1,2-Propanediol, 3-(cyclohexyloxy)-

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:

preliminary study: 9-12 Aug 2010; main study: 18 Aug - 11 Sep 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted in 1992

Deviations:

yes

Remarks:

only 5 animals was used in the treatment groups

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

an in vitro skin sensitization study does not need to be conducted because adequate data from an in vivo skin sensitization study is available.

Species:

guinea pig

Strain:

other: Slc:Hartley, SPF

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Japan SLC, Inc., Japan
- Age at study initiation: 5 weeks
- Weight at study initiation: 340-387 g
- Housing: stainless wire mesh cages, 210W x 350D x 180H (mm). 1 animal per cage during the study.
- Diet: Purina experimental diet for guinea pigs 38065. The diet was placed in feeders and provided ad libitum
- Water: public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum via a polycarbonate bottle (500 mL) in an quarantine room and by an automatic watering system in the animal room
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.3-21.5
- Humidity (%): 46.6-71.8
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

First induction: 12%
Second induction: 100%
Challenge: 25%

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

First induction: 12%
Second induction: 100%
Challenge: 25%

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
Two guinea pigs were injected intradermally with 0.1 mL (midline of the shaved shoulder region) of the test substance at dose levels of 100, 50, 25, 12.5, 6.25 and 3.13% w/v (six sites, three of each on the left and right side of the midline of the shaved shoulder region). In addition, for topical applications, 0.1 mL of test substance concentration (100, 50, 25, 12.5, 6.25 and 3.13% w/v) was applied to two further animals. Animals were wrapped with occlusive dressing for 24 hours. The skin reactions were then evaluated at 24 and 48 hours after intradermal injection and 24 and 48 hours after patch removal according to the evaluation standard of skin reaction by Magnusson and Kligman. The following doses were chosen for the main study based on the results of this preliminary study: The dose level for the first induction was selected as 12% as this is approximate to 12.5% which was tested, and which was the highest concentration that did not produce necrosis at the intradermal injection sites. The dose level for the second induction was selected at 100%, as it was the highest concentration that produced slight to moderate skin reactions at the topical application sites. For the challenge induction, the dose level was selected at 25%, as no any skin reactions at the topical application sites were observed at this concentration.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal ( 3 pairs of 0.1 mL injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: 12% (w/v) test substance in water
Injection 3: 12% (w/v) test substance in FCA

Epicutaneous: 0.2 mL of 100% test substance

- Control group:
Intradermal ( 3 pairs of 0.1 mL injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: water
Injection 3: a 1:1 mixture (v/v) FCA/water
- Site: shoulder region
- Frequency of applications: every 7 days
- Duration: 0-8 days
- Concentrations: 12% interdermal and 100% epicutaneous

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: day 21
- Exposure period: 24 h
- Test and control groups: 0.1 mL of the 25% test substance
- Site: flank
- Concentrations: 25%
- Evaluation (hr after challenge): 24 and 48

Challenge controls:

The control group is actually a challenge control

Positive control substance(s):

yes

Remarks:

1-Chloro-2,4-dinitrobenzene (CDNB)

Positive control results:

The positive control substance (0.1% CDNB in olive oil) induced positive reactions in 5/5 animals (100%) at 24 and 48 hours after challenge patch removal. On the other hand, the sensitisation rates for the olive oil challenge sites were determined to be 0% at 24 and 48 hours after challenge patch removal.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Induction intradermal: 12%; challenge: 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: Induction intradermal: 12%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Induction intradermal: 12%; challenge: 25%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction intradermal: 12%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

Induction intradermal: 0.1%; challenge: 0.1%

No. with + reactions:

5

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: Induction intradermal: 0.1%; challenge: 0.1%. No with. + reactions: 5.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Induction intradermal: 12%; challenge: 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: Induction intradermal: 12%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Induction intradermal: 12%; challenge: 25%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction intradermal: 12%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

Induction intradermal: 0.1%; challenge: 0.1%

No. with + reactions:

5

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: Induction intradermal: 0.1%; challenge: 0.1%. No with. + reactions: 5.0. Total no. in groups: 5.0.

Table 2: Mean skin reaction scores

Test group	Substance for sensitisation		Substance for challenge	Score of skin reaction^a	No. of animals		No. of animals with positive reactions	Sensitisation rate (%)
	1^stconcentration	2^ndconcentration			24 hours^b	48 hours^b
G1 Test substance	SDX-3012 (12%)	SDX-3012 (100%)	SDX-3012 (25%)	0	5	5	0/5	0
				1	0	0
				2	0	0
				3	0	0
				Mean score	0.0	0.0
			Water	0	5	5	0/5	0
				1	0	0
				2	0	0
				3	0	0
				Mean score	0.0	0.0
G2 Control	Water	Water	SDX-3012 (25%)	0	5	5	0/5	0
				1	0	0
				2	0	0
				3	0	0
				Mean score	0.0	0.0
			Water	0	5	5	0/5	0
				1	0	0
				2	0	0
				3	0	0
				Mean score	0.0	0.0
G3 Positive control	CDNB (0.1%)	CDNB (0.1%)	CDNB (0.1%)	0	0	0	5/5	100
				1	0	0
				2	0	0
				3	5	5
				Mean score	0.0	0.0
			Olive oil	0	5	5	0/5	0
				1	0	0
				2	0	0
				3	0	0
				Mean score	0.0	0.0

^aMagnusson & Kligman grading scale

^bObservation after patch removal for challenge

CDNB : 1-Chloro-2,4-dinitrobenzene

No abnormal clinical signs or symptoms were evident in any animals throughout the duration of the study. All animals exhibited normal body weight gains. Mean body weight gains were 133 g, 129 g and 134 g in the test substance, negative control and positive control groups, respectively.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation

 

The skin sensitising potential of the test item was evaluated in a Guinea Pig Maximization Test (GPMT) according OECD TG 406 and in compliance with GLP (Yang, 2012c). 5 male Hartley guinea pigs per test group were used for this study. Test substance concentrations selected for the main study were based on the results of a preliminary study. During the induction phase the animals were intradermally injected with 12% test item (diluted in water) and then seven days later topically treated with 100% test material. After a latency of 14 days (to allow a potential reaction with the immune system) the animals were challenged with 25% test material on the flank. The grade of skin reactions was compared to those of the 5 male control animals, which were treated with water during the topical induction phase and, during the challenge phase, with the test item, respectively. The sensitisation rate after application of the test item was 0%. Under the test conditions described, the test item showed no sensitising effects. No other signs of clinical toxicity were reported. Based on the results, the test item was considered not sensitising under the conditions of the test.

Migrated from Short description of key information:

Skin sensitising (OECD TG 406/GPMT): not sensitising

Justification for selection of skin sensitisation endpoint:

There is only one study available.

Justification for classification or non-classification

The available data on skin sensitisation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.