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Description of key information

Two skin irritation studies are available.  The 1986 study was conducted in accordance with GLPs and is better documented and therefore selected as the key study.  Three eye irritation studies are avaialble which all demonstrate no adverse effect.  

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

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Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Because the purity of the substance tested is not given in the study report, it is not possible to ascertain the degree to which the results represent the pure submission substance.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Healthy male, young adult, New Zealand White albino rabbits obtained from ENKI-Konijnenfarm, Someren, the Netherlands, were used as the experimental animals. The body weight range was 2500-3500 g. The animals were identified by earmarking.The animals were housed individually in suspended, galvanized cages, fitted with wire-mesh floor and front. The cages were placed in a room, controlled for light (12 hours light/dark cycle), temperature (18+/-3°C), ventilation (c. 10 air changes/hour), and relative humidity (40-70%) throughout the test period. A standard laboratory rabbit diet and tap water were provided ad libitum.
Type of coverage:
occlusive
Preparation of test site:
other: shaved; abraded and unabraded
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 ml per site
Duration of treatment / exposure:
After an exposure period of 4 hours the patches and the test material applied were removed and the resulting skin reactions were evaluated by the method of Draize et a1. (J. Pharmaco1. Exp. Ther. 82 (1944) 377-390).
Observation period:
8 days
Number of animals:
six; male
Details on study design:
After an acclimatization period of six days, i.e. one day prior to the start of the experiment, the hair was removed from the back and flanks of the animals using electric clippers in a way as to avoid abrasions. Six rabbits were treated on the intact skin and on the abraded skin. The abrasions were minor incisions of the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding. An amount of 0.5 m1 of the undiluted test substance was brought onto the intact and the abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches were fixed to the application site by means of adhesive tape and the entire trunk of each rabbit was wrapped with an impervious material to maintain the test patches in position and to retard evaporation of the test substance. After an exposure period of 4 hours the patches and the test material applied were removed and the resulting skin reactions were evaluated by the method of Draize et a1. (J. Pharmaco1. Exp. Ther. 82 (1944) 377-390). Further readings were made after 28, 52 and 76 hours.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 52 hours
Score:
5.7
Max. score:
6
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: After eight days, slight scaliness was observed in all (six) rabbits. In earlier studies conducted in this Institute it was observed that dermal effects such as slight scaliness seen one week after application of a test substance, were fully reversible.
Interpretation of results:
Category 2 (irritant)
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test substance generally caused well-defined or moderate erythema and very slight to slight ischemia in all (six) rabbits. In addition, slight scaliness and very slight incrustation was observed in a limited number of animals. The reactions of the abraded skin were slightly more pronounced than those of the intact skin, but all reactions were considered to be reversible. On the basis of the results obtained it was concluded that, according to the EEC-standards*, the undiluted test substance Trigonox C is a primary skin irritant.
* EEC Directive 79-831, Annex V, Part B: Methods for the determination of toxicity, B.4. Acute toxicity, skin irritation, dated December 1983.
Executive summary:

A sample of Trigonox C was examined undiluted for primary skin irritating properties in an experiment with six albino rabbits. The test substance generally caused well-defined or moderate erythema and very slight to slight ischemia in all (six) rabbits. In addition, slight scaliness and very slight incrustation was observed in a limited number of animals. The reactions of the abraded skin were slightly more pronounced than those of the intact skin, but all reactions were considered to be reversible. On the basis of the results obtained it was concluded that, according to the EEC-standards*, the undiluted test substance Trigonox C is a primary skin irritant.

* EEC Directive 79-831, Annex V, Part B: Methods for the determination of toxicity, B.4. Acute toxicity, skin irritation, dated December 1983.

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:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
72 hours
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Because the purity of the substance tested is not given in the study report, it is not possible to ascertain the degree to which the results represent the pure submission substance.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Healthy male, young adult, New Zealand White albino rabbits obtained from ENKI-Konijnenfarm, Someren, the Netherlands, were used as the experimental animals. The body weight range was 2500-3500 g. The animals were identified by earmarking.The animals were housed individually in suspended, galvanized cages, fitted with wire-mesh floor and front. The cages were placed in a room, controlled for light (12 hours light/dark cycle), temperature (18+/-3°C), ventilation (c. 10 air changes/hour), and relative humidity (40-70%) throughout the test period. A standard laboratory rabbit diet and tap water were provided ad libitum.
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of each animal served as control
Amount / concentration applied:
0.1 ml - One tenth of a milliliter of the undiluted test substance was allowed to fall on the everted lower lid of one eye of each rabbit.
Duration of treatment / exposure:
After administration the upper and lower lid were carefully closed and subsequently held together for about one second before releasing, to prevent loss of material.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
Both eyes of each rabbit provisionally selected were examined within 24 hours before testing; three animals without observable eye defects were used. One tenth of a milliliter of the undiluted test substance was allowed tofall on the everted lower lid of one eye of each rabbit. After administration the upper and lower lid were carefully closed and subsequently held together for about one second before releasing, to prevent loss of material. The other eye remaining untreated, served as a control. The eyes were not washed out following administration and the animals were released immediately. Ocular reactions were judged using a scoring scale which is part of the attached complete report. Eye effects were examined after one hour, 24, 48 and 72 hours.
Irritation parameter:
other: Maximum score recorded
Basis:
animal #2
Time point:
other: 1 hour
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
maximum score, any animal @ 1, 48 and 72 hours, respectively: 2*, 1*, 0

*chemosis and redness
Other effects:
none
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test substance caused slight or moderate redness and slight or moderate swelling of the conjunctivae in all (three) rabbits. After 72 hours, all eye effects had cleared completely. On the basis of the results obtained it was concluded that, according to the EEC-standards*, the undiluted test substance Trigonox C is not an eye irritant.
*EEC Directive 79-831, Annex V, Methods for the determination of toxicity, B.5. Acute toxicity, eye irritation, dated December 1983.
Executive summary:

The test substance caused slight or moderate redness and slight or moderate swelling of the conjunctivae in all (three) rabbits. After 72 hours, all eye effects had cleared completely. On the basis of the results obtained it was concluded that, according to the EEC-standards*, the undiluted test substance Trigonox C is not an eye irritant.

*EEC Directive 79-831, Annex V, Methods for the determination of toxicity, B.5. Acute toxicity, eye irritation, dated December 1983.

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:
no adverse effect observed (not irritating)

Respiratory irritation

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

Additional information

EC GHS Category 2 Skin irritation response. Well defined to moderate erythema and slight ischemia in all six test subjects. Reactions judged reversible.

EC GHS Not classified as an eye irritant. The calculated mean scores following grading at 24, 48 and 72 hours did not meet or exceed the criteria for classification.

Justification for selection of skin irritation / corrosion endpoint:

Reliable study conducted in accordance with GLPs.  

Justification for selection of eye irritation endpoint:

Reliable study.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

EC GHS Category 2 Skin irritation response. Well defined to moderate erythema and slight ischemia in all six test subjects. Reactions judged reversible.

EC GHS Not classified as an eye irritant. The calculated mean scores following grading at 24, 48 and 72 hours did not meet or exceed the criteria for classification.