Reaction mass of 6-(butan-2-yl)quinolone and 8-(butan-2-yl)quinoline

Endpoint summary

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:

September 11, 1990 - October 5, 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliability 1 is assigned because the study is conducted according to OECD TG 406, in compliance with GLP, without deviations that influence the quality of the results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1981)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

(1984)no

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

other: Himalayan white spotted GP

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at Acclimatization Start: males: 7 weeks; females: 8 weeks
- Weight at Acclimatization Start: males: 332-394 g; females: 367-397 g
- Housing: individually in Makrolon type-3 cages with standard softwood bedding
- Diet: free access to pelleted guinea pig breeding/maintenance diet (Kliba 342)
- Water: free access to tap water
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: September 11, 1990 To: October 5, 1990

Route:

intradermal and epicutaneous

Vehicle:

other: ethanol

Concentration / amount:

- 5% for the intradermal induction
- 30% for the epidermal induction
- 0, 1, 3 and 10% for the challenge

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Concentration / amount:

- 5% for the intradermal induction
- 30% for the epidermal induction
- 0, 1, 3 and 10% for the challenge

No. of animals per dose:

Test animals: 20 (10 males, 10 females)
Control animals: 10 (5 males, 5 females)

Details on study design:

RANGE FINDING TESTS
- Intradermal injections:
Intradermal injections (0.1 mL/site) were made into the clipped flank of one male and one female at concentrations of 5, 3 and 1% of the test substance in ethanol. Twenty-four hours later the reactions were examined for size, erythema and oedema.
As well-defined erythema (grade 2) was observed with 5% in both animals, this concentration was selected as the intradermal induction concentration.

- Epidermal application:
Patches of filter paper (2x2 cm) were saturated with the undiluted test substance and with concentrations of 30, 10 and 3% in ethanol. These were applied to the clipped and shaved flanks of each of 2 males and 2 females and were covered by a strip of aluminum foil and firmly secured by elastic plaster wrapped around the trunk. The patches were removed 24 hours after application and the treatment sites were examined immediately and 24 hours and 48 hours after removal of the patches.
Although at 30% in all animals only very slight erythema (grade 1) was observed immediately after patch removal and in only 1 animal after 24 hours, this concentration was used for the topical induction concentration. As at 100% (only) well-defined erythema (grade 2) was observed in the animals, using a higher concentration than 30% should have been considered/used.
As at 10% only very slight erythema (grade 1) was observed immediately after patch removal, in only 2 animals, which was reversible within 24h, this concentration was used for the highest challenge exposure.

MAIN STUDY
A. INDUCTION EXPOSURE
1) Intradermal injections
- Concentration: 5%
- Site: the dorsal scapular region
Three pairs of intradermal injections (0.1 mL/site):
1) Freund's complete adjuvant (FCA) 50:50 with physiological saline
2) Test substance at 5% in ethanol
3) Test substance at 5% in ethanol in a 50:50 mixture of FCA with ethanol
Control group:
1) Freund's complete adjuvant (FCA) 50:50 with physiological saline
2) ethanol
3) 50:50 mixture of FCA with physiological saline
- Readings: daily
- Results: Erythema and edema was observed from day 2 to 7, in both groups

2) Topical applications one week after the injections:
- Concentration: 30%
- Amount: saturated patch (control animals: ethanol only)
- Area: 8 cm2
- Exposure period: 48 hours (occlusive)
- Readings: immediately after patch removal and 24 and 48 hours after patch removal

B. CHALLENGE EXPOSURE (control and test group)
- Day of challenge: 2 weeks after the epidermal induction application
- Concentrations: 0, 1, 3 and 10%
- Exposure period: 24 hours (occlusive)
- Sites: anterior left flank (10%); middle left flank (3%); posterior left flank (1%) and right flank (ethanol only)
- Amount: saturated patch
- Readings: immediately after patch removal and 24 and 48 hours after patch removal

Positive control substance(s):

yes

Remarks:

(sensitivity check is done twice a year using a formaldehyde solution)

Positive control results:

The results of the latest sensitivity check of april-may 1990 show that the system is responsive (7 of 10 animals reacted positive)

Reading:

1st reading

Hours after challenge:

0

Group:

negative control

Dose level:

10, 3, 1 and 0%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 0.0. Group: negative control. Dose level: 10, 3, 1 and 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

24

Group:

negative control

Dose level:

10, 3, 1 and 0%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10, 3, 1 and 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

other: 3rd reading

Hours after challenge:

48

Group:

negative control

Dose level:

10, 3, 1 and 0%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10, 3, 1 and 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

0

Group:

test chemical

Dose level:

10, 3, 1 and 0%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 0.0. Group: test group. Dose level: 10, 3, 1 and 0%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10, 3, 1 and 0%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10, 3, 1 and 0%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

other: 3rd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10, 3, 1 and 0%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10, 3, 1 and 0%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Preliminary test

- Upon intradermal injection of 5% clear irritating effects were seen and this concentration was used for induction.

- Upon epidermal application of 100% slight irritation was seen up to 48hour. At 30% irritation was seen after patch removal. For the epidermal application during induction 30% was selected for the main study.

Main study

- Upon intradermal induction, erythema and edema from day 2 to 7; necroses were observed from day 8 to 15; encrustations from day 16 to 20 and exfoliations from day 20 to 25

- Upon epidermal induction at 30%: no skin reactions were observed in the control group; in the test group, very slight erythema (grade 1) was observed in 7 animals directly after patch removal, in 5 animals 24 hours after patch removal and in 2 animals 48 hours after patch removal. Well-defined erythema (grade 2) was only observed in one animal directly after removal. Edema (grade 1) was only observed in one animal, directly after patch removal.

- Upon challenge, 10, 3 and 1% no skin effects were seen.

Other effects

- No mortalities occurred

- No systemic symptoms were observed

- The body weight gain of the animals was normal

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guinea pig maximisation test performed in accordance with OECD 406 (1981) and according to GLP principles, no positive reactions were observed.

Executive summary:

The skin sentisation potential of the substance was investigated by performing a guinea pig maximisation test in accordance with OECD 406 (1981) and according to GLP principles. During the preliminary test it was shown that 5% intradermal injection showed a clear irritant response. Upon 100% topical application sligt skin irritation was seen and at 30% slight irritation was seen at patch removal only. Therefore during the induction intradermal application was at 5% and topical application at 30%. Skin irritation was seen during induction. Therefore at the challenge maximally 10% was used to prevent skin irritant effect also because the substance is a skin irritant. In view of the irritant effects at higher concentrations, the water solubility and log Kow the substance is likely to be absorbed through the skin. No skin reactions were observed after the challenge and therefore the substance is not considered to be a sensitiser.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sentisation potential of the substance was investigated by performing a guinea pig maximisation test in accordance with OECD 406 (1981) and according to GLP principles. During the preliminary test it was shown that 5% intradermal injection showed a clear irritant response. Upon 100% topical application sligt skin irritation was seen and at 30% slight irritation was seen at patch removal only. Therefore during the induction intradermal application was at 5% and topical application at 30%. Skin irritation was seen during induction. Therefore at the challenge maximally 10% was used to prevent skin irritant effect also because the substance is a skin irritant. In view of the irritant effects at higher concentrations, the water solubility and log Kow the substance is likely to be absorbed through the skin. No skin reactions were observed after the challenge and therefore the substance is not considered to be a sensitiser.

Migrated from Short description of key information:
Skin sensitisation, OECd TG 406: Negative

Justification for selection of skin sensitisation endpoint:
This study result of this study is reliable and adequate for covering this endpoint

Justification for classification or non-classification

Sec Butyl Quinoline does not need to be classified as a skin sensitiser based on the Maximisation test, in accordance Regulation (EC) No. 1272/2008 and Directive 67/548/EEC.