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EC number: 221-950-4 | CAS number: 3290-92-4
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From April 29 to June 15, 1996
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
- Report date:
- 1996
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- yes
- Remarks:
- no certificate of analysis, no data on animal gender and purity of test substance
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The guinea-pigs study was performed before the REACH regulation.
Test material
- Reference substance name:
- Propylidynetrimethyl trimethacrylate
- EC Number:
- 221-950-4
- EC Name:
- Propylidynetrimethyl trimethacrylate
- Cas Number:
- 3290-92-4
- Molecular formula:
- C18H26O6
- IUPAC Name:
- 2,2-bis[(methacryloyloxy)methyl]butyl methacrylate (non-preferred name)
- Test material form:
- other: Colourless liquid
- Details on test material:
- - Name of test material : TMPTMA
- Physical state: Colourless liquid
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- not specified
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 312-490 g
- Housing: Housed singly or in pairs in solid-floor polypropylene cages
- Diet (e.g. ad libitum): Guinea Pig FD1 Diet (Special Diets Services Limited, Witham, UK), ad libitum
- Water (e.g. ad libitum): Mains tap water, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 °C
- Humidity (%): 45-68%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal and epicutaneous
- Vehicle:
- arachis oil
- Concentration / amount:
- Range finding test:
- Intradermal induction exposure: 1, 5, 10 or 25% w/v in arachis oil
- Topical induction exposure: 25, 50, 75 or 100% w/v in arachis oil
- Topical challenge exposure: 25, 50, 75 or 100% w/v in arachis oil
Main test:
- Intradermal induction exposure: 25% w/v in arachis oil
- Topical induction exposure: Undiluted
- Topical challenge exposure: 75 or 100% w/v in arachis oil
Challengeopen allclose all
- Route:
- epicutaneous, occlusive
- Vehicle:
- arachis oil
- Concentration / amount:
- Range finding test:
- Intradermal induction exposure: 1, 5, 10 or 25% w/v in arachis oil
- Topical induction exposure: 25, 50, 75 or 100% w/v in arachis oil
- Topical challenge exposure: 25, 50, 75 or 100% w/v in arachis oil
Main test:
- Intradermal induction exposure: 25% w/v in arachis oil
- Topical induction exposure: Undiluted
- Topical challenge exposure: 75 or 100% w/v in arachis oil
- No. of animals per dose:
- Range finding test:
- Intradermal induction exposure: 1 animal/dose
- Topical induction and challenge exposure: 2 animals/dose
Main test: 10 and 20 animals for control and test, respectively - Details on study design:
- RANGE FINDING TESTS:
- Intradermal induction exposure: Guinea pigs (1/dose) received injections (0.1 mL) of test material at concentrations of 1, 5, 10 or 25% w/v in arachis oil and observed for systemic toxicity and erythema scores (Draize scoring system) at 24, 48 and 72 hours and 7 days.
- Topical induction exposure: Two guinea pigs [intradermally injected with Freund's Complete Adjuvant (FCA) 16 days earlier] applied with test material at concentrations of 25, 50, 75 or 100% v/v in arachis oil for 48 hours and observed for erythema and oedema at 1, 24 and 48 hours.
- Topical challenge exposure: Two guinea pigs applied with test material at concentrations of 25, 50, 75 or 100% v/v in arachis oil for 24 hours and observed for erythema and oedema at 1, 24 and 48 hours.
MAIN STUDY
A. INDUCTION EXPOSURE: INTRADERMAL
- No. of exposures: One
- Test groups: Intradermally injected with 0.1 mL of FCA, 25% w/v test material in arachis oil and 25% w/v test material emulsion in FCA on Day 0
- Control group: Intradermally injected with FCA, arachis oil or 50% w/v arachis oil in FCA on Day 0
- Site: Shoulder region on each side of mid-line
- Duration: Days 0-6
B. INDUCTION EXPOSURE: TOPICAL
- No. of exposures: One
- Exposure period: 48 hours
- Test groups: Filter paper patch saturated with undiluted test material topically applied on Day 7 via occlusive patch
- Control group: Only filter paper patch topically applied on Day 7 via occlusive patch
- Site: Shoulder region on each side of mid-line
- Frequency of applications: Single application
- Duration: Days 7-21
C. CHALLENGE EXPOSURE: TOPICAL
- No. of exposures: One
- Day of challenge: Day 21
- Exposure period: 24 hours
- Test groups: Filter paper patch saturated with 75 or 100% v/v test material in arachis oil topically applied on Day 21 via occlusive patch
- Site: 75 or 100% v/v in arachis oil was applied to left or right shorn flank, respectively
- Evaluation (hour after removal of challenge patch): 24 or 48 hours - Challenge controls:
- No data
- Positive control substance(s):
- yes
- Remarks:
- Historical data: Ethyl 4-aminobenzoate 98%; 2,4-Dinitrochlorobenzene; Neomycin sulphate; 2-Mercaptobenzothiazole
Results and discussion
- Positive control results:
- Historical data (August 1994 to February 1996):
- Incidence of sensitisation for 98% ethyl 4-aminobenzoate, 2,4-dinitrochlorobenzene, neomycin sulphate, 2-mercaptobenzothiazole were 39% (7/18), 100% (9/9), 100% (10/10), 60% (12/20) or 70% (7/10), respectively
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 75 or 100% v/v in arachis oil
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 75 or 100% v/v on arachis oil
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Group:
- positive control
- No. with + reactions:
- 7
- Total no. in group:
- 10
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- (2-mercaptobenzothiazole)
Any other information on results incl. tables
Table 1: Intradermal sighting test - summary of results
Animal identification |
Time of observation |
Concentration of test material (% w/v) |
Grade of erythema at Injection Sites |
Evidence of systemic toxicity |
A |
24 hours |
1 |
1 |
None |
48 hours |
2 |
None |
||
72 hours |
3 |
None |
||
7 days |
0 |
None |
||
B |
24 hours |
5 |
1 |
None |
48 hours |
2 |
None |
||
72 hours |
3 |
None |
||
7 days |
0 |
None |
||
E |
24 hours |
10 |
1 |
None |
48 hours |
1 |
None |
||
72 hours |
1 |
None |
||
7 days |
1 |
None |
||
F |
24 hours |
25 |
2 |
None |
48 hours |
2 |
None |
||
72 hours |
2 |
None |
||
7 days |
1 |
None |
Conclusion: The concentration of the test material selected for the intradermal induction stage of the main study was 25% w/v in arachis oil BP
Table 2: Topical sighting test for induction application (48-hour exposure) - individual skin reactions
Animal identification |
Concentration of test material (% v/v) |
Skin Reactions (Hours After Removal of Patches) |
||||||||
1 |
24 |
48 |
||||||||
Er |
Oe |
Other |
Er |
Oe |
Other |
Er |
Oe |
Other |
||
G |
100 |
2 |
1 |
- |
1 |
0 |
- |
0 |
0 |
- |
75 |
2 |
1 |
- |
1 |
0 |
- |
0 |
0 |
- |
|
50 |
2 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
25 |
1 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
H |
100 |
2 |
0 |
- |
2 |
0 |
- |
1 |
0 |
- |
75 |
2 |
0 |
- |
1 |
0 |
- |
0 |
0 |
- |
|
50 |
1 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
25 |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
Conclusion: The undiluted test material was selected for the main study topical induction
Table 3: Topical sighting test for challenge application (24-hour exposure) - individual skin reactions
Animal identification |
Concentration of test material (% v/v) |
Skin Reactions (Hours After Removal of Patches) |
||||||||
1 |
24 |
48 |
||||||||
Er |
Oe |
Other |
Er |
Oe |
Other |
Er |
Oe |
Other |
||
I |
100 |
1 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
75 |
1 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
50 |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
25 |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
J |
100 |
1 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
75 |
1 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
50 |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
25 |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
Er = erythema; Oe = oedema; - = no other reactions noted
Conclusion: The concentrations of the test material selected for the main study topical challenge were 100 and 75% v/v in arachis oil BP
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Remarks:
- not skin sensitizing
- Conclusions:
- Under these test conditions, TMPTMA is not a skin sensitiser and is not classified according to the CLP Regulation (EC) N° (1272-2008).
- Executive summary:
In a Magnusson & Kligman maximisation study (GPMT) performed according to OECD guideline 406 and in compliance with GLP, groups of 20 albino Dunkin Hartley guinea pigs were intradermally induced with three injections of 0.1 mL of FCA, 25% w/v TMPTMA in arachis oil and 25% w/v TMPTMA emulsion in FCA on Day 0 on shoulder region on each side of mid-line. After one week the same area were topically induced with 0.2 mL of undiluted test material via occluded filter paper patch for 48 hours. After 2 weeks of rest period, a challenge patch of 75 or 100% v/v test material in arachis oil was applied to left or right shorn flank, respectively. Control groups of 10 animals was included and treated with FCA, arachis oil or 50% w/v arachis oil in FCA. The test concentrations for the main study were determined from a sighting study using two animals.
Intradermal and topical induction indicated evidence of dermal irritation. No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-hour observations. TMPTMA produced a 0% (0/20) sensitisation rate and was considered to be a nonsensitiser to guinea pig skin. Historical data on positive controls (ethyl 4-aminobenzoate 98%; 2,4-dinitrochlorobenzene; neomycin sulphate; 2-mercaptobenzothiazole) exhibited evidence of sensitisation, thus confirming the susceptibility of this group of animals to dermal sensitisation.
Under these test conditions, TMPTMA is not classified according to the Annex VI to the CLP Regulation (EC) N° 1272-2008.
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