Reaction mass of 3,7-dimethyloct-7-en-1-yl 3-methylbut-2-enoate and 3,7-dimethyloctyl 3-methyl-2-butenoate and citronellyl 3-methylcrotonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From March 9, 1983 to April 2, 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 406 skin irritation pre-test

Principles of method if other than guideline:

As part of a Magnusson-Kligman guinea pig maximization, shaved clilpped shoulders of male guinea pigs were patched with 25% dilution of the test sbstance in vaseline for 48 hours under occlusion. Sinodor induced slight skin irritation in 5/10 guinea pigs.

In a primary irritation study, Pirbright white guinea pigs weighing 300-500 g were topically treated on the shorn flank daily with 50 % test material olive oil for 5 days. The test solution was rubbed in for 30 seconds at each application. Animals were individually housed and provided feed and water ad libitum. The room temperature was 20 °C with a humidity of 50 % and a dark/light cycle of 12 hours.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Citronellyl 3-methylcrotonate

EC Number:

244-019-4

EC Name:

Citronellyl 3-methylcrotonate

Cas Number:

20770-40-5

Molecular formula:

C15H26O2

IUPAC Name:

3,7-dimethyloct-6-en-1-yl 3-methylbut-2-enoate

Constituent 2

Reference substance name:

3,7-dimethyloctyl 3-methyl-2-butenoate

EC Number:

275-360-7

EC Name:

3,7-dimethyloctyl 3-methyl-2-butenoate

Cas Number:

71383-07-8

Molecular formula:

C15H28O2

IUPAC Name:

3,7-dimethyloctyl 3-methylbut-2-enoate

Constituent 3

Reference substance name:

3,7-dimethyloct-7-en-1-yl 3-methylbut-2-enoate

Cas Number:

74499-48-2

Molecular formula:

C15H26O2

IUPAC Name:

3,7-dimethyloct-7-en-1-yl 3-methylbut-2-enoate

Test material form:

liquid

Specific details on test material used for the study:

A 200ml sample of the test subtsance was received from the sponsor on December 17, 1982. It was a clear colourless liquid, designated: Sinodor X-09648, No. 211234, date 13.12.82.

Test animals

Species:

guinea pig

Strain:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: Male
- Weight at study initiation: 200 - 400 g
Main test is conducted with 15 young male SPF bred albino guinea pigs (body weight 200-400g) obtained from the central intitute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands.
The experiment is preceded by an acclimatization period of at least two days to accustom the animals to the environmen-tal conditions prevailing in our laboratory.
The guinea pigs are kept under conventional conditions and individually housed in suspended stainless steel cages, fitted with wire mesh floors and fronts. The temperature in the animal room is kept at 21 +/- 1 °C, the relative humidity at 40% at least and a 12 h light/dark cycle is maintained.
The guinea pigs are fed pelleted stock diet from Hope Farms (Woerden, The Netherlands). The diet as well as tap water are provided ad libitum throughout the experiment.

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: vaseline

Controls:

yes

Amount / concentration applied:

FOR TEST GROUP:
1. Induction phase:
- Intradermal applications: 10% Sinodor in propylene glycol, 10% in mixture of FCA and propylene glycol (1:1), FCA only
- Topical application: 25% in vaseline

Challenge: 10% in vaseline

FOR CONTROL GROUP:
1. Induction phase:
- Intradermal applications: FCA only, propylene glycol only, FCA+propylene glycol (1:1) only
- Topical application: vaseline only

2. Challenge: 10% in vaseline

Duration of treatment / exposure:

The diluted test solution in propylene glycol and FCA+propylene glycol was applied during 24 hours.
The diluted test solution in vaseline was applied during 48 hours.
The diluted test solution in vaseline during challenge was applied during 24 hours

Observation period:

Maximum 48 hours

Number of animals:

Test group: 10 animals
Control group: 5 animals

Details on study design:

The test was divided into two stages:
a) induction treatment by intradermal injection and topical application
b) challenge treatment by topical application

Induction is effected in a two-stage operation consisting of, firstly, three pairs of intradermal injections made simultane-ously and, secondly, one week later, a closed patch exposure performed over the injection sites. For this purpose an area of c. 24 cm2 of dorsal skin in the shoulder region is clipped free of hair with electric clippers.

The induction by intradermal injection was performed in two rows of each three injection sites in the shoulder region as follows:
Test animals:
- two injections (0.1 ml) of Freund's Complete Adjuvant (FCA)
- two injections (0.1 ml) of a 10% dilution (w/v) of Sinodor in propylene glycol (PG)
- two injections (0.1 ml) of a 10% dilution (w/v) of Sinodor in FCA and PG (1:1)
Control animals:
- two injections (0.1 ml) of Freund's Complete Adjuvant (FCA)
- two injections (0.1 ml) of propylene glycol (PG)
- two injections (0.1 ml) of FCA and PG (1:1)

Skin readings are made 24h after the treatment.

One week after the intradermal injections, the induction by topical application was made in the same shoulder region. The test animals were treated with a 25% dilution (w/w) of Sinodor in vaseline. The controls were similarly treated with vaseline alone.
The test animals are treated as follows: a 2x4cm patch of Whatman No 3 MM filter paper is loaded with the appropriate mixture of the test substance and carrier. The patch is placed over the sites of the intradermal injections and covered with a piece of PVC foil and a piece of Leukopor hypo-allergic paper bandage. This, in turn, is secured with a 7.5cm wide Tensoplast bandage. The dressing is left in place for 48h. The control animals are similarly treated with patches with car-rier only. Skin readings are made after removal of the patches.

The challenge was carried out two weeks after the topical induction in both test and control animals. The right flank of all animals was topically treated with a 10% dilution (w/w) of Sinodor in vaseline.
An area of 5x5 cm on the left flank of each animal is clipped free of hair and closely shaved. Subsequently a Silverpatch is loaded with the appropriate mixture of the test substance and carrier and place in the centre of the shaved area. The patch is covered with Leukopor bandage which is held in place by Tensoplast. The control animals are also treated with the test substance. The patches are left in place for 24 h. Skin readings are made immediately after removal of the patches and 24 and 48h thereafter.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Time point:

48 h

Remarks on result:

probability of weak irritation

Results 2

Irritation parameter:

erythema score

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

As part of a Magnusson-Kligman guinea pig maximization, shaved clilpped shoulders of male guinea pigs were patched with 25% citronellyl-3-methyl-2-butenoate in vaseline for 48 hours under occlusion. Citronellyl-3-methyl-2-butenoate induced slight skin irritation in 5/10 guinea pigs.

Results 3

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

As part of a Magnusson-Kligman guinea pig maximization, shaved clilpped shoulders of male guinea pigs were patched with 25% citronellyl-3-methyl-2-butenoate in vaseline for 48 hours under occlusion. Citronellyl-3-methyl-2-butenoate induced slight skin irritation in 5/10 guinea pigs.

Irritant / corrosive response data:

The topical applications with the 25% dilution of the test substance in vaseline, made in the induction phase, induced erythema in five out of ten animals.
Vaseline alone did not induce skin reactions in any of the control animals.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Conclusions:

As part of a Magnusson-Kligman guinea pig maximization, shaved clilpped shoulders of male guinea pigs were patched with 25% citronellyl-3-methyl-2-butenoate in vaseline for 48 hours under occlusion.
Citronellyl-3-methyl-2-butenoate induced slight skin irritation in 5/10 guinea pigs.
Not sufficient for classification.

Executive summary:

The test substance Sinodor was examined for possible sensitization potential by a maximization test in guinea pigs.

From the reaction to the challenge treatment with a 10% dilution of the test substance in vaseline, it was concluded that the test substance did not induce delayed contact hypersensitivity in guinea pigs under the conditions of the test.