Gadolinium oxide sulfide (Gd2O2S), praseodymium-doped

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 March 2003 - 22 April 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Gadoliniumsulfite trihydrate

EC Number:

456-900-2

EC Name:

Gadoliniumsulfite trihydrate

Cas Number:

51285-81-5

Molecular formula:

Gd2(SO3)3*3H2O

IUPAC Name:

Gadoliniumsulfite trihydrate

Test material form:

solid: particulate/powder

Details on test material:

Off white, crystalline powder
Batch number FSG 3896 or 02-FW-095

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/CaOiaHsd

Sex:

female

Details on test animals and environmental conditions:

Standard Labaratory Conditions. Air-conditioned with target ranges for room temperature 22 ± 3 °C, relative humidity 30 - 70 % and 10 - 15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. There was a 12 hour fluorescent light / 12 hour dark cycle with at least 8 hours music during the light period. In groups of four in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz). Pelleted standard Kliba 3433, batch no. 90/02 mouse maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum. Results of analyses for contaminants are archived at RCC. Community tap water from ltingen, available ad libitum. Results of representative bacteriological, chemical and contaminant analyses are archived at RCC.

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

1 %, 2.5 %, 5 %
ln a non-GLP conform pre-test in two mice, test item concentrations of 1 %, 5 %, 10 % and 25 % (w/v) were tested on one ear each. No Irritation effects were observed at the dosing sites applied at concentrations of 1 % or 5 % (w/v). At the observation of 24 hours after the topical application, a slight swelling was noted at the local sites dosed at 10 % and 25 %. 5 % (w/v) was the highest technically achievable concentration whilst avoiding systemic toxicity and excessive local irritation.

No. of animals per dose:

4

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

1 % test group

Results 2

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

2.5 % test group

Results 3

Key result

Parameter:

SI

Value:

1.7

Test group / Remarks:

5.0 % test group

Any other information on results incl. tables

No test item-related clinical signs were observed in any animals of the control group or Group 2 (1 %). On the second application day, a slight tomoderate swelling was observed at both dosing sites in all mice of Group 3 (2.5 %) and Group 4 (5 %), persisting for four to five days. The body weight of the animals, recorded at the start of acclimatization period and prior to necropsy, was within the range commonly recorded for animals of this strain and age.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In this study STIMULATION INDICES of 1.0, 1.0 and 1.7 were determined with the test item at concentrations of 1 %, 2.5 % and 5 % (w/v) in acetone:olive oil, 4:1 (v/v). A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the STIMULATION INDEX (S.I.). The test item Gadolinium sulfite trihydrate was found to be a non-sensitizer when tested at concentrations of up to 5 % (w/v). Gadolinium sulfite trihydrate showed a local Irritation when tested at concentrations of 2.5 % and 5 % (w/v).

Executive summary:

In order to study a possible contact allergenic potential of Gadolinium sulfite trihydrate, three groups each of four female mice were treated daily with the test item at concentrations of 1 %, 2.5 % and 5 % (w/v) in acetone:olive oil, 4:1 (v/v) by topical application to the dorsum of each ear lobe (left and right) for three consecutive days. A control group of four mice was treated with the vehicle (acetone:olive oil, 4:1 (v/v)) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labellad thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a beta-scintillation counter.No test item-related clinical signs were observed in any animals of the control group or Group 2 (1 %). On the second application day, a slight to moderate swelling was observed at both dosing sites in all mice of Group 3 (2.5 %) and Group 4 (5 %), persisting for four to five days. All treated animals survived the scheduled study period. In this study STIMULATION INDICES of 1.0, 1.0 and 1.7 were determined with the test item at concentrations of 1 %, 2.5 % and 5 % (w/v) in acetone:olive oil, 4:1 (v/v). A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the STIMULATION INDEX (S.I.). The test item Gadolinium sulfite trihydrate was found to be a non-sensitizer when tested at concentrations of up to 5 % (w/v). Gadolinium sulfite trihydrate showed a local Irritation when tested at concentrations of 2.5 % and 5 % (w/v).