O-ethylhydroxylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no data on substance purity)

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

O-ethylhydroxylamine

EC Number:

402-030-3

EC Name:

O-ethylhydroxylamine

Cas Number:

624-86-2

Molecular formula:

C2 H7 N O

IUPAC Name:

O-ethylhydroxylamine

Details on test material:

- CTL reference number: Y05460/002/001
- Name of test substance as cited in document: Substance H109360
- Identification of test sample as stated in report: 50% (w/v) aqueous solution (approx. 45% ethoxyamine and approx. 5% ethanol
- Appearance: clear aquesous solution
- Lot #: EFI-100
- Analytical purity: not specified

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Name as cited in study report: (SPF) Wistar derived albino rats (A1pk :AP strain)
- Source: Animal Breeding Unit, Imperial Chemical Industries PLC
- Age at study initiation: not specified
- Fasting period before study: Yes, overnight for up to 24 hours
- Weight at study initiation: 243-353g for males and 180-220g for females
- Housing: maximum of 5 rats/sex/cage (Makrolon cages)
- Diet: (Porton Combined Diet, Special Diets Services Ltd provided ad libitum
- Water: ad libitum (automatic watering system)
Diet and water analysis indicated no contaminations that would influence the outcome of the study.
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-24
- Humidity (%): 40-60
- Air changes (per hr): 20-30
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10ml/kg bw

VEHICLE
- Concentration of test substance in vehicle (nominal) : 10.0, 25.0 and 50.0 mg/ml
- Concentration of test substance in vehicle (analysed) : 9.8, 23.0, 52.3 mg/ml

ANALYSIS OF TEST ARTICLE CONCENTRATION
- Method: Analysis was by gas chromatography using a Tenax TA column with a flame ionisation detector

Doses:

100, 250, 500 mg/kg bw (nominal)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: on the day before dosing (Day-1), the day of dosing (Day 1) and on Day 3, Day 6, Day 8 and Day 15
- Frequency of observations: twice between 14 and 90 minutes after dosing and twice again between 2 and 6 hours after dosing. Subsequent observations were made once daily up to Day 15
- Necropsy of survivors performed: yes

Statistics:

The acute oral median lethal dose (LD50) and the 95 confidence limits were estimated for the males from the mortality data the mortality data included animals that were killed in extremis) by the probit method using nominal dose values. The acute oral median lethal dose (LD50) for the females was estimated using linear log-dose interpolation. Approximate lower and upper confidence limits are given by the highest dose with no mortalities and the lowest dose with 100% mortality

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

177 mg/kg bw

Based on:

act. ingr.

Mortality:

- 100 mg/kg bw: 0/10
- 250 mg/kg bw: 1m/10 (killed in extremis on day 1)
- 500 mg/kg bw:9 (4m, 5f)/10 (killed in extremis or found dead on day 1)

Clinical signs:

- 100 mg/kg bw: no findings
- 250 and 500 mg/kg bw: most of the animals showed findings on day 1 persisting in one animal up to day 4, most common signs were: decreased activity, tonic convulsions, cyanosis, piloerection, upward curvature of the spine, reduced righting reflex, decreased breathing rate and increased breathing depth. The signs were consistent with the test sample acting either as a CNS depressant at the CNS respiratory centre and/or that the compound may induce methemoglobinemia. The effects were short-lived indicating rapid metabolism, detoxification and excretion.

Body weight:

no test sample-related effect on body weight, body weight gain.

Gross pathology:

No macroscopic abnormalities were detected at necropsy .

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test substance H109360 (O-ethylhydroxylamine) is considered to be toxic after a single oral adminsitration of >=177 mg/kg bw in both sexes.