Trientine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was performed according to OECD 402 guideline and in compliance with the GLP Regulations.No significant deviations can be observed from the study guidelines, which could have an impact on the performed study. Data on purity are, however, not indicated.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

purity not reported

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

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): 6933-6-2
- Physical state: clear, yellow liquid
- Analytical purity: no data
- Stability under test conditions: no apparent change in the physical state of the test article during storage
- Storage condition of test material: no data
- Other: specific gravity= 0.9800 g/mL

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Denver PA
- Age at study initiation: young adults
- Weight at study initiation: 1.943-2.800 kg
- Fasting period before study: No
- Housing:individually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council.
- Diet (e.g. ad libitum): Purina Lab Rabbit Chow H.F.
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: min. 5d


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


IN-LIFE DATES: From: 1992-11-30 To:

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of trunk (clipped free of fur)
- Type of wrap if used: rubber dam and an elastic bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with water and gauze
- Time after start of exposure: 24h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1000, 2000 and 3000 mg/kg
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

1000, 2000 and 3000 mg/kg

No. of animals per sex per dose:

10 ( 5♂and 5♀)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily through 14 days; body weight: d0,d7 and d14 or when dead
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal observations

Statistics:

By the method of Litchfield and Wilcoxon via the Innovative Programming Associates, LABCAT Module Version 4.24.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 465.4 mg/kg bw

95% CL:

1 074.6 - 1 998.3

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 720 mg/kg bw

95% CL:

1 082.9 - 2 732

Mortality:

-2/10 animals died at the 1000 mg/kg dose level
-8/10 animals died at the 2000 mg/kg dose level
-9/10 animals died at the 3000 mg/kg dose level

Clinical signs:

other: - DECREASED ACTIVITY: 2/10 animals at 1000 mg/kg dose level;7/10 animals at 2000 mg/kg dose level;6/10 animals at 3000 mg/kg dose level; -ABNORMAL GAIT: 1/10 animals at 1000 & 3000 mg/kg dose level; 6/10 animals at 2000 mg/kg dose level - ABNORMAL STANC

Gross pathology:

Necropsy of the animals that died on study revealed discolored and/or fluid-filled stomach, distended and/or fluid-filled intestines, discolored kidneys and liver, fluid-filled bladder and necrosis of the skin at the application site.
Terminal necropsy revealed discolored lungs in one animal and necrosis of the skin at the application site in all of the animals. No other visible lesions were observed in any animal at terminal necropsy .

Any other information on results incl. tables

The data generated for the acute dermal LD50 in females did not lend itself to the statistical method applied

Applicant's summary and conclusion

Conclusions:

Based on the observations made in the Acute Exposure Dermal Toxicity Study in rabbits, the acute dermal LD50 in males and combined sexes for 6933-6-20 was determined to be 1720.0 (1082.9-2732.0) mg/kg and 1465.4 (1074.6-1998.3) mg/kg, respectively. The data generated for the acute dermal LD50 in females did not lend itself to the statistical method employed.