Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
24 July 2013 - 14 August 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study OECD 429, GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
individual approach (adopted 22 July 2010)
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
dated May 30, 2008
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
Identification: Isobutyl methacrylate
Origin: Evonik Industries AG, Darmstadt
Batch: 730514T40
Purity: 99.83% stabilised with 99 ppm HQME
Expiry Date: 20 December 2013
Storage Conditions:
(provided by the Sponsor) Room temperature

Species:
mouse
Strain:
other: Mice, CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- CBA/CaOlaHsd mice, nulliparous, non-pregnant
- Age at study initiation: 9 - 10 weeks (beginning of treatment)
- Weight at study initiation: 21.7 g ± 1.5 g
- Housing: single; Makrolon Type I, with wire mesh top
- Diet (e.g. ad libitum):2018C Teklad Global 18% protein rodent diet (certified), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 45-94 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
1 (Control ) 0
2 (Low Dose) 25% (w/v)
3 (Mid Dose) 50% (w/v)
4 (High Dose) 100% (w/v)
No. of animals per dose:
Main study: 5 females (nulliparous and non-pregnant)
Pre-test: 2 females
Details on study design:
RANGE FINDING TESTS:
Concentrations were tested on two mice on one ear each.
From day 2 up to day 6, the animal treated with 50% test item concentration showed an erythema of the ear skin (Score 1). From day 2 up to day 4 and on day 6 the animal treated with 100% test item concentration showed an erythema of the ear skin (Score 1). On day 5, the animal treated with 100% test item concentration showed an erythema of the ear skin (Score 2). In addition, the erythema of the animal treated with 100% test item concentration was scabby on day 5 and 6.
Thus, the test item in the main study was assayed at 25, 50 and 100%. The highest concentration tested was the highest level that could be achieved whilst avoiding systemic toxicity and excessive local skin irritation as confirmed in the pre-experiment.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations were calculated in the body weight tables and for the DPM values (group mean DPM ± standard deviation).
The Dean-Dixon-Test was used for identification of possible outliers (performed with Microsoft Excel 2007).
However, both biological and statistical significance were considered together.
Positive control results:
A positive control performed with alpha-Hexylcinnamaldehyd in April 2013 resulted in an S.I. of 1.6 at 5% (w/v)
alpha-Hexylcinnamaldehyd in acetone/olive oil (4+1, v/v), 2.4 at 10 % and 5.9 at 25 %. An EC3 of 12.6% was calculated.
Parameter:
SI
Value:
1.78
Test group / Remarks:
25 %
Remarks on result:
other: DPM/lymph node: 229.5
Key result
Parameter:
SI
Value:
3.64
Test group / Remarks:
50 %
Remarks on result:
other: DPM/lymph node: 469.1
Key result
Parameter:
SI
Value:
5.13
Test group / Remarks:
100 %
Remarks on result:
other: DPM/lymph node: 661.9
Parameter:
EC3
Value:
41.4

Calculation and Results of Individual Data

Vehicle: acetone/olive oil (4+1 v/v)

Test item concentration

DPM values measured

DPM-BG per animal
(2 lymph nodes)a)

S.I.b)

%

Group no.

Animal no.

---

---

BG I

22

---

---

---

---

BG II

25

---

---

0

1

1

108

84.5

---

0

1

2

176

152.5

---

0

1

3

99

75.5

---

0

1

4

129

105.5

---

0

1

5

250

226.5

---

25

2

6

214

190.5

1.5

25

2

7

261

237.5

1.8

25

2

8

255

231.5

1.8

25

2

9

134

110.5

0.9

25

2

10

401

377.5

2.9

50

3

11

430

406.5

3.2

50

3

12

563

539.5

4.2

50

3

13

644

620.5

4.8

50

3

14

443

419.5

3.3

50

3

15

383

359.5

2.8

100

4

16

731

707.5

5.5

100

4

17

775

751.5

5.8

100

4

18

659

635.5

4.9

100

4

19

689

665.5

5.2

100

4

20

573

549.5

4.3

1    =  Control Group

2-4=  Test Group

a)   =  values corrected for mean background value (BGI and BGII)

b)    =  Stimulation Indices relative to the mean of the control group (Group 1)

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP EU GHS (Regulation (EC) No 1272/2008
Conclusions:
In this Local Lymph Node Assay Isobutyl methacrylate is a dermal sensitiser.
CLP EU GHS (Regulation (EC) No 1272/2008) classification: sensitizing category 1B (EC3 value > 2%)
Executive summary:

In a dermal sensitisation study according to OECD Guideline 429 (adopted July 2010) Isobutyl methacrylate in acetone:olive oil (4+1, v/v), groups of 5 female CBA/CaOlaHsd mice were tested using the LLNA method with the individual approach.

In this Local Lymph Node Assay Isobutyl methacrylate is a dermal sensitiser.

 

No clinical signs and no systemic findings were observed after the first and second application (25% and 50%). Only the highest dose (100%) induced slight erythema on the ear skin of all four animals of the group.

The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age. No cases of mortality were observed.

STIMULATION INDICES (S.I.) of 1.78, 3.64, and 5.13 were determined with the test substance at concentrations of 25%, 50% and 100% (w/v) in acetone:olive oil (4+1, v/v), respectively. The positive control substance wasα-Hexylcinnamaldehyde, which gave an EC3 at 5.9 % (w/v). A result is regarded as positive when the S.I. is ≥3.

Based on these criteria, the test substance was found to be a sensitiser. The EC3 was calculated to be 41.4 %.

In this study, Isobutyl methacrylate is a dermal sensitiser.

CLP EU GHS (Regulation (EC) No 1272/2008) classification: sensitizing category 1B (EC3 value > 2%)

 

 

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a

publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is

reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the

data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Data availability

For isobutyl methacrylate a sensitization test in Guinea pigs according to the maximization protocol and a mouse local lymphnode assay are available. There are no relevant human case studies.

Animal experiments

The delayed contact hypersensitivity of isobutyl methacrylate was evaluated in Guinea pigs according to OECD N°406 guideline (Magnusson and Kligman test) (Poole, 1980). The induction phase has been realized both by intradermal route on day 1 (2% in FCA as well as in liquid paraffin) and by cutaneous route on day 7 (undiluted for 48 h). The challenge was performed using 10 % i-BMA in petrolatum. There were no visible responses after 48 or 72 hours. Due to the fact that the M&K assay does not detect all known human contact allergens, although the test itself was negative, the substance was regarded as no worse than a weak contact allergen.

In a mouse local lymphnode assay isobutyl methacrylate formulated in acetone/olive oil (4+1 v/v) was assessed for its possible skin sensitising potential.
For this purpose a local lymph node assay was performed using test item concentrations of
 25, 50 and 100%.
All treated animals survived the scheduled study period and no signs of systemic toxicity were observed. On day 4, the animals treated with a test item concentration of 100% showed an erythema of the ear skin (Score 1).
Stimulation Indices (S.I.) of 1.78, 3.64 and 5.13 were determined with isobutyl methacrylate
 at concentrations of 25, 50 and 100% in acetone/olive oil (4+1 v/v), respectively. A clear dose response was observed.
The test item isobutyl methacrylate was found to be a skin sensitiser and an EC3 value of 41.4 % (w/v) was derived. In this study isobutyl methacrylate is a skin sensitizer of weak potency.

The closely related isomer n-butyl methacrylate was investigated in a delayed contact hypersensitivity test in Guinea pigs according to OECD N°406 guideline (Magnusson and Kligman test) (CIT, 2008). The induction phase has been realized both by intradermal route on day 1 (5% in corn oil) and by cutaneous route on day 8 (50% (w/w) in ethanol/purified water (80/20, w/w)) in 1 group of guinea pigs (2 males and 3 females). The challenge phase was realized on day 22 by cutaneous application of n-butyl methacrylate (10% (w/w) in acetone on the right flank (vehicle on the left flank); the cutaneous reactions were scored 24 and 48 hours after the challenge phase. After the challenge application, no cutaneous reactions were noted on the left flank (application of the vehicle) of the animals. On the right flank (application of n-butyl methacrylate) of the animals, a discrete or moderate erythema was noted in 4/5 and 2/5 animals at the 24 and 48-hour readings, respectively. An oedema and dryness of the skin were also noted in 1/5 and 2/5 animals, respectively, at the 48-hour reading. In conclusion, n-butyl methacrylate induced delayed contact hypersensitivity in 4/5 (80%) guinea pigs.

Human data

While n-BMA showed some evidence of skin sensitisation in humans, no relevant data are available for i-BMA.

Summary

In summary, taking into account the information available for isobutyl methacrylate and the structurally closely related isomer n-BMA, isobutyl methacrylate is regarded as a skin sensitiser of weak potency.


Migrated from Short description of key information:
Isobutyl methacrylate is expected to be a weak skin sensitiser

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No cases of respiratory allergy have been reported in the literature.

Justification for classification or non-classification

Based on the results of the local lymphnode assay with isobutyl methacrylate and the structurally closely related isomer n-BMA, it is considered that the substance comprises the potential for skin sensitisation and has therefore to be classified with R43/ skin sensitiser under 67/548/EEC and as a Cat. 1 skin sensitiser according to CLP (1272/2008/EC) and Cat 1B, skin sensitiser according to UN GHS (2009) requirements

Based on the available data there is no evidence that i-BMA causes respiratory sensitisation.Therefore, a classification for respiratory sensitisation is considered as not justified.