Ceramic materials and wares, chemicals

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

2009-07-07 - 2009-07-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Relative humidity in the animal room was between 45-100% for few hours.

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Spinel (Mg(AlO2)2)

EC Number:

215-105-9

EC Name:

Spinel (Mg(AlO2)2)

Cas Number:

1302-67-6

IUPAC Name:

1302-67-6

Constituent 2

Reference substance name:

magnesium dialuminium oxide

IUPAC Name:

magnesium dialuminium oxide

Details on test material:

Batch no.: SP-AR78-20MY, batch 0825193518
Purity: > 99%
Expiration date: unlimited stability

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

10, 25, 50 %

No. of animals per dose:

4

Positive control substance(s):

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

Results and discussion

Positive control results:

Experiment performed in June 2009.
Positive control substance: alpha-Hexylcinnamaldehyde
Vehicle: acetone:olive oil (4+1)
Test item concentration % (w/v) Group Measurement DPM DPM-BG a) number of lymph nodes DPM per lymph node b) S.I.
--- BG I 23 --- --- --- ---
--- BG II 19 --- --- --- ---
0 1 5842 5821 8 727.6
5 2 10450 10429 8 1303.6 1.79
10 3 12168 12147 8 1518.4 2.09
25 4 39834 39813 8 4976.6 6.84

BG = Background (1 ml 5% trichloroacetic acid) in duplicate
1 = Control Group
2-4 = Test Group
S.I. = Stimulation Index
a) = The mean value was taken from the figures BG I and BG II
b) = Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured value by the number of lymph nodes pooled

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: 10 %: 1.17 25 %: 1.88 50%: 1.42

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

Test item concentration % (w/w) Group Measurement DPM DPM-BGa) number of lymph nodes DPM per lymph nodeb) S.I. --- BG I 29 --- --- --- --- --- BG II 26 --- --- --- --- --- 1 4932 4905 8 613.1 10 2 5770 5743 8 717.8 1.17 25 3 9240 9213 8 1151.6 1.88 50 4 6996 6969 8 871.1 1.42 BG = Background (1 ml 5% trichloroacetic acid) in duplicate 1 = Control Group 2-4 = Test Group S.I. = Stimulation Index a) = The mean value was taken from the figures BG I and BG II b) = Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured value by the number of lymph nodes pooled The EC3 value could not be calculated, since all S.I.´s are below 3.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Pleonaste is not a skin sensitiser.

Executive summary:

Justification for read-across:

Spinel type minerals all have a spinel crystal structure, no water solubility and high melting points. Their behaviour in water and biological systems is dominated by their insolubility and missing bioavailability. They constitute in general practically inert materials also with regard to their content of metal ions. Thus, they to not contribute to any ecological hazards. They are also not bioavailable in vivo, which was confirmed by solubility tests in surfactant and stomach/small intestine fluids. The Spinel type minerals are not skin irritating and not eye irritating in the conducted in vitro tests. In addition, there is no sensitizing concern for the Pleonaste metal constituents Fe. Al and Mg.

Physico-chemical properties of Spinel and Pleonaste:

	Spinel	Pleonaste
density (g/cm3)	3.55	3.82
melting-point (degree C)	2,135	> 1,650
water-solubility	insoluble	insoluble
bioavailability in the digestive tract	not bioavailable	not bioavailable
bioavailability in the lung	not bioavailable	not bioavailable
crystal structure	spinel lattice	spinel lattice

Conclusions:

In order to study a possible contact allergenic potential of Spinel, three groups each of four female mice were treated daily with the test item at concentrations of 10, 25, and 50% (w/w) in dimethylformamide 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 (dimethylformamide) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled 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 of³H-methyl thymidine measured in ab-scintillation counter.

All treated animals survived the scheduled study period and no signs of toxicity were observed.

A test item is regarded as a sensitiser in the LLNA if the exposure to one or more test concentration resulted in 3-fold or greater increase in incorporation of³HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.). The estimated concentration of test item required to produce a S.I. of 3 is referred to as the EC3 value.

In this study Stimulation Indices of 1.17, 1.88, and 1.42 were determined with the test item at concentrations of 10, 25, and 50% in dimethylformamide. The EC3 value could not be calculated, since none of the tested concentrations induced an S.I. greater than 3.

Applying read-across it can be concluded that Pleonaste is not skin-sensitising.