Digadolinium trioxide

Endpoint summary

Description of key information

Skin irritation/corrosion

The test item was not irritating to skin in a reliable in vivo skin irritation test in rabbits, following 24 hours exposure to 0.5 g at an intact and an abraded test site (Lambert et al., 1993). An in vitro study does not need to be conducted as adequate data from an in vivo study is available. The test substance is not irritating to skin and does not need to be classified according to the CLP Regulation.

Eye irritation

The test item was described as producing minimal irritation to both unwashed and washed eyes upon instillation of 0.1 g in 6 rabbits (Shapiro, 1990b). Based on the individual data for cornea opacity, iritis, conjunctival redness and chemosis, no classification of the test substance according to the CLP Regulation is required. In vitro studies do not need to be conducted as adequate data from an in vivo study is available.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Study conducted in accordance with generally accepted scientific principles, with incomplete reporting or methodological deficiencies. However, as most basic key information is reported, the study can be judged as scientifically acceptable. In order to limit animal testing, no other assay was conducted.

Qualifier:

according to guideline

Guideline:

other: US guideline, not specified in the source publication

Principles of method if other than guideline:

The test item was applied on intact and abraded skin of New Zealand Albino rabbits and occluded for 24 h. Sites were evaluated 24 and 72 h after initial exposure according to the method of Draize.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
No further data available.

ENVIRONMENTAL CONDITIONS
No further data available.

IN-LIFE DATES: No further data available.

Type of coverage:

occlusive

Preparation of test site:

other:

Remarks:

One intact and one abraded skin site per animal was treated

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

undiluted / 0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

72 hours
The sites were evaluated 24 and 72 hours after initial exposure.

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: ca. 2.5 cm²
- % coverage: No data
- Type of wrap if used: No data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes (the test sites were wiped)
- Time after start of exposure: 24 hours

SCORING SYSTEM:
- Method of calculation: According to Draize (1944)

Irritation parameter:

primary dermal irritation index (PDII)

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

measured at 24 h and 72 h

Irritant / corrosive response data:

There were no signs of dermal irritation.

Interpretation of results:

GHS criteria not met

Remarks:

not irritating

Conclusions:

The test material was not irritating under the conditions of this test. Therefore, the test item is not classified according to CLP regulation.

Reference 2

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

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-10-24 to 1990-11-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

equivalent or similar to guideline

Guideline:

other: FHSA 16 CFR 1500.42

Deviations:

not specified

Principles of method if other than guideline:

No further data.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm, South Brunswick, NJ, USA
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: Individually housed in suspended stainless steel caging with mesh floors.
- Diet (e.g. ad libitum): ad libitum, Pelleted Purina Rabbit chow
- Water (e.g. ad libitum): ad libitum, tap water supplied by automatic watering system
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 66-76°F
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: 1990-12-31 To: 1991-01-03

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye of each animal remained untreated and served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Undiluted; 0.1 g was applied into the conjunctival sac of the right eye.

Duration of treatment / exposure:

30 seconds for 3 of the treated eyes (washed eyes) and up to 72 hours for the 3 others (the upper and lower lids were gently held together for about 1 second to prevent loss of the test material).

Observation period (in vivo):

72 hours (observation at 24, 48, and 72 hours after instillation)

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 3 of the treated eyes were rinsed with 30 mL saline 30 seconds post-instillation. The remaining three eyes were not irrigated.

SCORING SYSTEM: According to the method of Draize. The eye scores were further classified by the system of Kay and Calandra, Modified. Special care was taken to look for and notate any unusual effects, such as pannus, blistering of the conjunctivae, ulceration and other indicators of corrosive action.

The maximum mean total score (MMTS) was determined for both washed and unwashed eyes, and classification was determined as follows:
0.0-0.5 - non-irritating
0.6-2.5 - practically non-irritating
2.6-15.0 - minimally irritating
15.1-25.0 - mildly irritating
25.1-50.0 - moderately irritating
50.1 - 80.0 - severely irritating
80.1 - 100.0 - extremely irritating
100.1 - 110.0 - maximally irritating

If more than 40% of the rabbits tested have scores > 10 or if an individual rabbit score is > 30, the preliminary classification is raised to the next highest level.

Irritation parameter:

cornea opacity score

Basis:

animal: 1,2,3

Remarks:

unwashed eye

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal: 4,5,6

Remarks:

washed eye

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal: 1,2

Remarks:

unwashed eye

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal: 3

Remarks:

unwashed eye

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal: 4,5,6

Remarks:

washed eye

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal: 1,2

Remarks:

unwashed eye

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 3

Remarks:

unwashed eye

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks:

scores after 24, 48 and 72 h were 2, 1 and 1, respectively

Irritation parameter:

conjunctivae score

Basis:

animal: 4

Remarks:

washed eye

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 5

Remarks:

washed eye

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks:

scores after 24, 48 and 72 h were 1, 2 and 1, respectively

Irritation parameter:

conjunctivae score

Basis:

animal: 6

Remarks:

washed eye

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: 1,2

Remarks:

unwashed eye

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal: 3

Remarks:

unwashed eye

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks:

scores after 24, 48 and 72 h were 1, 1 and 1, respectively

Irritation parameter:

chemosis score

Basis:

animal: 4

Remarks:

washed eye

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: 5,6

Remarks:

washed eye

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

One unwashed and three washed eyes had iritis at 24 hours only. All animals had slight conjunctival irritation which had cleared from most treated eyes by 72 hours. No corneal opacity was noted during the study. The test material is considered to be minimally irritating to the unwashed eye and mildly irritating to the washed eye, when considering the Maximum Mean Total Scores.

Maximum Mean Total Score for washed eyes: 11.7
Maximum Mean total Score for unwashed eyes: 6.3

- mean of 3 rabbits / unwashed eyes at 24h: 6.3
- mean of 3 rabbits / unwashed eyes at 48h: 2.7
- mean of 3 rabbits / unwashed eyes at 72h: 1.3
- mean of 3 rabbits / washed eyes at 24h: 11.7
- mean of 3 rabbits / washed eyes at 48h: 4.0
- mean of 3 rabbits / washed eyes at 72h: 0.7

Interpretation of results:

GHS criteria not met

Conclusions:

The test material produced minimal irritation to both the unwashed and washed eyes. Based on the individual data for cornea opacity, iritis, conjunctival redness and chemosis, no classification of the test substance according to the CLP Regulation is required.

Reference 2

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 study available

Additional information

Skin irritation/corrosion

Only one reliable study is available (Lambert et al., 1993, scored Klimisch 2). The test item was administered to an intact and an abraded skin site in 6 rabbits, at an amount of 0.5 g and undiluted. After 24 hours of exposure, the sites were evaluated until 72 hours after initial exposure. The effects were scored according to Draize scoring system. There were no signs of dermal irritation, with the primary dermal irritation index determined to be 0.0. The test item is not irritant to skin. An in vitro study does not need to be conducted as adequate data from an in vivo study is available.

Eye irritation

Only one reliable study is available (Shapiro, 1990b, scored Klimisch 1). The test item was instilled in the right eye of 6 rabbits, with the left eye serving as control. An amount of 0.1 g was applied. Three eyes were washed, and three unwashed. One unwashed eye and three washed eyes had iritis at 24 hours only (score 0.33 for mean time point 24/48/72h). All animals had slight conjunctival irritation which cleared from most treated eyes by 72 hours. No corneal opacity was noted during the study. The test material is considered to be minimally irritating to the unwashed eye and mildly irritating to the washed eye, when considering the Maximum Mean Total Score. Based on individual data for corneal opacity, iritis, conjunctival redness and chemosis, the test item needs not to be classified as eye irritant according to the CLP Regulation. In vitro studies do not need to be conducted as adequate data from an in vivo study is available.

Justification for classification or non-classification

Skin irritation/corrosion

The test item is not irritant to skin and is therefore not to be classified according to the CLP regulation.

Eye irritation

Based on individual scoring for corneal opacity, iritis, conjunctival redness and chemosis, the test item needs not to be classified according to the CLP Regulation.