Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
30 June to 3 July 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary GLP guideline-compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
TMPDE. The trade name of the substance was NEOALLYL T-20, lot no. 30341, received on 7 June 1993. The substance was a mixture of Trimethylolpropane Diallyl Ether (87.4%), Trimethylolpropane Monoallyl Ether (6.9%), and Trimethylolpropane Triallyl Ether (5.7%). The purity was given as 100%. The substance was described as a colourless liquid, and was stored in a metal canister at 4°C in the dark.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
The animals were three New Zealand White rabbits supplied by David Percival Ltd., Cheshire, UK. The animals weighed 2.02 to 2.28 kg and were 12-16 weeks old at the start of the study, they were acclimatised for a minimum of 5 days. Individuals were identified by unique numbers written on the inner surface of the ear with an indelible black marker.
The rabbits were housed individually in suspended metal cages. Free access to mains drinking water and food (RABMA Rabbit 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 60-66%. There were approximately 15 air changes per hour, and lighting was controlled to give 12 hours light and 12 hours darkness.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml test substance was applied
Duration of treatment / exposure:
4 hours
Observation period:
72 hours following patch removal
Number of animals:
2 males and 1 female
Details on study design:
On the day before the test, rabbits were clipped free of fur from the dorsal flank using veterinary clippers. Only animals with a healthy intact epidermis (by gross observation) were selected for the study. On the day of the test, a suitable test site was selected on the back of each rabbit. A quantity of 0.5 ml of the test substance was introduced under a 2.5 × 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in place with a strip of surgical adhesive tape (Blenderm). The trunk of each rabbit was then wrapped in an elasticated corset (Tubigrip), and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed, and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether. Approximately 1 hour following patch removal, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation according to the scale from Draize (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics".
The scores for erythema and oedema at the 24 and 72 hour readings were totalled for the 3 rabbits, and divided by 6 to give the primary irritation index of the test material.

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 73 hour readings
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 48 hours in 2/3 rabbits
Irritant / corrosive response data:
Very slight erythema was noted at all treated skin sites 1 and 24 hours after patch removal, and at one treated skin site at the 48 hour observation. Very slight oedema was noted at two treated skin sites 1 hour after patch removal. Very slight oedema developed at one treated skin site at the 24 hour observation and persisted at the 48 hour observation. Desquamation was noted at one treated skin site at the 48 and 72 hour observations. Two treated skin sites appeared normal at the 48 hour observation. Individual readings are shown in Table 1.
Other effects:
No other effects were reported.

Any other information on results incl. tables

Table 1. Individual Skin Reactions

Skin Reaction

Reading (hours)

Individual Scores – Rabbit Number and Sex (Body weight Kg)

Total

69 Male (2.21)

72 Male (2.28)

79 Female (2.02)

Erythema/Eschar Formation

1

1

1

1R

(3)

24

1

1

1

3

48

1D

0

0

(1)

72

0D

0

0

0

Odema Formation

1

0

1

1

(2)

24

1

0

0

1

48

1

0

0

(1)

72

0

0

0

0

Sum of 24 and 72 hour Readings

                               4

Primary Irritation Index

                              0.7

( ) = Total values not used for calculation of primary irritation index

D = desquamation

R = reaction extending up to 4 cm beyond treatment site

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material did not produce positive criteria in any rabbit according to the EEC labelling regulations, and was classified as not irritating to rabbit skin.
Executive summary:

The skin irritant potential of TMPDE (NEOALLYL T-20) was determined in 3 New Zealand White Rabbits according to OECD method 404. Following a single 4 hour semi-occluded exposure on intact skin, the test material produced a primary irritation index of 0.7 and was classified as a mild irritant according to the Draize classification scheme. No corrosive effects were noted.

The test material was classified as a non-irritant according to EEC labelling regulations; no symbol and risk phrase are required.