Reaction mass of trientine and trientine, mono- and di-propoxylated

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study Conducted in accordance with OECD test guideline but no details of whether this study was conducted in accordance with OECD

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of trientine and trientine, mono- and di-propoxylated

EC Number:

942-835-1

Molecular formula:

(C6 H18 N4 . C3 H6 O)x

IUPAC Name:

Reaction mass of trientine and trientine, mono- and di-propoxylated

Test material form:

other: Liquid

Details on test material:

Batch No.: EN 521687
Purity: Commercial grade
Physical properties: Liquid
Storage conditions: Room temperature
Expiry: July 1992
Received: 17 July 1989

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals were acclimatised to laboratory conditions for at least 5-days. The animals were housed individually in metal cages, identified by ear tattoo, kept at a constant room temperature of 20+3 °C, at a relative humidity of 30-70 % and on a 12 hours light cycle day. The rabbits received ad libitum standard rabbit pellet and fresh water. All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer.

The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). The results of the routine chemical examination of water at source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewaesserschütz ) are available to CIBA-GEIGY Limited, as well as the results of inhouse chemical analysis by
the analytical laboratories of the Pharmaceutical Division, CIBA-GEIGY Limited.

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

The patches were loosely covered with an aluminum foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape.

Observation period:

The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated 1, 24, 48, and 72 hours after
removing the gauze patches according to the OECD scoring system

Number of animals:

3 male rabbits

Details on study design:

An area of at least 36 cm was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm2)
bearing 0.5 ml of the test material was applied to the right flank of each animal. A control gauze patch moistened with distilled water was applied to the contralateral flank.

The patches were loosely covered with aluminum foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape. The animals were checked daily for systemic symptoms and mortality.

The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system

The irritant/corrosive potency of TK 10406 was classified according to the EEC Council Directive 83/467

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

429/M

Time point:

24/48/72 h

Score:

2.67

Reversibility:

fully reversible within: 14-days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

527/M

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 10 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

401/M

Time point:

24/48/72 h

Score:

0.167

Reversibility:

fully reversible

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

429/M

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

527F/M

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

401/M

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible

Irritant / corrosive response data:

The reactions were observed within 72 hours after removing the bandages, the observation period was extended to 14 days to determine
the reversibility of the skin reactions. According to the EEC classification of the results obtained 24 to 72 hours after removing the
bandages, the test material must be classified as irritant in albino rabbits.

The erythema and edema reactions observed were reversible until the end of the observation period on day 14.
In one animal the treated skin showed a yellowish discoloration 72 hours after patch removal, and on experimental day 7 a white crust was formed
within a small area of the exposed skin. Scaling was observed in this animal from day 7 until the final reading on day 14, and in another animal on
days 7 and 10 of the test.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

Migrated information

Executive summary:

An acute Dermal Irritation/Corrosion Study in the Rabbit was conducted in accordance with the OECD 404 test guideline. An area of at least 36 cm was shaved on both flanks of the animals (3 males) approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm2) bearing 0.5 ml of the test material was applied to the right flank of each animal. A control gauze patch moistened with distilled water was applied to the contralateral flank. The patches were loosely covered with aluminum foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape. The animals were checked daily for systemic symptoms and mortality.

The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system and the irritant/corrosive potency of the test material was classified according to the EEC Council Directive 83/467. The reactions were observed within 72 hours after removing the bandages, the observation period was extended to 14 days to determine the reversibility of the skin reactions. According to the EEC classification of the results obtained 24 to 72 hours after removing the bandages, the test material must be classified as irritant in albino rabbits. After 72 -hours, the mean irritation parameters for erythema and edema were 2.11 and 1.0 respectively. Because the mean values of the readings 24 to 72 hours after application are above the threshold of significance (score 2 for erythema or edema) the substance must be classified as irritant according to the EEC Council Directive 83/467. The erythema and edema reactions observed were reversible until the end of the observation period on day 14.