Indium

Endpoint summary

Description of key information

Indium trihydroxide (In(OH)3 was shown to have no sensitisation potential in the guinea pig according to the Magnusson-Kligman method, using a maximisation method with Freund's complete adjuvant

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

see section 13 in IUCLID for read-across justification report

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The metals industry has historical data to indicate that metals can induce false positives/negatives in LLNA studies; this is confirmed from experiences in test labs.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: LAB-ÁLL Bt. Budapest, 1174 Hunyadi u. 7
- Age at study initiation: Young adult, 8 weeks
- Weight at study initiation: 320 – 351 g
- Housing: Animals were housed in macrolon cages, size III., with 2 or 3 animals/cage (42 x 42 x 19 cm)
- Diet ad libitum: PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary
- Water ad libitum: Animals received tap water from municipal supply as for human consumption, containing 50 mg/100 ml ascorbic acid,
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 23 – 40 %
- Air changes (per hr): 15-20 air exchange/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily from 6 a.m. to 6 p.m. (artificial light)

Route:

intradermal

Vehicle:

other: Methylcellulose

Concentration / amount:

0.01 % (w/v) In(OH)3 in 1% methylcellulose

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

other: Methylcellulose

Concentration / amount:

100% (w/v) In(OH)3 in 1% methylcellulose

Day(s)/duration:

24

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: Methylcellulose

Concentration / amount:

100% (w/v) In(OH)3 in 1% methylcellulose

Day(s)/duration:

48h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

test groups: 10
control group: 5

Details on study design:

RANGE FINDING TESTS:
*) For the intra-dermal treatment: the following formulations were applied:
-0.10 mL of the test item in 1 % methylcellulose at the 5, 1, 0.1 and 0.01 % (w/v) concentrations,
-0.10 mL of test item in 5, 1, 0.1 and 0.01 % (w/v) concentrations, formulated in a 1:1 (v/v) mixture of Freund's Adjuvant (FCA) and physiological saline

It was found that 5, 1 and 0.1 % (w/v) concentrations in 1% methylcellulose and 5, 1 and 0.1 % (w/v) formulated with FCA and saline mixture are inapplicable due to the physical nature of the mixtures, therefore the 5, 1 and 0.1 % (w/v) concentrations in 1 % methylcellulose and in FCA and saline mixture were not tested during the preliminary test, since it will not be technically applicable for the main test.

*)For the dermal application: approximately 0.5 mL of the formulated test item in 1 % methylcellulose was applied at concentrations of 100, 75, 50 and 25 % (w/v) onto the clipped and shaved skin of the animals over an area of 4-6 cm2.


MAIN STUDY (cfr any other information on materials and methods)
A. INDUCTION EXPOSURE
a) intra-dermal induction exposure:
b) dermal induction exposure:
B. CHALLENGE EXPOSURE

Positive control substance(s):

not required

Remarks:

The sensitivity and reliability of the experimental procedure is assessed twice a year by use of items which are known to have moderate skin sensitisation properties (eg 2-mercaptobenzothiazole. 2-mercaptobenzothiazole was classified as skin sensitizer.

Positive control results:

The sensitivity and reliability of the experimental procedure is assessed twice a year by use of items which are known to have moderate skin sensitisation properties such as 2-mercaptobenzothiazole.
Challenge with test item 2-Mercaptobenzothiazole resulted in a positive response in test animals sensitised previously. The net response values at the 24 and 48 hours observations represented an incidence rate of 50 % and 50 % and the net score values of 0.70 and 0.50 respectively. In the control animals no visible changes were found either at the 24 and 48 hours examinations or following challenge with the test item. The dermal scores represented discrete (score1) erythema developed on the skin of sensitised guinea pigs.
On the basis of these results , the test item 2-mercaptobenzothiazole was classified as skin sensitizer.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100% (w/v) (In(OH)3 in 1% methylcellulose

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No overt sign of an adverse clinical response to treatment with the test item during the course of the study

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100% (w/v) (In(OH)3 in 1% methylcellulose

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No overt sign of an adverse clinical response to treatment with the test item during the course of the study

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100% (w/v) (In(OH)3 in 1% methylcellulose

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No overt sign of an adverse clinical response to treatment with the test item during the course of the study

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100% (w/v) (In(OH)3 in 1% methylcellulose

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No overt sign of an adverse clinical response to treatment with the test item during the course of the study

Remarks on result:

no indication of skin sensitisation

Group:

positive control

Remarks on result:

not measured/tested

Main Study

A group of 10 animals was treated with the test item during the induction phase of the study. Injections were given intra-dermally with and without FCA (sensitisation phase I) and one week later the test item was applied dermally on the same site (sensitisation phase II). The animals were challenged by dermal exposure two weeks later with the test item at a concentration of 100 % (w/v) in 1 % methylcellulose.

 

Five control guinea pigs were simultaneously exposed to 1 % methylcellulose during the sensitisation phase I (intra-dermal treatment; with and without FCA). During the sensitisation phase II (dermal treatment) the control animals were treated with1 % methylcellulose and they were treated with the test item at a concentration of 100 % (w/v) in1 % methylcellulose only on the challenge day.

Skin Effects after the Challenge Exposure

 

Test group

 

After the challenge with the test item at a concentration of 100 % (w/v) in1 % methylcellulose, no positive response was observed in the treated animals. The mean of the scores was 0.00 according to the 24 and 48-hours results. The right shaved flank area of all animals was treated with a test item concentration of 50 (w/v) % in 1 % methylcelluloseas a safeguard and no reaction was noted.

 

Control group

 

After the challenge with the test item at a concentration of 100 % (w/v) in1 % methylcellulose no visible changes were found at the 24 and 48 hours examinations. The right shaved flank area of control animals was treated with a test item concentration of 50 (w/v) % in 1 % methylcellulose as a safeguard and no reaction was noted.

 

Clinical Observations

 

There were no overt signs of an adverse clinical response to treatment with the test item during the course of the study.

 

Mortality

 

There were no moribund or dead animals during the study.

 

 Body Weight

 

The individual body weights of the guinea pigs were measured at the beginning and at the end of experiment and there were no notable differences between the test animal group and the control group.

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present assay the test item Indium trihydroxide (In(OH)3 (Batch No.: OH-1306) was shown to have no sensitisation potential and classified as a non-sensitizer, according to current EU-regulations.

Executive summary:

A skin sensitisation study was performed in the guinea pig according to the Magnusson-Kligman method, using a maximisation method with Freund's complete adjuvant to evaluate the sensitisation potential of test item Indium trihydroxide (In(OH)₃.

Ten test animals were subjected to sensitisation procedures in a two-stage process, i.e. an intra-dermal treatment and a topical application. The test item was used at a concentration of 0.01 % (w/v) in 1 % methylcellulose for intra-dermal injections and at a concentration of 100 % (w/v) test item suspension in 1 % aqueous methylcellulose for dermal sensitisation treatment.Two weeks after the last induction exposure, a challenge dose (at a concentration of100 % (w/v) test item suspension in 1 % methylcellulose) was administeredon the left flank of animals.The right flank area of animals was treated with 50 % dilution with 1 % methylcellulose of the maximum dermal challenge dose as a safeguard dose.Challenge was performed by dermal application of the test item.

Five control guinea pigs were simultaneously exposed to 1 % methylcellulose during the sensitisation phase I (intra-dermal treatment). During the sensitisation phase II (dermal treatment) thecontrol animals were treated with1 % methylcelluloseand theywere treated with the test itemat a concentration of 100 % (w/v)and 50 % (w/v)in1 % methylcellulose only during the challenge (phase III).

 

Incidence Rate

 

No signs of contact sensitisation were detected in guinea pigs previously exposed to the test item during the experiments.

 

Intensity of Sensitisation Response

 

In the control and treated animals the mean of the scores was 0.00 according to the 24 and 48-hour results.

In conclusion, under the conditions of the present assay the test item Indium trihydroxide (In(OH)₃(Batch No.:OH-1306) was shown to have no sensitisation potential and classified as a non-sensitizer, according to current EU-regulations.

 

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Read across is applied to a skin sensitisation study on Indium trihydroxide (In(OH)3) performed in the guinea pig according to the Magnusson-Kligman method, using a maximisation method with Freund's complete adjuvant to evaluate the sensitisation potential of test item Indium trihydroxide (In(OH)3 (Török-Bathó, CiToxLAB Hungary 2012).

No signs of contact sensitisation were detected in guinea pigs previously exposed to the test item during the experiments.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based upon read across to Indium trihydroxide (In(OH)₃) skin sensitization data and according to Regulation (EC) No 1272/2008, Indium does not require classification as a skin sensitizer.