Ethanol, 2-amino-, reaction products with ammonia, by-products from, distn. Residues

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was performed according to following guidelines:OECD 401, EPA Federal Register Vol.50, No. 188 , (September 27, 1985) 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. Well-documented; however, no data on purity were given.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: EPA FR Vol.50, No. 188, September 27, 1985

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

purity and storage conditions are 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): 6933-6-20
- Physical state: clear yellow liquid
- Analytical purity: not given
- Lot/batch No.: 92-014
- Stability under test conditions: no apparent change in the physical state of the rest article during storage or administration
- Storage condition of test material: no data
- Other: specific gravity=0.98g/ml;

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc.,Wilmington, Massachusetts
- Age at study initiation: 6-10 weeks
- Weight at study initiation: 175-224 g
- Fasting period before study: yes
- Housing:individually in stainless steel 1/2'' wire mesh 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): Harlan Teklad Lab Blox, ad libitum
- Water (e.g. ad libitum):no data
- Acclimation period: min. 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C±3°C
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12h dark/12h light


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

800, 1250, 1600 and 2000 mg/kg

No. of animals per sex per dose:

10 (5♂ and 5♀)

Control animals:

other: not required according to OECD 401

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: pharmacological and toxicological effects: at 1,4 and 24 hours after dosing and once a day through 14 days ; viability: once a day;body weight: d0, d7 and d14 or were found dead
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other:

Statistics:

The method of Litchfield and Wilcoxon via Innovative programing Associates,LABCAT Module Version 4.22.

Results and discussion

Preliminary study:

Dose-range -finding: 3 groups of 2 rats (1♂ and 1♀ per group) fasted and administrated test article at the dose levels: 500, 2500 and 5000mg/kg, orally by gavage. 0/2 animal died at the 500mg/kg dose level; 2/2 animals died at both the 2500 and 5000mg/kg dose levels.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 861.9 mg/kg bw

95% CL:

1 383.5 - 2 505.7

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 591.4 mg/kg bw

95% CL:

1 283.5 - 1 973.3

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 716.2 mg/kg bw

95% CL:

1 446.5 - 2 036.1

Mortality:

0/10 animals died at both the 800 and the 1250mg/kg dose levels
5/10 animals died at the 1600 mg/kg dose level
7/10 animals died at the 2000 mg/kg dose level

Clinical signs:

other: decreased activity, abnormal gait, abnormal stance, prostration, diarrhea, lacrimation and dyspnea

Gross pathology:

Necropsy of the animals dying on study revealed fluid-filled and distended intestines and stomachs and discolored lungs and
intestines. No visible lesions were observed in any animal at terminal necropsy .

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

Based on the results from the Acute Exposure Oral Toxicity in rats, the acute oral LD50 for males, females and combined sexes was determined to be 1861.9 (1383.5 - 2505.7) mg/kg, 1591.4 (1283.5 - 1973.3) mg/kg and 1716.2 (1446.5 - 2036.1) mg/kg, respectively.

Executive summary:

An acute oral toxicity study with TETA was carried out in Sprague Dawley rats. Groups of 5 rats per sex were treated per gavage at 800, 1250, 1600 or 2000 mg/kg bw and were observed for 14 days therafter. Mortality was 0, 0, 50 and 70%, respectively. The acute oral LD50 for males, females and combined sexes was determined to be 1861.9 (1383.5 - 2505.7) mg/kg, 1591.4 (1283.5 - 1973.3) mg/kg and 1716.2 (1446.5 - 2036.1) mg/kg, respectively.