4-trans-Pentyl-[1,1-bicyclohexyl]-4-on

Endpoint summary

Description of key information

The test item showed no skin sensitising effects on the tested animals. Therefore, it is not a skin sensitiser (reference 7.4.1-1).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04-06-1991 to 06-08-1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: MAGNUSSON and KLIGMAN (1969)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The guinea pig test method described in OECD TG 406 provide suitable information for hazard identification.

Species:

guinea pig

Strain:

other: Iva: PDH

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Females: nulliparous and non-pregnant: yes
- Age at study initiation: 6 weeks
- Weight at study initiation: 300 - 365 g, mean: 323 g
- Housing: Makrolon cages type IV, individual cages
- Diet: ad libitum, Altrorain Standard Diet TPF (R) 3012
- Water: ad libitum, tap water from Makrolon drinking bottles
- Acclimation period: 7 days before the start of the treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 - 31
- Humidity (%): 42 - 60
- Photoperiod (hrs dark / hrs light): 12 / 12

Route:

intradermal

Vehicle:

other: with and without Freund's complete adjuvant (FCA)

Concentration / amount:

0.05 %

Day(s)/duration:

day 0 / single application

Adequacy of induction:

other: slightly irritant

Route:

epicutaneous, occlusive

Vehicle:

other: Liquid paraffin

Concentration / amount:

10 %

Day(s)/duration:

day 8 / 48 hours

Adequacy of induction:

other: slightly irritant

Route:

epicutaneous, occlusive

Vehicle:

other: Liquid paraffin

Concentration / amount:

1 %

Day(s)/duration:

day 22 / 24 hours

Adequacy of challenge:

other: not irritant

No. of animals per dose:

2 groups of 10 males and 10 females

Details on study design:

Test Item Preparation: The test material was diluted with liquid paraffin or FCA preparation (Freund's complete adjuvant) prior to application.

RANGE FINDING TESTS:
A pretest with single intracutaneous and epicutaneous administration of the vehicle and of the test item preparations was performed, to determine concentrations suitable for the main study.
In the pretest the following concentrations were used:
Vehicle: undiluted
Test item: i.e.: 0.05, 0.5, and 2.5 g ad 100 mL; e.c: 1.0 and 10.0 g ad 100 mL

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 induction stages - 6 injections per induction stage
- Test groups: Group 2: treated with test material preparations
- Control group: Group 1: treated with liquid paraffin (vehicle)
- Site: shoulder region
- Duration: 2 weeks
- Concentrations: Vehicle: Liquid paraffin (undiluted)
Test material: intradermal induction: 0.05 % (slightly irritant), topical induction: 10.00 % (slightly irritant)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Exposure period: 24 hours
- Test groups: patch soaked with 1 mL test material on the left shaven flank
- Control group: patch soaked with vehicle on the right shaven flank
- Site: left flank of the animal
- Concentrations: topical challenge: 1.00 % (not irritant)
- Evaluation (hr after challenge): 24 and 48

CLINICAL INVESTIGATIONS:
During the induction phase the guinea-pigs were examined daily for local skin reactions, and the results were documented. The challenge sites were investigated for reactions 24 hours after removal of the patches. Further inspections followed 48 hours after challenge, to detect weak or slowly developing reactions, also.

BODY WEIGHT: The body weight of the guinea-pigs was determined prior to the start of the study, and then once weekly.

Challenge controls:

righ flank of the animal

Positive control substance(s):

yes

Remarks:

1-chloro-2,4-dinitrobenzene (DNCB)

Positive control results:

In a separate study, the positiv control DNCB was tested. 100 % positive skin reaction to 0.01 % formulation was determined after 24 and 48 hour readings. The guinea pig strain has been shown to be sensitive and suitible for further testing.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

1 % formulation

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Clinical behaviour of the guinea pigs was normal during the study period.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

1 % formulation

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Clinical behaviour of the guinea pigs was normal during the study period.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1 % formulation

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Clinical behaviour of the guinea pigs was normal during the study period.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1 % formulation

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Clinical behaviour of the guinea pigs was normal during the study period.

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.01 % formulation

No. with + reactions:

20

Total no. in group:

20

Clinical observations:

Clinical behaviour of the guinea pigs was normal during the study period.

Remarks on result:

positive indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.01 % formulation

No. with + reactions:

20

Total no. in group:

20

Clinical observations:

Clinical behaviour of the guinea pigs was normal during the study period.

Remarks on result:

positive indication of skin sensitisation

Findings in the induction phase

After intradermal injection the usual irritation seen after treatment with Freund's complete adjuvant was observed. The injection sites were swollen and red. Later necrosis and scabs were observed. Similar findings were seen with liquid paraffin. After removal of the patches scabs and scales were observed at the topical application sites.

Findings after challenge

Group 1 was used as negative control. Challenge on the right flank was performed with the vehicle. On the left flank a single application of a 1.0 % test item formulation was performed to exclude primary irritation. No irritation was observed.

Group 2, the test material group, was exposed to undiluted liquid paraffin on the right and to 1.0 % test item on the left flank. No abnormalities were detected with liquid paraffin and with the test item.

Table 1: Positive reactions (percent) after challenge (sensitization rate)

Group	Test material	Time points
		24 h	48 h	Total
1	Liquid paraffin	0/20 (0 %)	0/20 (0 %)	0/40 (0 %)
2	Test item preparation	0/20 (0 %)	0/20 (0 %)	0/40 (0 %)

Table 2: Challenge reactions at the quinea pig flanks - test item

Group 1: liquid paraffin - undiluted	Males no.
	Hours	381	382	383	384	385	386	387	388	389	390
	24	0	0	0	0	0	0	0	0	0	0
	48	0	0	0	0	0	0	0	0	0	0
	Females no.
	Hours	391	392	393	394	395	396	397	398	399	400
	24	0	0	0	0	0	0	0	0	0	0
	48	0	0	0	0	0	0	0	0	0	0
Group 2: 1 g test item in 100 mL paraffin	Males no.
	Hours	361	362	363	364	365	366	367	368	369	370
	24	0	0	0	0	0	0	0	0	0	0
	48	0	0	0	0	0	0	0	0	0	0
	Females no.
	Hours	371	372	373	374	375	376	377	378	379	380
	24	0	0	0	0	0	0	0	0	0	0
	48	0	0	0	0	0	0	0	0	0	0

Positive reaction after challenge:

24 hours: 0 %

48 hours: 0 %

Total: 0 %

Table 3: Challenge reactions at the quinea pig flanks – positive control

Group 1: liquid paraffin - undiluted	Males no.
	Hours	321	322	323	324	325	326	327	328	329	330
	24	0	0	0	0	0	0	0	0	0	0
	48	0	0	0	0	0	0	0	0	0	0
	Females no.
	Hours	331	332	333	334	335	336	337	338	339	340
	24	0	0	0	0	0	0	0	0	0	0
	48	0	0	0	0	0	0	0	0	0	0
Group 2: 0.01 % positive control formulation	Males no.
	Hours	301	302	303	304	305	306	307	308	309	310
	24	+	+	+	+	+	+	+	+	+	+
	48	+	+	+	+	+	+	+	+	+	+
	Females no.
	Hours	311	312	313	314	315	316	317	318	319	320
	24	+	+	+	+	+	+	+	+	+	+
	48	+	+	+	+	+	+	+	+	+	+

Positive reaction after challenge:

24 hours: 100 %

48 hours: 100 %

Total: 100 %

Clinical findings and mortality

The clinical behavior of the guinea-pigs was normal during the study period. All animals survived the study period.

Body weight

The body weight development did not differ from that of the animals of the vehicle group. All animals survived the study period.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item showed no skin sensitising effects on the tested animals. Therefore, it is not a skin sensitiser.

Executive summary:

The test item was tested for skin sensitising properties in the guinea-pig maximization test according to MAGNUSSON and KLIGMAN (1969) and OECD 406. 10 males and 10 females per group were investigated. Group 1 was treated with undiluted liquid paraffin (vehicle) and group 2 with the test item (test material preparations). Induction included intradermal injection of the test material (0.05 %, with and without Freund's complete adjuvant) on day 1, and topical application of the test material (10 %) on day 8 of the study. Challenge by topical application of a 1 % test material preparation was performed three weeks after intradermal induction. Treatment with the vehicle did not lead to positive reactions at the 24 h and 48 h readings after challenge. Treatment with the test item as 1 % formulation was without effects at the 24 h and 48 h readings. Under the experimental conditions given, the test item did not show sensitizing properties. According to the grading scheme of MAGNUSSON and KLIGMAN compounds with a sensitization rate of 0 - 8 % have to be classified as weak sensitizers. According to OECD 406 criteria the test item is not considered to possess skin sensitising properties.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

OECD 406

The test item was tested for skin sensitising properties in the guinea-pig maximization test according to MAGNUSSON and KLIGMAN (1969) and OECD 406. 10 males and 10 females per group were investigated. Group 1 was treated with undiluted liquid paraffin (vehicle) and group 2 with the test item (test material preparations). Induction included intradermal injection of the test material (0.05 %, with and without Freund's complete adjuvant) on day 1, and topical application of the test material (10 %) on day 8 of the study. Challenge by topical application of a 1 % test material preparation was performed three weeks after intradermal induction. Treatment with the vehicle did not lead to positive reactions at the 24 h and 48 h readings after challenge. Treatment with the test item as 1 % formulation was without effects at the 24 h and 48 h readings. Under the experimental conditions given, the test item did not show sensitizing properties. According to the grading scheme of MAGNUSSON and KLIGMAN compounds with a sensitization rate of 0 - 8 % have to be classified as weak sensitizers. According to OECD 406 criteria the test item is not considered to possess skin sensitising properties (reference 7.4.1-1).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified as a skin sensitiser under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.