Reaction mass of decyl acrylate and octyl acrylate

Endpoint summary

Description of key information

An old sensitisation test on available on the reaction mass of octyl and decyl acrylate: a mouse ear swilling test showing positive reaction and allowing to conclude that the registered substance is a skin sensitizer. However this test cannot allow to determine a sub-category of classification according to the Regulation EC n°1272/2008.

That's why a second study, performed on one of major constituents of the registered substance is used for assessment. Octyl acrylate showed positive reaction in the maximization method of Magnusson and Kligman (GPMT) leading to the sub-category 1B.

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:

weight of evidence

Study period:

April - August 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

An old and reliable study is available on an analogue substance of the registered substance before the registration data ; so no new study with animal will be performed.

Specific details on test material used for the study:

no

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River France, 76410 Saint-Aubin-les-Elbeuf, France
-Females were nulliparous and non-pregnant.
- Age at study initiation: 3 months old
- Weight at study initiation: 341 +/-10 g (males), 344+/-17 (females)
- Housing:individually in polycarbonate cages
- Diet (e.g. ad libitum): free access to "106 pelleted diet"
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Humidity (%):30-70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal

Vehicle:

other: corn oil

Concentration / amount:

10%

Day(s)/duration:

on Day 1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

on Day 8

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

on Day 22

No. of animals per dose:

range-finding study : 2 males and 2 females
Main study : 15 males and 15 females

Details on study design:

RANGE FINDING TESTS:
By intradermal route: 24 hours before treatment, the dorsal region of the animal was clipped; intradermal administrations of the test substance formulation at different concentrations were performed in the intersacpular region; cutaneous reactions were evaluated appox. 24,48 and 6 days after injection.
By cutaneous route: 24 hours before teatment, both flank regions of the animals were clipped; a volume of 0.5 ml of the undiluted test substance of test substance formation at the chosen concentrations was placed on a dry gauze pad (approx. 4 cm²) which was then applied to the skin and held in place by an occlusive dressing for 24 hours; cutaneous reactions were evaluated approx. 24 and 48 hours after removal of the dressings.

MAIN STUDY
For all animals and before each treatment, the application sites were clipped on days 1 and 7 (intersacpular region 4 cm x 2 cm), clipped and shaved on day 21 (each flank 2 cm x 2 cm) and clipped on day 25 (each flank 2 cm x 2 cm).

A. INDUCTION EXPOSURE
- No. of exposures: 2 (day 1 : intradermal route ; day 8 : topical route)
- Control group: corn oil
- Site: intersacpular region
- Concentrations: intradermal route = 10% in corn oil ; topical route = 100 % (undiluted)
-Intradermal route : 3 injections per animal of 0.1 ml were made into each side of the interscapular region:
First injection (anterior site): FCA diluted at 50% (v/v) with 0.9% NaCL fro treated and control groups
Second injection (middle site): test substance at 10% (w/w) in corn oil for treated group ; vehicucle for control group
Third injection (posterior site): test substance at 10% (w/w) in a mixture FCA/0.9% NoCl 50/50 (v/v) for treated group ; vehicle at 50% (w/w) in a mixture FCA/0.9% NoCl 50/50 (v/v) for control group.
-topical roue: on day 8, 0.5 ml of the undiluted substance for treated group, and 0.5mlm of vehicle for control group. The test substance or the vehicule was placed on a dry gauze pad, which was then applied to the interscapular region. The pad was held in place for 48 hours by means of an adhesive hypoallergenic dressing and an adhesive anallergenic waterproof plaster. on removal of the dressing, no residual test substance was observed.

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (cutaneous)
- Day(s) of challenge: day 22
- Test groups: 0.5 ml of the undiluted test substance
- Control group: 0.5 ml of the vehicle
- Site: posterior right flank (treated), left (control group)
- Evaluation (hr after challenge): 24 and 48h after removal of the dressing
The test substance or the vehicule was placed on a dry gauze pad, which was then applied to the posterior region. The pad was held in place for 24 hours by means of an occlusive anallergenic waterproof plaster. On removal of the dressing, no residual test substance was observed.

Challenge controls:

no

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10% then 100%

No. with + reactions:

18

Total no. in group:

20

Clinical observations:

18 animals showed a grade 2 erythema ; one with grade 1

Key result

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

10% then 100%

No. with + reactions:

17

Total no. in group:

20

Clinical observations:

well defined or moderate erythema were observed : 10 animals with grade 2 and 7 animals with a grade 3

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no erythema with grade 2 was observed in control group ; only grade 1

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no erythema with grade 2 was observed in control group

Range findings study reasults :

Intradermal induction: In order to respect the criteria for the selection of concentrations (the concentration should be well-tolerated systemically and locally, interdermal injections shold cause moderate irritant effect but no necrosis or ulceration of the skin), concentration chosen for the main study was 10% (w/w).

Application by cutaneous route: In order to respect the criteria for the selection of concentrations (the concentration should be well-tolerated systemically and locally, cutaneous application for the induction should cause at most weak of moderate skin reactions or be the maximal practicable concentration; cutaneous application for the challenge phase should be the highest concentration which does not cause irritant effect), concentratop, chosen for the topical application of the induction phase and for the challenge application was 100%.

Main study / Clinical examinations :

One animal of the treated group was found dead on day 19. No clinical sign was observed prior to death. As such spontaneous mortality is sometimes observed in this species, it was not attributed to treatment with the test substance. No clinical signs and no other mortality were observed during the study.

The bodyweight gain of the treated animals was similar to that of the control animals.

Cutaneous reactions

On day 10, after the cutaneous application of the induction period, signs of irritation were observed at the interscapular region in the control and treated group.

After challenge application, a very slight erythema (grade 1) was observed in all the animals of the control group.

In the treated group, at the 24 -hours reading, a very slight or well-defined erythema was noted in 1/19 and 18/19 animals, respectively. A slight edema was recorded in 6/19 animals. A the 48 -hour reading, a very sight well-defined or moderate erythema was noted in 1/19, 10/19 and 7/19 animals, respectively. A slight oedema was observed in 12/19 animals. Dryness of the skin was noted in 1/10 animals of the control group and in 12/19 animals of the treated group.

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Under the experimental conditions and according to the maximization method of Magnusson and Kligman, the test substance n-octyl acrylate induces delayed contact hypersensitivity in 100% guinea-pigs.

Executive summary:

The potential of the test substance, n-octyl acrylate to induce delayed contact hypersensitivity was evaluated in guinea-pigs according to the maximalisation method of Magnusson and Kligman and to the OECD 406 test guidelines.

Thirty guinea-pigs were allocated to two groups: a control group 1 (5M/5F) and a treated group 2 (10M/10F). On Day 1, intradermal injections of Freund's complete adjuvant mixed with the test substance (treated group, 10%) or the vehicle (control group) were performed in the intrascapular region. On Day 7, the same region received a topical application of sodium lauryl sulfate in vaseline (10%, w/w) in order to induce local irritation. On Day 8, the test substance (treated group, undiluted) or the vehicle (control group) was applied to the same test site which was then covered by an occlusive dressing for 48 hours. On Day 22, after a rest period of 12 days, all animals of the treated (undiluted) and control groups were challenged by a cutaneous application of the test substance to the right flank. The left flank served as control and received the vehicule only. Test substance and vehicle were maintained under an occlusive dressing for 24 hours. Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing. At the end of the study, animals were killed without examination of internal organs. Skin samples were taken from the challenge application sites of all the animals. No histological examination was performed.

No clinical signs were noted during the study. One treated male was found dead during the study; this death was not related to treatment.

After the challenge application, a very slight erythema was observed in all the animals of the control group. In the treated group, at the 24 -hours reading, a very slight or well-defined erythema was noted in 1/19 and 18/19 animals, respectively. A slight edema was recorded in 6/19 animals. A the 48 -hour reading, a very sight well-defined or moderate erythema was noted in 1/19, 10/19 and 7/19 animals, respectively. A slight oedema was observed in 12/19 animals. Dryness of the skin was noted in 1/10 animals of the control group and in 12/19 animals of the treated group. As the cutaneous reactions observed in the animals of the treated groups were of higher severity than those recorded in the animals of the control group, they were attributed to the sensitizing potential of the test substance.

The species and strain used showed a satisfactory sensitization response in 90% animals treated with DNCB.

In conclusion, under the experimental conditions and according to the maximization method of Magnusson and Kligman, the test substance n-octyl acrylate induces delayed contact hypersensitivity in 100% guinea-pigs.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

October / November 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

To determine the sensitizing potential of a test article when applied dermally as described in Development of the Mouse ear swilling test as on alternative dermal sensitization model: SC Grad, BJ Dunn and DW Dobbs, Department of Toxicology, Allied Corporation, Morristown, new Jersey.

GLP compliance:

yes

Type of study:

mouse ear swelling test

Justification for non-LLNA method:

This old study on mice was available before substance registration. No new test on animals was performed.

Species:

mouse

Strain:

Swiss Webster

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation:o data
- Weight at study initiation:o data
- Housing: 5/cage in suspended wire mesh cages.
- Diet (e.g. ad libitum): fresh purina rodent chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days
- Indication of any skin lesions: o data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled, no details
- Humidity (%): no data
- Air changes (per hr):o data
- Photoperiod (hrs dark / hrs light):o data

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.10 ml

Day(s)/duration:

4 consecutive days

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: acetone (50%)

Concentration / amount:

0.01 ml

Day(s)/duration:

one Day 9

No. of animals per dose:

Prelim : 2 animals
Main : 15 animals (10 treated, 5 control)

Details on study design:

Site preparation: Prior to tthe first dose, the abdominal area of each animal was clipped free of hair with an Oster Model 2 Clipper. The area was then stripped ten times with a fresh piece of dermaclearRtpe or a suitable substitute of tape. Following the tape stripping, each animal was administered two intradermal injections of Freunds complete adjuvant, used as 1:1 mixture in distilled water. Prior to the second, thrid and fourth doses, the abdominal area was stripped five times with tape.

Preliminary screen: A preliminary screen was performed to determine a minimally irritating and a nn-irritating concentration of the test article. Following the procedures used for induction and chanllenge dosing, the abdomen was dosed topically on Days 0, 1,2 and 3 and the ears were dosed topically on day 3.

Main study: the ear thickness of both ears of each mouse was measured at 24 and 48 hours folowing the challenge using a Peacock thikness gauge. Ether was used to anesthetize the mice to facilitate the ear swelling measurement. All mice were observed once daily for mortality and toxicity.
Analysis of data: An increase of 20µ or more in ear size is indicative of a sensitizing response.

Challenge controls:

no

Positive control substance(s):

no

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

2

Total no. in group:

10

Clinical observations:

no

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

1

Total no. in group:

9

Clinical observations:

no

Remarks on result:

positive indication of skin sensitisation

Cellular proliferation data / Observations:

In test group, positive response (a difference between the test ear and control ear of 20% of greater) was observed in 2/10 mice 24 hours after challenge (range of 0 to 26.1%) and 1/9 mice at 48 hours (range of 7.7 to 31.8%). In control group, percent ear swelling among the control animals ranged from 0 to 12%. One test animal died on Day 10 of the study. This death appeared to be directly related to the anesthetization procedure used during ear measuring and does not indicate test article toxicity.

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

According to this mouse ear swilling test, the test item is considered to be a skin sensitizer.

Executive summary:

Fifteen healthy female swiss webster mice were dosed topically with test item. Ten of the mice were dosed with 0.10 ml of the test article one time daily for 4 consecutive days in an attempt to induce a sensitizing response. Six days after the last induction treatment all fifteen mice were challenged with 0.01 ml of the test article on the left ear and the vehicle on the right ear. An increase of 20% or more in ear size was indicative of a sensitizing response.

In test group, positive response (a difference between the test ear and control ear of 20% of greater) was observed in 2/10 mice 24 hours after challenge (range of 0 to 26.1%) and 1/9 mice at 48 hours (range of 7.7 to 31.8%). In control group, percent ear swelling among the control animals ranged from 0 to 12%. One test animal died on Day 10 of the study. This death appeared to be directly related to the anesthetization procedure used during ear measuring and does not indicate test article toxicity.

Under the conditions of the study, the test article is a sensitizer.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

A mouse ear swilling test on the reaction mass of actyl and decyl acrylate (1985)

Fifteen healthy female swiss webster mice were dosed topically with test item. Ten of the mice were dosed with 0.10 ml of the test article one time daily for 4 consecutive days in an attempt to induce a sensitizing response. Six days after the last induction treatment all fifteen mice were challenged with 0.01 ml of the test article on the left ear and the vehicle on the right ear. An increase of 20% or more in ear size was indicative of a sensitizing response.

In test group, positive response (a difference between the test ear and control ear of 20% of greater) was observed in 2/10 mice 24 hours after challenge (range of 0 to 26.1%) and 1/9 mice at 48 hours (range of 7.7 to 31.8%). In control group, percent ear swelling among the control animals ranged from 0 to 12%. One test animal died on Day 10 of the study. This death appeared to be directly related to the anesthetization procedure used during ear measuring and does not indicate test article toxicity. Under the conditions of the study, the test article is a sensitizer.

GPMT on octyl acrylate (1999) / Read-across

The potential of the test substance, n-octyl acrylate to induce delayed contact hypersensitivity was evaluated in guinea-pigs according to the maximalisation method of Magnusson and Kligman and to the OECD 406 test guidelines.

Thirty guinea-pigs were allocated to two groups: a control group 1 (5M/5F) and a treated group 2 (10M/10F). On Day 1, intradermal injections of Freund's complete adjuvant mixed with the test substance (treated group, 10%) or the vehicle (control group) were performed in the intrascapular region. On Day 7, the same region received a topical application of sodium lauryl sulfate in vaseline (10%, w/w) in order to induce local irritation. On Day 8, the test substance (treated group, undiluted) or the vehicle (control group) was applied to the same test site which was then covered by an occlusive dressing for 48 hours. On Day 22, after a rest period of 12 days, all animals of the treated (undiluted) and control groups were challenged by a cutaneous application of the test substance to the right flank. The left flank served as control and received the vehicule only. Test substance and vehicle were maintained under an occlusive dressing for 24 hours. Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing. At the end of the study, animals were killed without examination of internal organs. Skin samples were taken from the challenge application sites of all the animals. No histological examination was performed.

No clinical signs were noted during the study. One treated male was found dead during the study; this death was not related to treatment.

After the challenge application, a very slight erythema was observed in all the animals of the control group. In the treated group, at the 24 -hours reading, a very slight or well-defined erythema was noted in 1/19 and 18/19 animals, respectively. A slight edema was recorded in 6/19 animals. A the 48 -hour reading, a very sight well-defined or moderate erythema was noted in 1/19, 10/19 and 7/19 animals, respectively. A slight oedema was observed in 12/19 animals. Dryness of the skin was noted in 1/10 animals of the control group and in 12/19 animals of the treated group. As the cutaneous reactions observed in the animals of the treated groups were of higher severity than those recorded in the animals of the control group, they were attributed to the sensitizing potential of the test substance.

The species and strain used showed a satisfactory sensitization response in 90% animals treated with DNCB.

In conclusion, under the experimental conditions and according to the maximization method of Magnusson and Kligman, the test substance n-octyl acrylate induces delayed contact hypersensitivity in 100% guinea-pigs.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

A skin sensitisation study in available on the reaction mass of decyl and octyl acrylate leading to a classification as skin sensitisating. But no sub-category can be determined based on this study.

Data on octyl acrylate (a constituant substance of the reaction mass) was used to determine this sub-category : positive results in GPMT with an intradermal induction of 10% and 100% of reaction : a subcategory "1B" is required.

At the end, the registered substance (reaction mass of decyl and octyl acrylate) is considered to be a skin sensitizer according to the Regulation EC no.1272/2008 and should be classified as Skin sens.1B (H317).