Trientine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August4-19,1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was performed according to OECD 404 guideline and GLP regulations, there were no deviations from these regulations. No data on purity were indicated.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

stability/purity not reported

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Trientine

EC Number:

203-950-6

EC Name:

Trientine

Cas Number:

112-24-3

Molecular formula:

C6H18N4

IUPAC Name:

N,N'-bis(2-aminoethyl)ethane-1,2-diamine

Details on test material:

- Name of test material (as cited in study report): 6933-6-20
- Physical state: clear, yellow liquid
- Analytical purity: no data
- Stability under test conditions: no apparent change in the physical state of the test article
- Amount received: 662.77 g (gross weight)
- pH: 8 (litmus paper)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products, Denver, PA
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 2.325-2.607kg
- Housing:Rabbits were housed individually in cages sized in accordance with the ''Guide for the Care and Use of Labolatory Animals'' of the Institute of National Research Council.
- Diet (e.g. ad libitum): Purina Lab Rabbit Chow (H.F.) ad libitum
- Water (e.g. ad libitum):fresh tap water, ad libitum
- Acclimation period: minimum 5d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C (63°-73°F)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light):12h light, 12h dark

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: shaved and abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL/site (6 cm²)
- Concentration (if solution):

Duration of treatment / exposure:

The test article was administrated once per site:
-3 min, 60 min, 4h, 24 h

Observation period:

14d

Number of animals:

Six (6) :3♂ and 3♀

Details on study design:

TEST SITE
- Area of exposure: 5 sites on the dorsal trunk
- % coverage:
- Type of wrap if used: impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): by using water and a gauze
- Time after start of exposure: 3 min, 60min, 4h, 24h


SCORING SYSTEM:
Draize Evaluation of Dermal Irritation, Primary Irritation Index

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4h exposure

Score:

8

Remarks on result:

other: severe dermal irritation at 4 and 24h exposure

Results 2

Irritation parameter:

erythema score

Basis:

animal: 6 animals

Time point:

other: 3min

Score:

>= 0 - <= 2

Max. score:

4

Results 3

Irritation parameter:

edema score

Basis:

animal: 6 animals

Time point:

other: 3 min

Score:

>= 0

Max. score:

4

Results 4

Irritation parameter:

erythema score

Basis:

animal: 5/6 animals

Time point:

other: 24h - 14 days

Score:

>= 4

Max. score:

4

Remarks on result:

other: necrosis

Results 5

Irritation parameter:

edema score

Basis:

animal: 5/6 animals

Time point:

other: 24h - 14 days

Score:

>= 4

Max. score:

4

Results 6

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24h

Score:

>= 1

Max. score:

4

Results 7

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24h

Score:

>= 1

Max. score:

4

Results 8

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 48h

Score:

>= 2

Max. score:

4

Results 9

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 48h

Score:

>= 0

Max. score:

4

Results 10

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 72h

Score:

>= 4

Max. score:

4

Remarks on result:

other: necrosis

Results 11

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 72h

Score:

>= 4

Max. score:

4

Irritant / corrosive response data:

results in above table are observed after 3 min exposure (except PDII).
animals have been exposed for 60min, 4h, and 24h. All animals scored 4 (necrosis) for erythema and edema immediately after unwrapping.
Severe erythema and severe edema remained present in all animals at all observation periods during the study (up to 14 days).

Any other information on results incl. tables

 

Animal No.	Sex	Body Weight Initial (kg)	Body weight Final (kg)
1	M	2.405	2.752
2	M	2.514	2.707
3	M	2.387	2.673
4	F	2.591	2.847
6	F	2.607	2.903
6	F	2.325	2.495

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The test article was considered to be severe dermal irritant at both 4 and 24 hour exposures.
The Dermal Irritation Toxicity Category is Class I (corrosive).
The DOT Packing Group Classification is Class I (corrosive at less than 3 min).
Primary Dermal Irritation Index at 4h and 24h exposure=8.00 (according to Draize scoring system).

Executive summary:

TETA was examined undiluted for skin irritation in groups of 3 rabbits per sex. The test material was applied (occlusive) directly on the intact and abraded skin sites. The skin was abraded using a burred needle, the abrasion penetrated the stratum corneum, but not the derma. The test article was administrated once per site for 3 min, 60 min, 4h, or 24 h. Necrosis was observed after 3 min exposure. The animals that had been exposed for 60 min, 4 h, or 24h scored 4 (necrosis) for erythema and edema immediately after unwrapping. Severe erythema and severe edema remained present in all animals at all observation periods during the study (up to 14 days).