2,6-dimethyloct-7-en-2-yl acetate

Endpoint summary

Description of key information

Skin sensitisation: not sensitising

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:

21st February - 6th April 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Conducted prior to the GLP guidelines

Qualifier:

according to guideline

Guideline:

other: method described by the Magnusson and Kligman "allergic contact dermatitis in the guinea pigs"

Version / remarks:

"allergic contact dermatitis in the guinea pigs" Ed Ch. C. Thomas Springfield, Illinois, USA (1970)

GLP compliance:

no

Remarks:

Conducted prior to the GLP guidelines

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The in vivo guinea pig maximisation test was already available (performed in 1979) and reliable to evaluate the skin sensitization potential and the classification determination.

Specific details on test material used for the study:

100 ml of the test material, dihydromyrcenyl acetate (DHMA) was received on Januray 31, 1979. It was a clear colourless fragrance material.

Species:

guinea pig

Strain:

other: SPF guinea pigs

Sex:

male

Details on test animals and environmental conditions:

A total of 15 young male albino SPF guinea pigs, weighing from 315 to 538 g were obtained from the Central Institute for the breeding of Laboratory animal TNO, Zeist, The Netherlands. The experiment was preceded by an acclimatization period of 10 days to accustom the animals to the environmental conditions prevailing in our laboratory. The guinea pigs were randomly divided into 2 groups, viz. one control group and one test group comprising 5 and 10 animals respectively. They were kept under conventional conditions and individually housed in suspended stainless steel cages, fitted with wire mesh floors and fronts.
Animla room temperature relatively humidity and lighting were controlled at 23+/-1°C , 50+/-% and 12 hours a day respectively. All guinea pigs were fed stock diet enriched with vitamin C, which was provided ad libitum together with tap water.

Route:

intradermal

Vehicle:

other: Freund's adjuvant and distilled water

Concentration / amount:

2 injections of 0.05 ml Freund's Complete adjuvant
2 injections of 0.05 ml of a 10 per cent DHMA dilution in propylene (PG)
2 injections of 0.05 ml of a 10 per cent DHMA suspension in freund's Adjuvant and PG (1:1)
2 injections of 0.05 ml of a 10 per cent DHMA suspension in Freund's Complete adjuvant and PG (1:1)
A concentration of 10% DHMA was chosen for induction because this concentration induced only moderate irritation reactions in preliminary observations.

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

undiluted DHMA

Day(s)/duration:

48 hours

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

10% of DHMA in vaseline

No. of animals per dose:

10 animals

Details on study design:

Induction via intradermal route: an area of 4 x 6 cm of the shoulder region was shaved with electric clippers. Then at short intervals, the intradermal injections were given in an area of 2 x 4 cm. A total of 6 injections was adminstered in 2 rows of 3.

Induction via topical application: One week after the injections, the same area was shaved again and topically treated with the test susbtance. A patch of 2 x 4 cm Whatman 3 mm filter paper was soaked in undiluted DHMA and then placed on the shaven smin and covered by paraplast which was kept in place by adhesive tape. This in turn was firmly secured by the self sticking bandage and left in place for 48 hours.

Challenge: the animals were challenged at day 14 after the topical induction on the right flank of which an area of 5 x 5 cm was shaven. For this treatment DHMA was mixed in vaseline. A concentration of 10% (w/w) which proved to be non irritating in a preliminary test, was used for the challenge. A small amount of the 10% mixture was applied to the shaved area of each animal and gently massaged in with a glass rod for about 30 seconds. The material applied covred an area of about 2 x 2 cm and was covered by a patch of 2 x 2 cm Whatman 3 mm filter paper and paraplast, kept in place by adhesive tape. At the same time the challenge treament was also applied to 5 controls that had not been treated before. Since nearly all animals lost their bandage the challenge was repeated one week later.

Challenge controls:

5 controls

Positive control substance(s):

not specified

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

only very slight erythema in all guinea pigs after the topcial application in the induction phase of the study

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

10%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

other: Positive control was not included

Hours after challenge:

24

Group:

positive control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

Not applicable

Remarks on result:

other: Positive control was not included

All animals remained in a good health during the experiment and gained weight. The intradermal injections given in the induction phase of the study resulted in the following reactions:

1) Freund's Complete Adjuvant : abscesses

2) 10% DHMA in PG: abscesses

3) 10% DHMA in adjuvant and PG (1:1): abscesses

The undiluted DHMA induced a very slight erythema in all guinea pigs after the topical application in the induction phase of the study. Upon the 1st and 2nd challenge none of the animals reacted positively .

The challenge dose generally provoked no erythema or oedema in any of the tested animals. At the same time, none of the controls reacted positively.

Interpretation of results:

other: Not a skin sensitiser

Remarks:

according to EU CLP (EC No. 1272/2008 and its amendments).

Conclusions:

The substance is not a skin sensitiser in the GPMT test according to OECD TG 406.

Executive summary:

The substance was examined fo possible sensitization potential in guinea pigs by means of the maximisation test according to the method described by the Magnusson and Kligman "allergic contact dermatitis in the guinea pigs". A total of 15 young male albino SPF guinea pigs were used for this test including 5 animals for the control.

The induction was firstly done via intra dermal injection: 2 injections of 0.05 ml Freund's Complete adjuvant 2 injections of 0.05 ml of a 10 per cent test substance dilution in propylene (PG) and 2 injections of 0.05 ml of a 10 per cent test substance suspension in freund's Adjuvant and PG (1:1) and 2 injections of 0.05 ml of a 10 per cent test substance suspension in Freund's Complete adjuvant and PG (1:1).

A concentration of 10% test substance was chosen for induction because this concentration induced only moderate irritation reactions in preliminary observations. Secondly the induction was done via topical route using undiluted test material. All animals were challenged with 10% test substance at day 14 after the topical induction.

All animals remained in a good health during the experiment and gained weight. The intradermal injections given in the induction phase of the study resulted in the following reactions:

1) Freund's Complete Adjuvant : abscesses

2) 10% test substance in PG: abscesses

3) 10% test substance in adjuvant and PG (1:1): abscesses

The undiluted test substance induced a very slight erythema in all guinea pigs after the topical application in the induction phase of the study. Upon the 1st and 2nd challenge none of the animals reacted positively .

The challenge dose generally provoked no erythema or oedema in any of the tested animals. At the same time, none of the controls reacted positively. From these test results it is concluded that under the test conditions of this experiment the substance induced no sensitization.

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:

The substance was examined fo possible sensitization potential in guinea pigs by means of the maximisation test according to the method described by the Magnusson and Kligman "allergic contact dermatitis in the guinea pigs". A total of 15 young male albino SPF guinea pigs were used for this test including 5 animals for the control.

The induction was firstly done via intra dermal injection: 2 injections of 0.05 ml Freund's Complete adjuvant 2 injections of 0.05 ml of a 10 per cent test substance dilution in propylene (PG) and 2 injections of 0.05 ml of a 10 per cent test substance suspension in freund's Adjuvant and PG (1:1) and 2 injections of 0.05 ml of a 10 per cent test substance suspension in Freund's Complete adjuvant and PG (1:1).

A concentration of 10% test substance was chosen for induction because this concentration induced only moderate irritation reactions in preliminary observations. Secondly the induction was done via topical route using undiluted test material. All animals were challenged with 10% test substance at day 14 after the topical induction.

All animals remained in a good health during the experiment and gained weight. The intradermal injections given in the induction phase of the study resulted in the following reactions:

1) Freund's Complete Adjuvant : abscesses

2) 10% test substance in PG: abscesses

3) 10% test substance in adjuvant and PG (1:1): abscesses

The undiluted test substance induced a very slight erythema in all guinea pigs after the topical application in the induction phase of the study. Upon the 1st and 2nd challenge none of the animals reacted positively .

The challenge dose generally provoked no erythema or oedema in any of the tested animals. At the same time, none of the controls reacted positively. From these test results it is concluded that under the test conditions of this experiment the substance induced no sensitization.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Respiratory sensitisation can be assessed using human data such as indicated in R7.3.5.2 of the ECHA guidance (2015) that indicate respiratory reactions e. g. from consumer experience or occupational exposure. In case no such data are available the respiratory sensitisation can be assessed using the integrated evaluation strategy for respiratory sensitisation data in the ECHA guidance (R7A, Fig. 7.3-2, 2015), which says that if the substance is not a skin sensitiser, it is unlikely to be a respiratory sensitiser.

Justification for classification or non-classification

Based on the presented information the substance is not a skin and not a respiratory sensitiser, and therefore classification for skin and respiratory sensitisation is not warranted according to EU CLP (EC No. 1272/2008 and its amendments).