4,7-methanooctahydro-1H-indene-diyldimethyl bis(2-carboxybenzoate)

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:

1991-01-29 to 1991-02-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to outdated OECD Guideline 406.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

not specified

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study performed prior to availability of LLNA methodology.

Species:

guinea pig

Strain:

other: Bor:DHPW

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen/Kreis Paderborn
- Age at study initiation: 5-7 weeks
- Weight at study initiation: mean of 356 g (315-393 g)
- Housing: 5 animals per cage (Makrolon-cages type IV)
- Diet (e.g. ad libitum): Altromin 3020 pellets ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): ca. 50 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

polyethylene glycol

Concentration / amount:

Intradermal induction: 5 % (w/v)
Topical induction: 25 % (w/v)
Challenge: 25 % (w/v)
[25% is the maximum concentration that can be formulated]

Route:

epicutaneous, occlusive

Vehicle:

polyethylene glycol

Concentration / amount:

Intradermal induction: 5 % (w/v)
Topical induction: 25 % (w/v)
Challenge: 25 % (w/v)
[25% is the maximum concentration that can be formulated]

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS:
- Concentrations: 3, 6, 12 and 25 % (w/v)
- Test animals: 4

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: Intradermal -, topical induction 48 h
- Test groups: 1
- Control group: 1
- Site: dorso-cranial, -medial and -caudal
- Frequency of applications: Intradermal once initially, topical induction once after 7 d
- Duration: 7 d
- Concentrations: 5 % (w/v) for interdermal and 25 % (w/v) for topical

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 d after topical intradermal induction
- Exposure period: 24 h
- Test groups: 1
- Control group: 1
- Site: Left flank for test substance application and right flank for negative control
- Concentrations: 25 % (w/v)
- Evaluation (hr after challenge): 48 and 72 h

Challenge controls:

10 negative control animals

Positive control substance(s):

no

Hours after challenge:

48

Group:

test chemical

Dose level:

25 % (w/v)

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: . Hours after challenge: 48.0. Group: test group. Dose level: 25 % (w/v). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Hours after challenge:

72

Group:

test chemical

Dose level:

25 % (w/v)

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: . Hours after challenge: 72.0. Group: test group. Dose level: 25 % (w/v). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Hours after challenge:

48

Group:

negative control

Dose level:

25 % (w/v)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: . Hours after challenge: 48.0. Group: negative control. Dose level: 25 % (w/v). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Hours after challenge:

72

Group:

negative control

Dose level:

25 % (w/v)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: . Hours after challenge: 72.0. Group: negative control. Dose level: 25 % (w/v). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

No symptoms and no mortalities occurred during the treatment. The gain in weight of the test group was equal to the control group. No skin reactions occurred during the experiment.

The clinical findings for the pilot study for the topical induction having applied test formulations of 3, 6, 12 to a maximum of 25 % are given below. The pilot studies of the same design for finding the application concentration for the challenge yielded exactly the same results for animals 41 to 45.

Erythema and edema:

Animal	3 %		6 %		12 %		25 %
	48 h	72 h	48 h	72 h	48 h	72 h	48 h	72 h
2	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0
4	0	0	0	0	0	0	0	0
5	0	0	0	0	0	0	0	0

The clinical findings for the challenge after 48 and 72 h having applied a 25 % (w/v) test formulation are given below.

Erythema and edema:

Animal	Control group
	Test substance patch		Control patch
	48 h	72 h	48 h	72 h
1	0	0	0	0
2	0	0	0	0
3	0	0	0	0
4	0	0	0	0
5	0	0	0	0
6	0	0	0	0
7	0	0	0	0
8	0	0	0	0
9	0	0	0	0
10	0	0	0	0
Test substance group
21	0	0	0	0
22	0	0	0	0
23	0	0	0	0
24	0	0	0	0
25	0	0	0	0
26	0	0	0	0
27	0	0	0	0
28	0	0	0	0
29	0	0	0	0
30	0	0	0	0
31	0	0	0	0
32	0	0	0	0
33	0	0	0	0
34	0	0	0	0
35	0	0	0	0
36	0	0	0	0
37	0	0	0	0
38	0	0	0	0
39	0	0	0	0
40	0	0	0	0

Bodyweights of animals of the control and test substance group on day 0 and 24 are given below.

Control group			Test substance group
Animal	bw [g] on day 0	bw [g] on Day 24	Animal	bw [g] on day 0	bw [g] on Day 24
1	315	481	21	318	467
2	339	482	22	338	580
3	334	523	23	391	495
4	332	489	24	365	535
5	359	501	25	390	489
6	335	461	26	338	488
7	347	491	27	375	545
8	343	483	28	353	497
9	363	518	29	385	533
10	368	535	30	364	556
11	357	529	31	337	465
12	333	483	32	372	514
13	367	503	33	352	485
14	365	516	34	357	471
15	369	517	35	372	534
16	316	498	36	360	550
17	367	533	37	345	490
18	357	547	38	388	579
19	378	565	39	367	539
20	354	529	40	393	549
Mean	350	509	Mean	363	518
S	18	26	S	21	36

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

After challenge with a 25 % formulation of the test item no skin reactions occurred, neither in the test nor in the control group. The test substance is considered not sensitising to the skin.

Executive summary:

In a GLP-compliant dermal sensitisation study according to OECD guideline 406 with TCD-emulsifier (25 % w/v in polyethylene glycol E400), 20 male young adult guinea pigs (strain: Bor:DHPW) were tested using the method of Magnusson and Kligman (GPMT). No mortalities or clinical symptoms were observed. A 25 % solution of the test item (the maximum attainable concentration for formulations) did not cause primary irritation. Therefore, animals were treated with sodium lauryl sulfate (SLS) prior to topical application of the test item to induce skin irritation.

The animals of the test group were exposed intradermally (5 % w/v) to the test substance, followed by a single topical exposure (25 % w/v) after 7 days. The topical challenge (25 % w/v) was conducted 21 days after the initial intradermal induction for 24 h. Observations were made after 48 and 72 h.  None of the exposed animals showed signs of an allergic reaction.

In this study, the test item is not a dermal sensitiser according to Regulation (EC) 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a GLP compliant dermal sensitization study according to OECD guideline 406 with TCD-emulsifier (25 % w/v) in polyethylene glycol E400, 20 male young adult guinea pigs (strain: Bor:DHPW) were tested using the method of Magnusson and Kligman (GPMT). No mortalities or clinical symptoms were observed. A 25 % solution of the test item (the maximum attainable concentration in formulations) did not cause primary irritation. Therefore, animals were treated with sodium lauryl sulfate (SLS) prior to topical application of the test item to induce skin irritation.

The animals of the test group were exposed intradermally (5 % w/v) to the test substance, followed by a single topical exposure (25 % w/v) after 7 days. The topical challenge (25 % w/v) was conducted 21 days after the initial intradermal induction for 24 h. Observations were made after 48 and 72 h. None of the exposed animals showed signs of an allergic reaction.

Migrated from Short description of key information:
Negative guinea pig maximization test (Magnusson and Kligman) under GLP.

Justification for selection of skin sensitisation endpoint:
GLP guideline study

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In a reliable GLP OECD 406 study, the test substance did not show any sensitizing potential. Classification is not warranted.