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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 June to 1 August 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary GLP guideline-compliant study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
The animals were female albino Dunkin-Hartley guinea pigs, supplied by David Hall Ltd., UK. The animals weighed 348-426 g at the start of the study, and were approximately 8-12 weeks old. They were acclimatised for at least 5 days. Individuals were identified by unique numbers written onto a small area of clipped rump using indelible marker pen.
The animals were housed in groups of up to three in solid-floor polypropylene cages furnished with softwood shavings. Free access to mains tap water and food (Guinea Pig FD1 Diet, SDS Ltd., UK) was allowed throughout the study. The animal room was maintained at a temperature of 20-23°C and relative humidity of 46-70%. There were approximately 15 air changes per hour, and the lighting was controlled to provide 12 hours light and 12 hours darkness.
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Intradermal induction: 10% solution in arachis oil B.P.
Topical induction: undiluted test material
Challenge: undiluted test material and 75% (v/v) in arachis oil B.P.
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Intradermal induction: 10% solution in arachis oil B.P.
Topical induction: undiluted test material
Challenge: undiluted test material and 75% (v/v) in arachis oil B.P.
No. of animals per dose:
10 test guinea pigs and 10 control guinea pigs
Details on study design:
Range finding study:
The concentrations of test material to be used at each stage of the main study were determined by range finding tests.
Four animals were intradermally injected with preparations of test material (1%, 5%, 10% or 25% w/v in arachis oil B.P.). The highest concentration that did not cause local necrosis, ulceration or systemic toxicity was selected for the intradermal induction stage of the main study.
Two animals (intradermally injected with Freunds Complete Adjuvant (FCA) 10 days earlier) were treated with the undiluted test material and 3 preparations of the test material (75%, 50% and 25% v/v in arachis oil B.P.). The highest concentration producing only mild to moderate dermal irritataion after a 72 hour occlusive exposure, was selected for the topical induction stage of the main study.
The undiluted test material and a preparation of the test material (75% v/v arachis oil B.P.) were applied for a period of 24 hours. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study, up to Day 14. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.

Main study:
Shortly before treatment on Day 0 the hair was removed from an area approximately 40 mm x 60 mm on the shoulder region of each animal with veterinary clippers. A row of three injections (0.1 ml each) was made on each side of the midline as follows:
1. FCA in distilled water 1:1
2. 10% (w/v) dilution of test material in arachis oil B.P.
3. 10% (w/v) dilution of test material in a 1:1 preparation of FCA plus arachis oil B.P.
On Day 6, the nuchal region was clipped and shaved. A volume of 0.5 ml of sodium laurylsulphate (10% w/w in petrolatum) was applied in order to provoke an inflammatory response. The treatment sites remained non-occluded.
On Day 7, the same area on the shoulder region used previously for intradermal injections was clipped again and treated with a topical application of undiluted test material. The undiluted test material (0.2-0.3 ml) was applied on filter paper (Whatman No. 4) which was held in place by a strip of surgical adhesive tape (Blenderm), and covered with an overlapping length of aluminium foil. The patch and foil were further secured by a strip of elastic adhesive bandage (Elastoplast) wound in a double layer around the torso of each animal. This occlusive dressing was kept in place for 48 hours.
The sites were scored for erythema formation 1 and 24 hours following removal of the patches.

Shortly before treatment on Day 21, an area approximately 50 mm x 70 mm on both flanks of each animal, was clipped free of hair with veterinary clippers. A quantity of 0.1-0.2 ml of the undiluted test substance was applied to the shorn right flank of each animal on a square of filter paper, held in place by surgical adhesive tape. To ensure that the maximum non-irritant concentration was used at challenge, the test material at a concentration of 75% (v/v) in arachis oil B.P. was also similarly applied to a separate skin site on the right shorn flank. The vehicle alone was similarly applied to a separate skin site on the right shorn flank. The patches were occluded with an overlapping length of aluminium foil and secured by Elastoplast. After 24 hours, the dressing was removed. The challenge sites were swabbed with cotton wool soaked in diethyl ether to remove residual material. The vehicle sites were also swabbed. The position of the treatment sites was identified by using a black indelible marker pen. Prior to the 24 hour observation, the flanks were clipped using veterinary clippers to remove regrown hair. Skin reactions were scored 24 and 48 hours after patch removal.
Challenge controls:
Intradermal injections were administered using an identical procedure to that used for the test animals, except the injections were:
1. FCA in distilled water 1:1
2. arachis oil B.P.
3. FCA in arachis oil B.P. 1:1
The topical applications followed the same procedure as for the test animals except that nothing was applied to the filter paper. Skin reactions were quanitified as for the test animals.
The controls were challenged in an identical manner to the test animals.
Positive control substance(s):
yes
Remarks:
DNCB
Positive control results:
A positive control was not examined.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Scattered mild redness was elicited by the test material after topical induction. No skin reaction were noted at the challegne sites and vehicle control sites of the test or control group animals at the 24 and 48 hour observations.

Bodyweight gains of the guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group animals over the same period.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The test substance produced a 0% (0/10) sensitisation rate and can therefore be considered to be non-sensitising to guinea pigs.
Executive summary:

The skin contact sensitisation potential of TMPDE (NEOALLYL T-20) was determined in female albino guinea pigs, according to OECD method 406 (Magnusson and Kligman Maximisation Test). Based on the results of a range-finding study, the concentrations of test material for the induction and challenge phases were: Intradermal induction - 10% (w/v) in arachis oil B.P.; Topical induction - undiluted as supplied; Topical challenge - undiluted as supplied and 75% (v/v) in arachis oil B.P. Scattered mild redness was elicited by the test material after topical induction. The test material produced a 0% (0/10) sensitisation rate and can therefore be classified as a non-sensitiser to guinea pig skin. A reliability check using DNCB confirmed the sensitivity of the assay.

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

No evidence of skin sensitisation was seen in a guideline-compliant Maximisation assay performed with trimethylolpropane diallyl ether (Driscoll, 1993).


Migrated from Short description of key information:
A Maximisation assay performed with trimethylolpropane diallyl ether.

Justification for selection of skin sensitisation endpoint:
Only one study available

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No evidence of skin sensitsation was seen in a Maximisation assay performed with trimethylolpropane diallyl ether.


Migrated from Short description of key information:
There is no indication from reports in exposed workers that the substance can cause respiratory sensitisation (occupational asthma).

Justification for classification or non-classification

TMPDE is not classified as a skin sensitiser on the basis of the data available. There is no indication from reports in exposed workers that the substance can cause skin or respiratory sensitisation.