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Administrative data

Description of key information

The results of skin and eye irritation studies with trimethylolpropane diallyl ether (TMPDE) show that the substance is a mild irritant but do not trigger classification of the substance as a skin or eye irritant according to EEC Council Directive 79/831/EEC Annex VI, Part II (D) as described in Commission Directive 93/21/EEC or Regulation (EC) No 1272/2008.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
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
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)
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 hosued 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.
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 the rabbits were clipped free of fur from the dorsal flank using veterinary clippers. Only animals with a healty 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 cm x 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 sistes 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.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 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.

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 to 9 July 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary GLP guideline-compliant study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The animals were three New Zealand White rabbits supplied by David Percival Ltd., Cheshire, UK. The animals weighed 2.20 to 2.53 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 hosued 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 59-65%. There were approximately 15 air changes per hour, and lighting was controlled to give 12 hours light and 12 hours darkness.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml was instilled into the right eye
Duration of treatment / exposure:
Single administration
Observation period (in vivo):
72 hours following treatment
Number of animals or in vitro replicates:
3 females
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Animals showing evidence of ocular lesions were rejected and replaced.
One rabbit was initially treated, 0.1 ml test substance was instilled into the conjunctival sac of the right eye. The upper and lower lids were held together for about 1 second immediately after instillation, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration, an assessment of the initial pain reaction was made.
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. In order to minimise pain on instillation, one drop of local anaesthetic ("Ophthaine") was instilled into both eyes of these animals 1-2 minutes before treatment.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation 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". Examination of the eye was facilitated by the use of light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Residual test material was noted around the treated eye of all animals one hour after treatment.
Diffuse corneal opacity was noted in two treated eyes at the 24 and 48 hour observations. No other corneal effects were noted. Iridial effects were noted. Minimal conjunctival irritation was noted in all treated eyes one hour after treatment with minimal to moderate conjunctival irritation at the 24 hour observation. Minimal conjunctival redness was noted in two treated eyes at the 48 hour observation.
Treated eyes appeared normal 48 or 72 hours after treatment. Individual animal data are presented in Table 1.
Other effects:
No other effects reported.

Table 1. Individual ocular irritation scores

Rabbit Number & Sex (Bodyweight Kg)

Time After Treatment

Corneal Opacity

Iridial Inflammation

Conjunctival Redness

Conjuncitval Chemosis

95 Female (2.20)

24 hours

0

0

1

0

48 hours

0

0

0

0

72 hours

0

0

0

0

Total

0

0

1

0

Mean

0.0

0.0

0.3

0.0

 

96 Female (2.53)

24 hours

1

1

2

1

48 hours

1

0

1

0

72 hours

0

0

0

0

Total

2

1

3

1

Mean

0.7

0.3

1.0

0.3

 

99 Female (2.20)

24 hours

1

1

2

2

48 hours

1

0

1

0

72 hours

0

0

0

0

Total

2

1

3

2

Mean

0.7

0.3

1.0

0.7

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was found to be a mild eye irritant under the conditions of this study, the severity of the effects does not trigger classification of the substance as an eye irritant under CLP Regulation (EC) No 1272/2008.
Executive summary:

The eye irritant potential of TMPDE (NEOALLYL T-20) was assessed in three New Zealand White rabbits according to OECD method 405. A single instillation of the test material to the non-irrigated eye produced diffuse corneal opacity, iridial inflammation and minimal to moderate conjunctival irritation. Treated eyes appeared normal 72 hours after treatment and the severity of the effects does not trigger classification of the substance as an eye irritant under CLP Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The results of a skin irritation study with trimethylolpropane diallyl ether (TMPDE) show the substance to be a mild irritant (Driscoll, 1993). The results of a an eye irritation study with TMPDE show the substance to be a mild irritant (Driscoll, 1993).

The results of two studies conducted by Bayer AG Leverkusen in rabbits also demonstrated that TMPDE is moderately irritating to skin, and not irritating to eyes. The original study reports are not available, results are quoted from the IUCLID dataset (2000) and are presented in support of the data summarised above.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available

Justification for classification or non-classification

The results of studies with TMPDE do not trigger classification of the substance as a skin or eye irritant according to EEC Council Directive 79/831/EEC Annex VI, Part II (D) as described in Commission Directive 93/21/EEC or Regulation (EC) No 1272/2008.