Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating (US FHSA Federal regulation: 16 CFR 1500.41, pre-GLP), applied to intact and abraded skin for

24 h under occlusive dressing; no skin reaction on intact skin
Eye irritation: not irritating (OECD guideline 405, GLP), slight redness in 1/3 animals after 1 h; no effects after 24, 48,

72 h

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
Guideline:
other: Appraisal of the safety of chemicals in foods, druge and cosmetics, by the Staft of the Division of Pharmacology, US FDA, skin toxicity according to Draize (1959)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
other: US FHSA Federal regulation: 16 CFR 1500.41
Deviations:
no
GLP compliance:
no
Remarks:
study performed before implementation of GLP
Specific details on test material used for the study:
- Name of test material (as cited in study report): Triethylenglykoldimethacrylat
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.4 to 2.6 kg
- Housing: individually
- Diet (e.g. ad libitum): standard diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C
- Humidity (%):45 to 55%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
other: one site shaved/intact + one site shaved/abraded
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated control sites on the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): used as suppplied


Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
6
Details on study design:
TEST SITE
- The test material was applied to two clipped areas on each of six animals, one abraded and one left intact.
- Area of exposure: 2.5 x 2.5 cm
- Coverage ad wrap: Test sites were covered with medical strips which were fixed by leucoplast stripes. Whole animal trunk was wrapped in rubberized impervious cloth to minimize evaporation of the test substance. The animals were immobilized for the 24 hour exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

SCORING SYSTEM: erythema/eschar and edema scoring similar to OECD guideline 404
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact skin, no scoring at 48 h
Remarks:
Study performed according to Appraisal of the safety of chemicals in foods, druge and cosmetics, by the Staft of the Division of Pharmacology, US FDA, skin toxicity according to Draize (1959)
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact skin, no scoring at 48 h
Remarks:
Study performed according to Appraisal of the safety of chemicals in foods, druge and cosmetics, by the Staft of the Division of Pharmacology, US FDA, skin toxicity according to Draize (1959)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other:
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact shaved skin, no scoring at 48 h
Irritant / corrosive response data:
Intact skin:
No irritation was observed on intact skin.

Abraded skin:
1/6 animals showed very slight edema (score 1) after 24 h on abraded skin; this effect was fully reversible within 72 h.
Other effects:
No other effects were reported.
Interpretation of results:
GHS criteria not met
Conclusions:
In this primary dermal irritation study in rabbit, TREGDMA is not a dermal irritant.
Executive summary:

In a primary dermal irritation study similar to US FHSA Federal regulation: 16 CFR 1500.41, 6 rabbits were dermally exposed to 0.5 mL of TREGDMA (according to supplier's information: purity ca. 95%) to approximately 2.5 cm² skin area. Two application sites per animal were treated, one site was left intact, the other was abraded. Test sites were covered with an occlusive dressing for 24 hours. Animals were observed for 72 hours. Irritation was scored similar to FHSA Federal guideline 16 CFR 1500.41. This scoring system is similar to OECD guideline 404.

No dermal irritation response was observed on intact skin. 1/6 animals showed very slight edema (score 1) after 24 h on abraded skin; this effect was fully reversible within 72 h.

In this study, TREGDMA is not a dermal irritant.

Study performance does not comply with requirements of the relevant recent EU and OECD guidelines, where a less vigorous application regime with semi-occlusive dressing, an exposure period of 4 hours, treatment of only intact skin is stipulated.

Thus, it can be assumed, that a substance which shows no irritating activity under the application regime of guideline US FHSA Federal regulation: 16 CFR 1500.41 will also be non irritating under the application regimes of the relevant recent EU and OECD guidelines. Therefore the study is adequate for C&L purposes.

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:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-07-01 to 1997-07-04
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
limited documentation of test data and substance purity
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(1981) and EEC guideline 84/449/EWG, B.4
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
Three healthy adult rabbits of the New Zealand Whte strain were obtained from Harlan Interfauna
(UK) Ltd., Huntingdon, Cambridgeshire, England.
They were in the weight range of 2.4 to 2.6 kg and approximately 10 to 11 weeks of age, prior to
treatment (Day 1). All rabbits were acclimatised to the experimental environrnent.
The rabbits were selected without conscious bias for the study. They were housed individually in meta1
cages with perforated floors in Building R 1 4 Room 5.
A standard laboratory diet SDS Stanrab (P) SQC Rabbit Diet and drinkmg water were provided ad
libitum.
The batch of diet used for the study was analysed for nutrients, contarninants and micro-organisms.
Results of routine physical and chemical examination of drinking water as conducted by the supplier,
are made available to Huntingdon Life Sciences Ltd as quarterly sumrnaries.
Amal room temperature was maintained at 16 to 20°C and relative hurnidity at 52 - 72%. These
environmental pararneters were recorded daily. Air exchange was maintained at approximately 19 air
changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial
light (0700 - 1900 hours) in each 24 hours period.
Each animal was identified by a numbered aluminium tag placed through the edge of one ear. This
nurnber was unique within the Huntingdon Life Sciences Acute Toxicology Departrnent throughout the
duration of the study. Each cage was identified by a coloured labe1 displayng the study schedule
number, animal number and initials of the Study Director and Home Office licensee.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin areas of the test animals serve as the control (clipped).
Amount / concentration applied:
0.5 mL undiluted test substance
Duration of treatment / exposure:
72 hours
Observation period:
Examination of the treated skin was made on Day 1 (ie approximately 60 minutes after removal of the
dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure).
Number of animals:
3
Details on study design:
TREATMENT PROCEDURE
Approximately 24 hours prior to application of the test substance, hair was removed with electric
clippers from the dorso-lumbar region of each rabbit exposing an area of skm approximately 100 mm x100 mm.
Approximately 0.5 ml of the test substance was applied under a 25 mrn x 25 mrn gauze pad to one
intact skin site on each animal.
Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The
animals were not restrained during the exposure period and were retumed to their cages immediately
after treatment.
At the end of the exposure penod, the semi-occlusive dressing and gauze pad were removed and the
treatment site was washed with warm water (30' to 40°C) to remove any residual test substance. The
treated area was blotted dry with absorbent Paper.

OBSERVATIONS
Clinical signs
All animals were observed daily for signs of ill health or toxicity

Dermal responses
Examination of the treated skin was made on Day 1 (ie approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure).


SCORING SYSTEM:
Erythema and Eschar Formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Very severe erythema (beef redness) to eschar formation preventing grading of erythema: 4
Maximum possible: 4

Edema Formation
No edema: 0
Very slight edema (barely perceptible) : 1
Slight edem (edges of area well defined by definite raising):2
Moderate edema (raised approximately 1mm): 3
Severe edema (raised more than 1mm and extending beyond area of exposure):4
Maximum possible: 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Other effects:
not observed

Overall primary irritation score (PDII): 0.0 of 8 scores FDA (Draize), 1959,  re-evaluated according to OECD 404

Reevaluation of the test results according to OECD404/GHS: only records for the shaved skin were considered  Erythema/ 24h     Erythema/72h  Oedema/24h  Oedema/72h
 animal 1  0  0  0  0
 animal 2  0 0  0  0
 animal 3  0  0  0  0
 average (single scores: animal 1 -3)  0.00  0.00  0.00  0.00
 Primary irritation index I = Mean erythema score  (Erythema; 24h, 72h);  out of 4 scores  0.00  Primary irritation index II =  Mean oedema score (Oedema; 24h, 72h);   out of 4 scores  0.00  
 Overall average PDII out of 8 scores; For evaluation according to GHS classification system:  0.00    
Interpretation of results:
GHS criteria not met
Conclusions:
Classification: not irritating
Executive summary:

In a primary dermal irritation study according to OECD TG 404, New Zealand white rabbits were dermally exposed to 0.5 mL Ethylene glycol dimethacrylate (TREGDMA; CAS 109-16-0) for 72 hours. The mean erythema score was determined to be 0.00 out of 4 and, accordingly, the mean edema score 0.00 out of 4. Systemic toxic effects could not be detected as well.The results demonstrate that TREGDMA is not a dermal irritant. Therefore, the test substance has to be classified - according to GHS classification criteria - as non irritant to skin (GHS-hazard category: none).

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:
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:
1994-09-12 to 1994-09-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): BISOMER TEGDMA
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.45 to 2.70 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): rabbit diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 21°C
- Humidity (%): 49 – 69%
- Air changes (per hr): app. 15/h
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated contralateral eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
eyes were not rinsed after application
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize scale, OECD guideline 405

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
- in 1/3 animals grade 1 redness (vessels definitily injected above normal) was observed 1 h after application; 2/3 animals showed no irritating effects at 1 h after treatment
- all eyes appeared normal at the 24, 48 and 72 h observations
Other effects:
no other effects reported
Interpretation of results:
not irritating
Conclusions:
TREGDMA is not irritating to the rabbit eye.
Executive summary:

In a primary eye irritation study according to OECD guideline 405, adopted 24 February 1987, and EU method B.5, 0.1 mL of TREGDMA (purity ca. 95% according to supplier) was instilled into the conjunctival sac of 3 young adult New Zealand White rabbits (1 male, 2 females) without washing. Animals then were observed for 3 days.  Irritation was scored by the method of Draize. 

No effects were observed in cornea and iris. Only minimal (grade 1) redness was observed in 1/3 animals 1 h after treatment. All eyes appeared normal at the 24, 48 and 72 h observations.

In this study, TREGDMA is not irritating to the rabbit eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Reliable (RL=1-2),relevant and adequate data are available for the skin and eye irritation potential of TREGDMA.

 

Skin irritation

In a primary dermal irritation study similar to US FHSA Federal regulation: 16 CFR 1500.41, 6 rabbits were dermally exposed to 0.5 mL of TREGDMA (according to supplier's information: purity ca. 95%) to approximately 2.5 cm² skin area. Two application sites per animal were treated, one site was left intact, the other was abraded. Test sites were covered with an occlusive dressing for 24 hours. Animals were observed for 72 hours. Irritation was scored similar to FHSA Federal guideline 16 CFR 1500.41. This scoring system is similar to OECD guideline 404.

No dermal irritation response was observed on intact skin. 1/6 animals showed very slight edema (score 1) after 24 h on abraded skin; this effect was fully reversible within 72 h. In this study, TREGDMA is not a dermal irritant.

Study performance does not comply with requirements of the relevant recent EU and OECD guidelines, where a less vigorous application regime with semi-occlusive dressing, an exposure period of 4 hours, treatment of only intact skin is stipulated. Thus, it can be assumed, that a substance which shows no irritating activity under the application regime of guideline US FHSA Federal regulation: 16 CFR 1500.41 will also be non irritating under the application regimes of the relevant recent EU and OECD guidelines. Therefore the study is adequate for C&L purposes.

 

In a dermal irritation study in humans, 10 test persons were exposed to TREGDMA in concentrations of 1% and 3% in olive oil for 48 h using the Roc Neodermotest. No skin irritation was observed after 48 h. In this study under the conditions reported, TREGDMA is not a dermal irritant.

In a primary dermal irritation study according to the method of Draize rabbits were dermally exposed to TREGDMA in olive oil at concentrations of 10%, 50% and 100%. Primary dermal irritation indices (PDII) were 0.1, 1.6 and 2.7 – 3.4 for the 10, 50 and 100% groups, respectively.

In this study, TREGDMA is not a dermal irritant. 

 

Eye irritation

In a primary eye irritation study according to OECD guideline 405, adopted 24 February 1987, and EU method B.5, 0.1 mL of TREGDMA (purity ca. 95% according to supplier) was instilled into the conjunctival sac of 3 young adult New Zealand White rabbits (1 male, 2 females) without washing. Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

No effects were observed in cornea and iris. Only minimal (grade 1) redness was observed in 1/3 animals 1 h after treatment. All eyes appeared normal at the 24, 48 and 72 h observations.

In this study, TREGDMA is not irritating to the rabbit eye.

 

Respiratory irritation

No data on the respiratory irritation of TREGDMA are available. 

 

There are no data gaps for the endpoint irritation/corrosion. No human information is available skin irritation with the undiluted test substance and for eye irritation. However, there is no reason to believe that the available results would not be applicable to humans.


Compliance to REACh requirements

The requirements are covered with reliable in vivo data, performed with the substance itself and before in vitro testing became current priority.

Justification for classification or non-classification

Based on the available data, TREGDMA does not need to be classified for eye irritation or skin irritation according to regulation (EC) 1272/2008 . Thus, no labelling is required.