Registration Dossier

Administrative data

Description of key information

Skin:


Skin irritation, Rabbit, 4h, OECD 404: No reactions observed (Cytec, Huntingdon Research Centre, 1986)


Skin irritation, Rabbit, 4h, OECD 404: No reactions observed (BASF, 1991)


Skin irritation, Rabbit, 4h, OECD 404: Slight to moderate erythema (0.3), no edema (BASF, 2002)


Skin irritation, Rabbit, 4h, OECD 404: No reactions observed (Cray Valley, Huntingdon, 1994)


 


Eye:


Eye irritation,  Rabbit, OECD 405: Slight to severe signs (cornea opacity 1.0, iris lesion 0.7, redness of conjunctiva 2.6 and chemosis 2.1). Fully reversible within 14 days. (BASF, 2002)


Eye irritation, Rabbit, OECD 405: Slight to well defined signs (cornea opacity 1.0, iris lesion 0.4, redness of conjunctiva 2.3 and chemosis 1.6). Irritation effect still appears in one animal after 23d, expected to be residual finding. (BASF, 1991)


Eye irritation,  Rabbit, EPA TSCA: Slight to severe signs (cornea opacity 1.0, iris lesion 1, redness of conjunctiva 1.9 and chemosis 2.0). Fully reversible within 10 days (Cognis, Food & Drug Research Laboratories, 1984).


Eye irritation, Rabbit, OECD 405: Slight to moderate signs (cornea opacity 0.33, iris lesion 0.11, redness of conjunctiva 1.22 and chemosis 0.56). Fully reversible within 7 days (Rahn, RCC Ltd., 1999)


Eye irritation, Rabbit, EU Method B.5: slight to severe signs (cornea opacity 1.11, iris lesion 0.33, redness of conjunctiva 2.56 and chemosis 2.44). Fully reversible within 14 days, but one animal was killed on human grounds on day 4 (Cytec, Huntingdon, 1993).

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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Weight at study initiation: mean weight male animals: 2.78 kg, weight female animal: 2.66 kg
- Housing: individually in cages made of stainless steel with wire mesh walk floors. Floor area: 40x51 cm
- Diet: about 130 g per animal per day
- Water: about 250 ml per animal per day
- Acclimation period: at least 8 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12h/12h
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites of the same animal
Amount / concentration applied:
undiluted, 0.5 ml of the test substance were applied
Duration of treatment / exposure:
4 hour(s)
Observation period:
as no findings were observed, the animals were only observed for 3 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: test patches were secured in position with a porous dressing (four layers of absorbent gauze + poous bandage)


REMOVAL OF TEST SUBSTANCE
- Washing: at the end of the exposure period with lutrol and lutrol/water (1:1)
- Time after start of exposure: 4 h
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable

The mean scores of all animals for edema and erythema was 0 for 24, 48 and 72 hours. The substance is therefore not irritating according to EU- and GHS-criteria.

Interpretation of results:
GHS criteria not met
Remarks:
not irritating
Conclusions:
The substance showed no signs of irritation and therefore has to be classified as not irritating to the skin.
Executive summary:

A study according to OECD 404 was performed assessing the skin irritation potential of TMPeoTA (BASF, 1991, Dr. Kirsch). Therefore 3 Vienna White rabbits received 0.5ml undiluted TMPeoTA to skin. Gradings were recorded 30-60, 24h, 48h, 72h after the end of the 4h semi occlusive covered exposure period. The mean scores of all animals for edema and erythema was 0 for 24, 48 and 72 hours. In result the TMPeoTA shows no signs of skin irritation.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study not according to OECD guideline and with acceptable limitations
Qualifier:
according to guideline
Guideline:
other: Code of Federal regulations, Title 16, Section 1500.41
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: 10 to 13 weeks of age
- Weight at study initiation: 2.3 to 3.0 kg
- Housing: individually in plastic cages with perforated floors
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: all animals were acclimatised to the experimental environment


ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 19 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12h/12h
Type of coverage:
occlusive
Preparation of test site:
other: one test with intact skin, one with abraded skin
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
3 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 25 mm x 25 mm
- Type of wrap if used: The treatment sites were covered with "Elastoplast" elastic adhesive dressing backed with "Sleek" waterproof strapping.


REMOVAL OF TEST SUBSTANCE
- Washing: washed with warm water (30 ° to 40° C), the treated areas were blotted dry with absorbent paper
- Time after start of exposure: 24 hours


SCORING SYSTEM:

Local dermal irritation was assessed using the prescribed numerical system :

Erythema and eschar formation:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema formation :
No oedema: 0
Very slight oedema (bazely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 millimetre): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
mean
Time point:
other: 24/72 hours
Score:
0.5
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
mean
Time point:
other: 24/72 hours
Score:
0
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
mean
Time point:
other: 24/72 hours
Score:
0.42
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
mean
Time point:
other: 24/72 hours
Score:
0
Irritation parameter:
primary dermal irritation index (PDII)
Score:
0.5
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period .

The mean value (24 and 72 h) of the scores of either erythema and eschar formation or edema formation in this test was calculated over all animals tested or for each animal individually. As the mean scores for erythema and oedema formation were below 2

with intact skin as well as with abraded skin in all animals and for each individual animal, the substance was considered as not irritating to the skin.

Interpretation of results:
GHS criteria not met
Remarks:
not irritating
Conclusions:
TMPeoTA was found to be mildly irritating according to Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, (1959).
Executive summary:

This study was performed to assess the skin irritation potential of TMPeoTA to the rabbit . The method followed was that described in Code of Federal Regulations, Title 16, Section 1500 .41 . Six rabbits were each administered a dermal dose of 0.5 ml of the test substance to one intact and one abraded skin site and observed for three days . A single occlusive application of TMPeoTA to intact and abraded rabbit skin for twenty-four hours elicited very slight dermal irritation . The Primary Irritation Index (PII) was calculated to be 0.5

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment
Qualifier:
according to guideline
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.41
Principles of method if other than guideline:
Six rabbits were exposed to the test substance (0.5 ml) for 24 hours under occlusive conditions. The animals were observed for 72 hours and readings were performed after 24 and 72 hours.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., England
- Age at study initiation: 11-13 weeks of age
- Weight at study initiation: 2.4-2.9 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: yes, length not specified


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 19 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 2.5 cm x 2.5 cm
- Type of wrap if used: "Elastoplast" elastic adhesive dressing backed with "Sleek" waterproof strapping


REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water
- Time after start of exposure: 24 hours


SCORING SYSTEM: equivalent to the scoring system described in OECD 404 guideline
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24/72 hours
Score:
0.08
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24/72 hours
Score:
0
Reversibility:
other: all animals were free of signs of edema at all times

Individual mean (24/72 hours) score of the animals:

erythema: 0 in 5/6 animals; 0.5 in 1/6 animals

edema: 0 in 6/6 animals

the scores made with abraded skin were not taken into account.

As signs of irritation were almost absent, the test substance is not irritating to the skin according to EU- and GHS-criteria.

Interpretation of results:
GHS criteria not met
Remarks:
not irritating
Conclusions:
A single occlusive application of twat substance to intact and abraded rabbit skin for twenty-four hours elicited very slight dermal irritation
Executive summary:

A study was performed to assess die skin irritation potential of test substance to the rabbit. The method followed was that described in Code of Federal Regulations, Title 16, Section 1500.41. Six rabbits were each administered a dermal dose of 0.5 ml of die test substance to one intact and one abraded skin site and observed for three days. A single occlusive application of "confidential substance name" to intact and abraded rabbit skin for twenty-four hours elicited very slight dermal irritation. The Primary Irritation Index (PII; calculated according to CFR) was calculated to be 0.2.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S.A., France
- Age at study initiation: 8-9 months
- Weight at study initiation: 3.95-4.00 kg
- Housing: individually
- Diet: 130g/animal/day (Kliba-Labordiät)
- Water: ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
72 hours as all animals were free of signs of irritation
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsolateral part of the trunk
- % coverage: 2.5 cm x 2.5 cm
- Type of wrap if used: test patch and Fixomull stretch


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with Lutrol and Lutrol/water (1:1)
- Time after start of exposure: 4 hours


SCORING SYSTEM: according to OECD guideline 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: animals were free of signs of edema at all times

The mean individual scores (24/48/72 hours) of the animals were:

erythema: 0 in 2/3 animals, 1 in 1/3 animals

edema: 0 in 3/3 animals

The test substance is not irritating to the skin according to EU- and GHS-criteria as only marginal signs of irritation were observed in one animal.

Interpretation of results:
GHS criteria not met
Remarks:
not irritating
Conclusions:
TMPeoTA does not give indication of an irritant property to the skin under the test conditions chosen
Executive summary:

The potential of "confidential substance name" to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml of the test substance to the intact skin of 3 White New Zealand rabbits for 4 hours under semiocclusive dressing.

After removal of the patch the application area was washed off. The cutaneous reactions were assessed approximately 1, 24, 48 and 72 hours after removal of the patch.

Slight or moderate erythema was observed in all animals during the course of the study. The cutaneous reactions were reversible in all animals within 72 hours after removal of the patch at latest. The average score (24 to 72 hours) for irritation was calculated to be 0.3 for erythema and 0.0 for edema.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to CFR guideline conducted under GLP
Qualifier:
according to guideline
Guideline:
other: CFR 1500.41
Principles of method if other than guideline:
The study was conducted in accordance with the Federal Hazardous Substance Act Regulations (16 CFR Part 1500).
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5ml
Duration of treatment / exposure:
24h
Observation period:
24.5h; 72h
Number of animals:
6
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24.5h; 72h
Score:
4.42
Max. score:
8
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
mean
Time point:
other: mean of 24.5h and 72h
Score:
1.91
Max. score:
4
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: mean of 24.5 and 72h
Score:
1.91
Max. score:
4
Reversibility:
no data
Irritant / corrosive response data:
no corrosive effects reported
Interpretation of results:
GHS criteria not met
Conclusions:
Test article application caused dermal irritation characterized by very slight to moderate-severe erythema and very slight to severe edema.
Executive summary:

Test substance was evaluated for potential primary dermal irritation using six New Zealand White rabbits. Each rabbit was administered 0.5 ml of the test article to one intact and one abraded test site. The test sites were occluded for 24 hours following dose application. Dermal irritation was scored according to the Draize method at 24.5 and 72 hours after test article application. Test article application caused dermal irritation characterized by very slight to moderate-severe erythema and very slight to severe edema. The mean primary dermal irritation score was calculated to be 4.42. Under the conditions of this study and as outlined in 16 CFR Part 1500, where a mean score of 5 or greater is indicative of a skin irritant, test substance is not considered a primary skin irritant.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
13 September 1994 to 16 September 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 404 with minor deviations: no certificate of analysis, no data on the purity of the test substance and accomodation period of the animals
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
no certificate of analysis, no data on the purity of the test substance and accomodation period of the animals
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
no certificate of analysis, no data on the purity of the test substance and accomodation period of the animals
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, England
- Age at study initiation: 11-13 weeks
- Weight at study initiation: 2.5-3.1 kg
- Housing: individually in plastic cages with perforated floors
- Diet (e.g. ad libitum): SDS Stanrab (P) Rabbit Diet, ad libitum
- Water (e.g. ad libitum): standard laboratory water, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19
- Humidity (%): 30-70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 September 1994 To: 16 September 1994
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
3 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 25 x 25 mm
- Type of wrap if used: 25 mm x 25 mm gauze pad covered with "Elastoplast" elastic adhesive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water (30 to 40°C) and blotted dry with absorbent paper
- Time after start of exposure: 4 h

SCORING SYSTEM:

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation
(injuries in depth) preventing erythema reading 4

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema
(edges of area well-defined by definite raising) 2
Moderate oedema
(raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre
and extending beyond the area of exposure) 4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No dermal response to treatment was observed in any of the animals throughout the observation period.
Other effects:
No data

No data

Interpretation of results:
GHS criteria not met
Remarks:
not irritating
Conclusions:
Under the test conditions, TMPeoTA is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).
Executive summary:

In a dermal irritation GLP study performed according to OECD guideline 404, three young adult female White New-Zealand rabbits were dermally exposed to 0.5 mL of TMPeoTA for 4 hours to 6.25 cm² of clipped skin. Animals then were observed for 3 days.

There was no irritant effect at any observation time point, all scores for any animals were 0. In this study, TMPeoTA is not a dermal irritant on female rabbits. Under the test conditions, TMPeoTA is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From January 31, 1984 to April 11, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles, acceptable for assessment.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Principles of method if other than guideline:
Primary skin irritation study was performed in rabbits. Test material was applied to the abraded skin of rabbits and scores were recorded after 72 h according to Draize system.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
IN-LIFE DATES: From: 1984-01-23 to: 1984-03-02
Type of coverage:
not specified
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
No data
Observation period:
72 h
Number of animals:
Four (3 males and 1 female)
Details on study design:
SCORING SYSTEM: Standard Draize scoring system (0-4) followed for erythema/eschar formation and edema formation
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
1.75
Max. score:
4
Reversibility:
no data
Remarks on result:
other: -
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
0.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: -
Irritant / corrosive response data:
- Well defined erythema, generally with very slight edema in 3 animals
- Very slight erythema in one animal
Other effects:
No data

Table 1. Dermal irritation observations (Right front)

After 72 h (1 site/animal)

ER

2

2

2

1

ED

0

1

1

0

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
The mean skin irritation index of TMPeoTA was 2.25 and was considered to be mildly irritating to rabbit skin.
Executive summary:

A study was conducted to evaluate the skin irritation of TMPeoTA in rabbits. Therefore 0.5 mL of undiluted TMPeoTA was applied to the abraded skin of 3 male rabbits and 1 female rabbit. Skin reactions were scored according to the standard Draize system after 72 h of application.

Three animals had well defined erythema, generally with very slight edema. One animal had very slight erythema. At 72 h, mean erythema and edema scores were calculated to be 1.75 and 0.5 respectively. The combined index was calculated to be 2.25. In conclusion, TMPeoTA an be considered as mild irritant to rabbit skin.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Adequate conducted study according to OECD guideline and with quality assurance
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
4h
Observation period:
30min, 24h, 48h, 72h
Number of animals:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h
Score:
0
Max. score:
4
Irritant / corrosive response data:
no corrosive effects reported
Interpretation of results:
GHS criteria not met
Remarks:
not irritating
Conclusions:
A single semi-occlusive application of teswt substance to intact rabbit skin for four hours elicited no dermal irritation.
Executive summary:

A skin irritation test according to OECD 404 was determined to evaluate the irritative potential to skin of test substance.

Therefore 3 new zealand white rabbits where exposed for 4h to 0.5ml undiluted test material. Gradings were examined at 30min, 24h, 48h and 72h.None of the animals showed any observable response to treatment throughout the four days observation period.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to GLP and OECD guideline
Qualifier:
according to guideline
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.41
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: mean of 24h and 72h
Score:
0.04
Max. score:
8
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: mean of 24h and 72
Score:
0.08
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: mean of 24h and 72
Score:
0
Max. score:
4
Irritant / corrosive response data:
no corrosive effects reported

Only one animal showed slight erythema in 24h reading. All other animals were treatment related effect free.

Interpretation of results:
GHS criteria not met
Remarks:
not irritating
Conclusions:
A single occlusive application of TMPeoTA to intact and abraded rabbit skin for twenty-four hours elicited a very slight dermal reaction and is classified as mildly irritating.
Executive summary:

A study was performed to assess the skin irritation potential of TMPeoTA to the rabbit skin. The method followed was that described in Code of Federal Regulations, Title 16, Section 1500.41. Six rabbits were each administered a dermal dose of 0.5 ml of the test substance to one intact and one abraded skin site and observed for three days. A single occlusive application of

TMPeoTA

to intact and abraded rabbit skin for twenty-four hours elicited a very slight dermal reaction. The Primary Irritation Index (PII) was calculated to be 0.04.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Weight at study initiation: mean weight male animals: 3.35 kg, weight female animal: 3.15 kg
- Housing: individually in cages made of stainless steel with wire mesh walk floors. Floor area: 40x51 cm
- Diet: about 130 g per animal per day
- Water: about 250 ml per animal per day
- Acclimation period: at least 8 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12h/12h
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml
Duration of treatment / exposure:
single application to the conjunctival sac of the right eyelid; the substance was not washed out
Observation period (in vivo):
23 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- the substance was not washed out
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24/48/72 hours
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 23 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24/48/72 hours
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 17 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24/48/72 hours
Score:
2.67
Max. score:
3
Reversibility:
not fully reversible within: 23 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24/48/72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 23 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24/48/72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 17 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24/48/72 hours
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24/48/72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24/48/72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24/48/72 hours
Score:
0.67
Max. score:
2
Reversibility:
fully reversible
Remarks:
8 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24/48/72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24/48/72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 days

Table 1: Results of acute eye irritation:

Readings

Animal

Cornea

Iris

Conjunctiva redness

Conjunctiva chemosis

Symptoms

1 h

1

0

0

2

0

 

2

0

0

2

0

 

3

0

0

2

0

 

24 h

1

1

0

2

2

DB/S/PC

2

1

0

3

2

S

3

1

0

2

2

S

48 h

1

1

1

3

3

PC/S/RE/MV

2

1

0

2

1

PC/S

3

1

1

2

1

S

72 h

1

1

1

3

1

PC/S/RE/MV

2

1

0

2

1

PC/RE

3

1

1

2

1

LC

8 d

1

1

1

2

1

PC/S/RE/LC

2

1

0

1

0

LC

3

0

0

0

0

 

17 d

1

1

0

2

1

PC/S/RE/LC/MV

2

0

0

0

0

 

3

0

0

0

0

 

23 d

1

1

0

1

0

PC/MV/LC/RE

2

0

0

0

0

 

3

0

0

0

0

 

DB - DISCHARGE OF BLOOD; LC - LOSS OF CORNEAL TISSUE; MV - MARGINAL VASCULARIZATION OF THE CORNEA; PC - PUPIL CONTRACTED; RE - SMALL RETRACTIONS IN THE EVELIDS; S - SUPPURATION

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Slight opacity and iritis as well as well-defined conjunctivia redness and chemosis points to eye irritating potential. The irritative effect still appears in one animal after 23d.
Executive summary:

The eye irritation of "confidential substance name" was investigated according OECD 405 guideline. Therefore 0.1ml of the test substance was instilled into the eye of 3 rabbits (vienna white). No washout was performed and gradings were recorded after 1h, 24h, 48h, 72h, 8d, 17d and 23d. The untreated eye serves as negative control.

Slight opacity (1 (max 4)) and iris leasions (0.4 (max 2) as well as well-defined conjunctivia redness (2.3 (max 3)) and chemosis ( 1.6 (max 4)) were calculated as mean of 24h, 48h and 72h reading.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S.A., France
- Age at study initiation: 3-4 months
- Weight at study initiation: 2.65-2.80 kg
- Housing: individually
- Diet: ca. 130 g/animal/day (Kliba-Labordiät)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
single application; substance was washed out after 24 hours
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 24 hours

SCORING SYSTEM: according to OECD guideline 405

TOOL USED TO ASSESS SCORE: light
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.56
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
2.11
Max. score:
4
Reversibility:
fully reversible within: 7 days

The mean individual scores of the animals (24/48/72 hours) were:

corneal opacity: 1 in 3/3 animals

iris: 0 in 1/3 animals, 0.67 in 1/3 animals and 1.33 in 1/3 animals

redness of the conjunctivae: 2.33 in 1/3 animals; 2.67 in 2/3 animals

chemosis: 1.67 in 1/3 animals, 2.33 in 2/3 animals

Due to the overall and individual mean scores observed, the test substance has to be classified as irritating to eye (R36) according to EU- and as eye irritant Cat. 2A according to GHS-criteria.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Indication of an irritant property to the eye
Executive summary:

The potential of "confidential substance name" to cause damage to the conjunctiva, Iris or cornea was assessed in 3 White New Zealand rabbits, subjected to a single ocular application of 0.1 ml of the test substance according to OECD 405.

The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and then in weekly intervals until day 14.

Slight to severe conjunctival redness, slight to marked conjunctival swelling and slight to severe discharge were observed during the course of the study. Slight corneal opacity was observed in all animals and moderate or severe iritis was noted in two animals during the observation period.

The ocular reactions were reversible in all animals within 14 days after application. The average score (24 to 72 hours) for irritation was calculated to be 1.0 for corneal opacity, 0.7 for iris, 2.6 for conjunctival redness and 2.1 for chemosis.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically well documented study under GLP
Qualifier:
according to guideline
Guideline:
other: EPA TSCA
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: one eye per animal stays untreated
Amount / concentration applied:
0.1ml
Duration of treatment / exposure:
two experiment one with 30 sec wash out and one without wash out
Observation period (in vivo):
1h; 24h; 48h; 72h; daily during day 7 and
every 3 days until day 21
Number of animals or in vitro replicates:
6 (without washout)
Irritation parameter:
cornea opacity score
Remarks:
(without washout)
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h reading
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Remarks:
(without washout)
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h reading
Score:
1
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness (without washout)
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h reading
Score:
1.9
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Remarks:
(without washout)
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h reading
Score:
2
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
no corrosive effects reported
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Mildly to moderate irritating effect were observed
Executive summary:

To investigated the eye irritating potential of "confidential substance name" an eye irritation study was performed according to the rules of EPA TSCA und GLP. Therefore 0.1ml test substance was instilled in one eye of 6 rabbits (New Zealand White). A second experiment was conducted where the eyes of 3 rabbits were washed after 30 sec of test item instillation. (Data not shown here)

Gradings of irritation were recorded after  1h; 24h; 48h; 72h; daily during day 7 and every 3 days until day 21 if the effect is already there.

Mildly to moderate irritating effect were observed (opacity 1 (max 4); irritis 1 (max 2); conjunctivia rednesss 1.9 (max 3) and chemosis 2 (max 4))

The test is conducted according to EPA TSCA specification therefore some specification maybe not compareable to OECD guideline. If GHS EU rules are applied the substance would be classified as irritating to eye cat 2.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From January 23, 1984 to April 11, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Reason / purpose for cross-reference:
reference to other study
Principles of method if other than guideline:
A study was conducted to evaluate the ocular toxicity of the test material in rabbits. 0.1 mL of the test material was instilled into the right eye of four rabbits; the left eye served as an untreated control. Irritation was scored by Draize scoring system at 0 h, 24 h and Day 7 post-instillation.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
IN-LIFE DATES: From: 1984-01-23 to: 1984-07-03
Vehicle:
unchanged (no vehicle)
Controls:
other: Left eye served as untreated control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100 %


Duration of treatment / exposure:
Single treatment without eye wash
Observation period (in vivo):
0 h, 24 h and Day 7
Number of animals or in vitro replicates:
Four
Details on study design:
SCORING SYSTEM: Draize method (Draize, 1969)


TOOL USED TO ASSESS SCORE: Fluorescein
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Redness
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24 h
Score:
0
Max. score:
2
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: Redness
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24 h
Score:
0
Max. score:
2
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 h
Score:
> 0 - < 1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Slight dulling of normal luster
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24 h
Score:
> 0 - < 1
Max. score:
2
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Slight deepening of the rugae or slight hyperemia of the circumcorneal blood vessels
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: 24 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #4
Time point:
other: 24 h
Score:
> 0 - < 1
Max. score:
2
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Slight deepening of the rugae or slight hyperemia of the circumcorneal blood vessels
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
other: 24 h
Score:
> 0 - < 1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Slight dulling of normal luster
Irritant / corrosive response data:
At 24 h, all the animals had conjunctival irritation, one had corneal opacity, two had corneal ulceration and two had minor corneal changes. All animals were free of significant irritation at Day 7, although two continued to exhibit slight conjunctival redness and/or corneal dullness.
Other effects:
None

None

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Test substance was irritating to rabbit eyes. At 24 h, all the animals exposed to the test substance had conjunctival irritation, one had corneal opacity, two had corneal ulceration and two had minor corneal changes. All animals were free of significant irritation at Day 7, although two continued to exhibit slight conjunctival redness and/or corneal dullness.
Executive summary:

A study was conducted to evaluate the ocular toxicity of C-661in rabbits.

0.1 mL of C-661 was instilled into the right eye of four rabbits; the left eye served as an untreated control. Irritation was scored by Draize scoring system at 0 h, 24 h and Day 7 post-instillation.

 

At 24 h, all the animals exposed to C-661 had conjunctival irritation, one had corneal opacity, two had corneal ulceration and two had minor corneal changes. All animals were free of significant irritation at Day 7, although two continued to exhibit slight conjunctival redness and/or corneal dullness.

In conclusion, C-661 was irritating to rabbit eyes.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
June 21, 1993 to July 12, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study is according to EU Method B.5 (Acute toxicity: Eye irritation/corrosion).
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: 12 - 15 weeks
- Weight at study initiation: 2.8 - 3.4 kg
- Housing: Individually in metal cages with perforated floors
- Diet (e.g. ad libitum): SDS Stanrab (P) Rabbit Diet, ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature: 19 °C
- Humidity: 30 - 70%
- Air changes: 19 per h
- Photoperiod: 12 h dark / h light

Vehicle:
unchanged (no vehicle)
Controls:
other: Contralateral eye served as untreated control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:
Single treatment
Observation period (in vivo):
Clinical signs: All animals were observed daily for signs of ill health or toxicity.
Ocular responses: 14 d; eye irritation scored after 1 h of instillation and on Day 1, 2, 3, 4, 7 and 14.
Number of animals or in vitro replicates:
Three
Details on study design:
SCORING SYSTEM: According to EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion).


Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 14 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1.67
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0.67
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
2.67
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
3
Max. score:
4
Irritant / corrosive response data:
Corneal opacification (diffuse or easily discernible) was recorded between one and seven days after instillation of the test material, and was accompanied by swelling of the cornea for one animal. Iridial inflammation was recorded for all three animals, lasting up to four days after instillation. The
response was severe for one animal. Diffuse, crimson colouration of the conjunctivae was recorded for all three animals 1 h following instillation of the test material. This progressed to diffuse beefy red for all animals and was accompanied by obvious swelling of the lids. The swelling was with the lids about half-closed for one animal and with the lids more than half-closed for one other animal. The eyes of surviving animals were normal 7 or 14 d after instillation.
Other effects:
One animal was killed on humane grounds four days after instillation of the test material. The animal was showing a pain response as a result of severe eye reactions caused by instillation of the test material. There were no other signs of toxicity or ill health in any rabbit during the observation period.

None

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Eb 160 (Liquid polyol acrylate) was considered to be irritating to rabbit eyes.
Executive summary:

A study was conducted to evaluate the ocular toxicity of TMPeoTA (Liquid polyol acrylate) in rabbits. The study was performed according to the EU Method B.5 (Acute toxicity: Eye irritation/corrosion). 0.1 mL of the test substance was instilled into the eye of three New Zealand White rabbits; the contralateral eye served as an untreated control. One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed (pilot animal). Irritation was scored after 1 h of instillation and on Day 1, 2, 3, 4, 7 and 14.

Corneal opacification (diffuse or easily discernible) was recorded between one and seven days after instillation of the test substance, and was accompanied by swelling of the cornea for one animal. Iridial inflammation was recorded for all three animals, lasting up to four days after instillation. The response was severe for one animal. Diffuse, crimson colouration of the conjunctivae was recorded for all three animals 1 h following instillation of the test material. This progressed to diffuse beefy red for all animals and was accompanied by obvious swelling of the lids. The swelling was with the lids about half-closed for one animal and with the lids more than half-closed for one other animal. Mean scores are as follows: cornea score 1.11, iris score 0.33, redness 2.56 and chemosis 2.44.The eyes of surviving animals were normal 7 or 14 days after instillation. One animal was killed on humane grounds four days after instillation of the test material. The animal was showing a pain response as a result of severe eye reactions caused by instillation of the test material. There were no other signs of toxicity or ill health in any rabbit during the observation period. In conclusion, TMPeoTA was considered to be irritating to rabbit eyes.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted and documented study according to OECD and GLP guidelines
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: one eye per animal stays untreated
Amount / concentration applied:
0.1ml
Duration of treatment / exposure:
no washout
Observation period (in vivo):
1, 24, 48 and 72 hours, as well as 7 days after administration
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean of 24, 48 and 72h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of 24, 48 and 72h
Score:
0.11
Max. score:
2
Reversibility:
fully reversible within: 48h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: mean of 24, 48 and 72h
Score:
1.22
Max. score:
3
Reversibility:
fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean of 24, 48 and 72h
Score:
0.56
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritant / corrosive response data:
No corrosion was observed at any of the measuring intervals.
Interpretation of results:
not irritating
Conclusions:
The test substance is considered to be "not irritating" to the rabbit eye
Executive summary:

The primary irritation potential of the test article was investigated by instillation of 0.1 ml into one eye of each of three young adult New Zealand White rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7 days after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion.

Slight opacity was observed in all animals 48 hours after administration. Slightly to moderately reddened conjunctivae was observed in all animals from the 1- to the 72-hour reading as well as swollen nictitating membrane and/or slight swelling of the eyelids in both females from the 24- to the 48- or 72-hour reading. Slight to moderate watery discharge was observed in the females between the 1- and 72-hour reading. Mean scores are as follows: cornea score 0.33, iris score 0.11, redness 1.22 and chemosis 0.56. All eye reactions were clear within 7 days after treatment.

According to GHS EU rules the substance has not to be classified as irritating to eye.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are valid in vivo study data available assessing the irritating potential of ethoxylated trimethylolpropane triacrylate (TMPeoTA) to skin and eye.


 


Skin irritation:


Long-time application studies (24h, CFR etc):


Ethoxylated trimethylolpropane triacrylate (TMPeoTA) was evaluated for potential primary dermal irritation using six New Zealand White rabbits conducted in accordance with the Federal Hazardous Substance Act Regulations (16 CFR Part 1500) (Cognis, Food & Drug Research Laboratories, 1990). Each rabbit was administered 0.5 ml of the test article to one intact and one abraded test site. The test sites were occluded for 24 hours following dose application. Dermal irritation was scored according to the Draize method at 24.5 and 72 hours after test article application. Test article application caused dermal irritation characterized by very slight to moderate-severe erythema and very slight to severe edema. The mean primary dermal irritation score was calculated to be 4.42. Under the conditions of this study and as outlined in 16 CFR Part 1500, where a mean score of 5 or greater is indicative of a skin irritant, TMPeoTA is not considered a primary skin irritant.


Another study was performed to assess the skin irritation potential of TMPeoTA to the rabbit skin (Rahn, Huntingdon Research Centre, 1995). The method followed was that described in Code of Federal Regulations, Title 16, Section 1500.41. Six rabbits were each administered a dermal dose of 0.5 ml of the test substance to one intact and one abraded skin site and observed for three days. A single occlusive application of TMPeoTA to intact and abraded rabbit skin for twenty-four hours elicited a very slight dermal reaction. The Primary Irritation Index (PII) was calculated to be 0.04.


A further study was performed to assess the skin irritation potential of TMPeoTA to the rabbit (BASF, Huntingdon, 1997). The method followed was that described in Code of Federal Regulations, Title 16, Section 1500 .41. Six rabbits were each administered a dermal dose of 0.5 ml of the test substance to one intact and one abraded skin site and observed for three days. A single occlusive application of TMPeoTA to intact and abraded rabbit skin for twenty-four hours elicited very slight dermal irritation. The Primary Irritation Index (PII) was calculated to be 0.5


Another study was performed to assess die skin irritation potential of TMPeoTA to the rabbit (BASF, Huntingdon, 1997). The method followed was that described in Code of Federal Regulations, Title 16, Section 1500.41. Six rabbits were each administered a dermal dose of 0.5 ml of die test substance to one intact and one abraded skin site and observed for three days. A single occlusive application of the test substance to intact and abraded rabbit skin for twenty-four hours elicited very slight dermal irritation. The Primary Irritation Index (PII; calculated according to CFR) was calculated to be 0.2.


 


 OECD 404 / EEC B.4 conform studies:


 A skin irritation test according to OECD 404 was determined to evaluate the irritative potential to skin of TMPeoTA (Cytec, Huntingdon Research Centre, 1986). Therefore 3white rabbits where exposed for 4h to 0.5ml undiluted test material. Gradings were examined at 30min, 24h, 48h and 72h. None of the animals showed any observable response to treatment throughout the four days observation period.


Another study according to OECD 404 was performed assessing the skin irritation potential of TMPeoTA (BASF, 1991). Therefore 3 Vienna White rabbits received 0.5ml undiluted TMPeoTA to skin. Gradings were recorded 30-60, 24h, 48h, 72h after the end of the 4h semi occlusive covered exposure period. The mean scores of all animals for edema and erythema was 0 for 24, 48 and 72 hours. In result the TMPeoTA shows no signs of skin irritation.


In a further study the potential of TMPeoTA to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml of the test substance to the intact skin of 3 White New Zealand rabbits for 4 hours under semi occlusive dressing (BASF, 2002). After removal of the patch the application area was washed off. The cutaneous reactions were assessed approximately 1, 24, 48 and 72 hours after removal of the patch. Slight or moderate erythema was observed in all animals during the course of the study. The cutaneous reactions were reversible in all animals within 72 hours after removal of the patch at latest. The average score (24 to 72 hours) for irritation was calculated to be 0.3 for erythema and 0.0 for edema. In result TMPeoTA does not give indication of an irritant property to the skin under the test conditions chosen.


In a further dermal irritation GLP study performed according to OECD guideline 404, three young adult female White New-Zealand rabbits were dermal exposed to 0.5 mL of TMPeoTA for 4 hours to 6.25 cm² of clipped skin (Cray Valley, Huntingdon, 1994). Animals then were observed for 3 days. There was no irritant effect at any observation time point, all scores for any animals were 0. In this study, TMPeoTA is not a dermal irritant on female rabbits. Under the test conditions, TMPeoTA is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).


 


Studies according to other protocols:


A study was conducted to evaluate the skin irritation of TMPeoTA in rabbits (Cytec, Bio/Dynamics, 1984). Therefore 0.5 mL of undiluted TMPeoTA was applied to the abraded skin of 3 male rabbits and 1 female rabbit. Skin reactions were scored according to the standard Draize system after 72 h of application. Three animals had well defined erythema, generally with very slight edema. One animal had very slight erythema. At 72 h, mean erythema and edema scores were calculated to be 1.75 and 0.5 respectively. The combined index was calculated to be 2.25. In conclusion, TMPeoTA is considered as mild irritant to rabbit skin.


 


Assessment skin irritation:


All available information is taken into account to assess the skin irritating potential of TMPeoTA. An increased dermal reaction can be expected if the test item is applied for 24h and because of that these reactions were devaluated. Additionally, less reading was done in some 24h application studies and sometimes the study was terminated to early which degrades the study worth for classification. Further in some old studies ( e.g. Cytec, Bio/Dynamics, 1984) the application area was no washed after patch removal. This can be assumed if the study is not conducted according to OECD. In result the non removal of the substance also increases contact time suggesting a much higher irritation level than determined with an OECD study.


In summary, company data and less documented studies were rated as less of reliability and 24h application studies as well as studies without washing after patch removal were classified as less of relevance for classification as the contact time to the test item is much longer than according to OECD guideline.


Taken together for risk assessment and classification only OECD guided studies were rated as useful for deriving the skin irritation potential. No to very slight skin irritation can be observed if the substance is applied for 4h. This result could be repeated four times with different batches. The only study showing slight reaction shows reversibility of effects at latest by day 3.


 


Key study assignment skin irritation:


Due to the good documentation and the guideline conformity, Cytec studies and BASF OECD studies are suitable as key studies. As one of the conducted OECD conform studies shows very slight effects whereas all other studies report no effects this study is assigned as key study. Additionally, this study is also the latest performed. In result the applicant assigns the BASF study (BASF, 2002) as key study as it is a reliable and relevant study with the most critical result conducted OECD guided.


 


Eye irritation:


Other guideline conform studies:


To investigate the eye irritating potential of TMPeoTA an eye irritation study was performed according to the rules of EPA TSCA und GLP (Cognis, Food & Drug Research Laboratories, 1984). Therefore 0.1ml test substance was instilled in one eye of 6 rabbits (New Zealand White). A second experiment was conducted where the eyes of 3 rabbits were washed after 30 sec of test item instillation. Gradings of irritation were recorded after 1h; 24h; 48h; 72h; daily during day 7 and every 3 days until day 21 if the effect is already there. Without washout mildly to moderate irritating effect were observed (opacity 1 (max 4); iritis 1 (max 2); conjunctiva redness 1.9 (max 3) and chemosis 2 (max 4)). All effects were reversible within at least 10 days.


A study was conducted to evaluate the ocular toxicity of TMPeoTA (Liquid polyol acrylate) in rabbits. The study was performed according to the EU Method B.5 (Acute toxicity: Eye irritation/corrosion) (Cytec, Huntingdon, 1993). 0.1 mL of the test substance was instilled into the eye of three New Zealand White rabbits; the contralateral eye served as an untreated control. One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed (pilot animal). Irritation was scored after 1 h of instillation and on Day 1, 2, 3, 4, 7 and 14. Corneal opacification (diffuse or easily discernible) was recorded between one and seven days after instillation of the test substance, and was accompanied by swelling of the cornea for one animal. Iridial inflammation was recorded for all three animals, lasting up to four days after instillation. The response was severe for one animal. Diffuse, crimson colouration of the conjunctivae was recorded for all three animals 1 h following instillation of the test material. This progressed to diffuse beefy red for all animals and was accompanied by obvious swelling of the lids. The swelling was with the lids about half-closed for one animal and with the lids more than half-closed for one other animal. Mean scores are as follows: cornea score 1.11, iris score 0.33, redness 2.56 and chemosis 2.44. The eyes of surviving animals were normal 7 or 14 days after instillation. One animal was killed on humane grounds four days after instillation of the test material. The animal was showing a pain response as a result of severe eye reactions caused by instillation of the test material. There were no other signs of toxicity or ill health in any rabbit during the observation period. In conclusion, TMPeoTA was considered to be irritating to rabbit eyes.


 


OECD guideline conform studies:


The potential of TMPeoTA to cause damage to the conjunctiva, Iris or cornea was assessed in 3 White New Zealand rabbits, subjected to a single ocular application of 0.1 ml of the test substance according to OECD 405 (BASF, 2002). The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and then in weekly intervals until day 14. Slight to severe conjunctival redness, slight to marked conjunctival swelling and slight to severe discharge were observed during the course of the study. Slight corneal opacity was observed in all animals and moderate or severe iritis was noted in two animals during the observation period. The ocular reactions were reversible in all animals within 14 days after application. The average score (24 to 72 hours) for irritation was calculated to be 1.0 for corneal opacity, 0.7 for iris, 2.6 for conjunctival redness and 2.1 for chemosis.


In another eye irritation study TMPeoTA was investigated according to OECD 405 guideline (BASF, 1991). Therefore 0.1ml of the test substance was instilled into the eye of 3 rabbits (Vienna White). No washout was performed and gradings were recorded after 1h, 24h, 48h, 72h, 8d, 17d and 23d. The untreated eye serves as negative control. Slight opacity (1 (max 4)) and iris lesions (0.4 (max 2) as well as well-defined conjunctiva redness (2.3 (max 3)) and chemosis ( 1.6 (max 4)) were calculated as mean of 24h, 48h and 72h reading. The irritation effect still appears in one animal after 23d. BASF REMARK: Cornea score of 1 in 1/3 animals on day 23 is considered to be a residual finding and not taken into account for classification, as no serious eye damage was observed in another test with another Laromer which contains > 83 % of CAS # 28961-43-5. In addition, there are several other studies available where no serious eye damage was observed.


In a further study the primary irritation potential of the test article was investigated by instillation of 0.1 ml into one eye of each of three young adult New Zealand White rabbits according to OECD 405 (Rahn, RCC Ltd., 1999). The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7 days after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. Slight opacity was observed in all animals 48 hours after administration. Slightly to moderately reddened conjunctivae was observed in all animals from the 1- to the 72-hour reading as well as swollen nictitating membrane and/or slight swelling of the eyelids in both females from the 24- to the 48- or 72-hour reading. Slight to moderate watery discharge was observed in the females between the 1- and 72-hour reading. Mean scores are as follows: cornea score 0.33, iris score 0.11, redness 1.22 and chemosis 0.56. All eye reactions were clear within 7 days after treatment.


 


Assessment eye irritation:


All available information is taken into account to assess the eye irritating potential of TMPeoTA.


All studies available were conducted according to OECD guideline or to similar protocols. Therefore all information available is used for risk assessment. All studies report about slight to severe eye irritation. Most studies point to gradings for cornea opacity around 1.0, iris lesion around 0.7, redness around 2.3 and chemosis around 2.0. A clear eye irritating effect could be expected from these results. Whereas most studies reported that the reactions were reversible within at latest 14 days one study (BASF, 1991) reported about still existing effects in one animal after 23 days. This finding was considered by the authors to be a residual finding and was therefore not taken into account for classification and assessment. As irreversible eye damage was not observed in any other tests and most tests results showed a fast reversibility the applicant follows the argumentation of the BASF study authors. Concluding the slight irritation seen after 23 days in one rabbit is rated as not relevant for assessment. In one other study (Cytec, Huntingdon, 1993) it is reported that one rabbit was killed on human grounds four days after test item application. No further explanation is given in the report but gradings reported there are comparable to the gradings in other studies. As no other study reported about such pain reaction after four days in any animal this finding/laboratory behaviour (killing the animal) is supposed to be subordinated.


In summary, all data on eye irritation was taken into account, leading to a clear eye irritating potential of the substance. Nevertheless signs for corrosion were not observed and reversibility was seen in all studies (except one BASF study, see remark).


 


Key study assignment eye irritation:


All studies available are well document and conducted. As all studies are performed according to an adequate guideline, all studies could be integrated as key studies. As all studies are equal in quality and report about similar irritation all studies are useable as key study. Nevertheless the study from BASF (BASF, 2002) according to OECD represents some of the most critical results and was the latest conducted study without any unusual finding like residual effects in one animal or unclear high pain reaction observed in one animal. Therefore this study (BASF, 2002) is used as key study.


 


Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation:

As according to GHS an application of 4h under GLP condition and OECD guideline is preferred to evaluate the skin irritation potential. Only studies fulfilling these criteria were used for classification.

Slight skin irritating effects were observed in one of four conducted studies according to OECD guideline. The scores obtained from the studies led to no classification according to GHS EC 1272/2008 as the mean value are below 2.3 for erythema/eschar or oedema in at least 2 of 3 animals and as the inflammation does not persist in 2 animals over a 14 day observation period. This result is underlined by the by the result of the other studies, where no skin irritation was observed.

Labelling for skin irritation:

GHS: no classification

Eye irritation:

Clear eye irritating effects were observed in five relevant and reliable eye irritation studies. The scores obtained in these studies led to a classification as an irritating to eye (cat. 2) due to criteria of classification EC 1272/2008 and Xi R-36 according to EU-criteria (67/548/EEC). This classification is based on the fact that more than 2 animals in four studies showed a cornea damage above 1 and that more than two animals had an iritis above 1 in two studies. For more than two animal there was also redness and chemosis reported in three and four studies respectively. 

Nevertheless, as there was no opacity above 3, iritis above 1.5 and all animals were free of signs within at latest 21 days (except the BASF study, which was rated as residual effect, see remarks and assessment) in all relevant studies therefore no higher classification is justified.

Labelling for eye irritation:

GHS: irritating to eye (cat. 2)