 males and strong erythema and necrosis were noted in two males. The only irritation noted among naive test animals during challenge was very faint erythema in three guinea pigs. During re-challenge one male in the test group had moderate erythema and 3 males in the test group had strong erythema and necrosis. No irritation was noted among the naive test animals during re-challenge.

Under the conditions of this study, the test material is judged to be sensitising when topically applied to Hartley guinea pigs. (FMC, 1997)


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 has to be classified and labelled as skin sens. cat. 1, H317 (May cause an allergic skin reaction) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.