potassium titanium oxide (K2Ti6O13)

Endpoint summary

Description of key information

The skin sensitisation potential of the test material was investigated in a study conducted under GLP conditions following the guinea pig maximisation test method. The availability of this study fulfils the information requirements of REACH Regulation. In this in vivo study the test material was judged to be 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:

26 July 1999 to 04 September 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

(Annex V of Council Directive 67/548/EEC)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Date of inspection: 23 March 1998 Date of Signature: 21 July 1998)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A suitable, adequate and reliable in vivo Guinea Pig Maximisation Test (GPMT) already exists (conducted in 1999)

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, United Kingdom.
- Age at study initiation: 8 - 12 weeks old.
- Weight at study initiation: 301 - 357 g.
- Housing: Singly or in pairs in solid-floor polypropylene cages, furnished with woodflakes.
- Diet : Guinea Pig FD1 Diet, Special Diets Services Limited, Witham, Essex, United Kingdom, ad libitum.
- Water : Mains water, ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23°C.
- Humidity (%): 30 - 70%.
- Air changes (per hr): Approximately 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness.

Route:

intradermal

Vehicle:

arachis oil

Concentration / amount:

(induction:)
a) Intradermal induction: 10% in arachis oil b) Topical Induction: 50% in arachis oil
(challenge)
a) 50% in arachis oil BP b) 25% in arachis oil BP

Route:

epicutaneous, occlusive

Vehicle:

arachis oil

Concentration / amount:

(induction:)
a) Intradermal induction: 10% in arachis oil b) Topical Induction: 50% in arachis oil
(challenge)
a) 50% in arachis oil BP b) 25% in arachis oil BP

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS: (Sighting test for intradermal induction) Four concentrations of the test material were investigated (1%, 5%, 10% and 25% w/v in arachis oil BP). Three guinea pigs were used. Each animal received four 0.1 ml injections of only one concentration of test material. (The 25% w/v formulation was not suitable for dosing). Observations at 24, 48, 72 hours and 7 days.
(Sighting test for topical induction) Two guinea pigs were treated at 50%, 25%, 10% and 5% w/w in arachis oil BP for 48 hours under occlusive dressings. Observations at 1, 24 and 48 hours.
(Sighting test for topical challenge) Two guinea pigs were treated at 50%, 25%, 10% and 5% w/w in arachis oil BP for 24 hours under occlusive dressings. Observations at 1, 24 and 48 hours.
See results in appendices I to III, as attached.

MAIN STUDY
A. INDUCTION EXPOSURE
- Test groups: 10 animals.
- Control group: 5 animals.
- Site: Each side of the mid-line.
- Frequency of applications: Twice (Days 0 and 7).
- Duration: 48-h (second application).
- Concentrations: 10%.

B. CHALLENGE EXPOSURE
- Day(s) of challenge: Day 21.
- Site: Shorn right flank of each animal (50%), skin site on the left shorn flank (25%).
- Concentrations: See above.
- Evaluation :24-h and 48-h after challenge. Degree of erythema and oedema, and any other reactions.

Challenge controls:

5 negative controls.

Positive control substance(s):

no

Positive control results:

Not performed.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

25 %

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

25 %

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

50% and 25% in acetone:PEG 400 (70:30)

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

None reported

Remarks on result:

positive indication of skin sensitisation

Remarks:

Positive control material: 2-Mercaptobenzothiazole

Maximum concentration not causing irritating effects in preliminary test: 50 %.

Signs of irritation during induction:

Intradermal Induction:

Discrete or patchy to moderate and confluent erythema was noted at the intradermal induction sites of all test group animals at the 24-hour observation and in nine test group animals at the 48 hour observation.

Discrete or patchy erythema was noted at the intradermal induction sites of three control group animals at the 24-hour observation and in two control group animals at the 48-hour observation.

Topical Induction:

Discrete or patchy erythema was noted at the induction sites of these -test group animals at the 1-hour observation. No skin reactions were noted at the induction sites of test group animals at the 24-hour observation.

No signs of erythema or oedema were noted at the treatment sites of control group animals at the 1 and 24-hour observation.

Evidence of sensitisation of each challenge concentration: Number of animals showing evidence of sensitization at each challenge concentration: 0/10 (with 25 and 50% concentrations).

Interpretation of results:

other: not classified

Conclusions:

The test material produced a 0% (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin. The test material does not meet the criteria for classification according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008).

Executive summary:

A study was performed to assess the contact sensitisation potential of the test material in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 96/54/EC (which constitutes Annex V of Council Directive 67/548/EEC). The results may be used as a basis for classification and labelIing under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC).

Ten test and five control animals were used for the main study.

Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

Intradermal Induction: 10% w/v in arachis oil BP

Topical Induction: 50% w/w in arachis oil BP

Topical Challenge: 50% and 25% w/w in arachis oil BP

The test material produced a 0% (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.

The test material does not meet the criteria for classification according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitisation potential of the substance in the Dunkin-Hartley strain guinea-pig following intradermal induction and topical induction/challenge exposure on the shorn flank was tested. The test methodology complies OECD TG 406 (M&K maximisation test). The results showed no positive reaction under the test condition.

The test material was considered not to be a skin sensitiser under the conditions of the test, based on the results of M&K maximisation test. The test material does not meet the criteria for a skin sensitiser according to the EU classification system (Council Directive 67/548/EEC and under Regulation (EC) No 1272/2008 [CLP]).

The skin sensitisation test described above meet the requirements of OECD Test Guideline 406 (M&K maximisation test) and is assigned a reliability score of 1 according to the scoring system of Klimisch et al (Klimisch et al., 1997). This ranking was deemed appropriate because the study was conducted in a GLP certified laboratory and was in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

There is no information available to assess sensitisation potential of the substance in the respiratory tract.

Justification for classification or non-classification

The test material was considered not to be a skin sensitiser under the conditions of the test, based on the results of M&K maximisation test. The test material does not meet the criteria for a skin sensitiser according to the EU classification system (Council Directive 67/548/EEC and under Regulation (EC) No 1272/2008 [CLP]). The data is lacking for an assessment of classification for respiratory sensitisation for the substance.