Serine, 2-[(2,3,4-trihydroxyphenyl)methylene]hydrazide, hydrochloride (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Remarks:

Conducted according to guideline in effect at the time of study conduct.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Remarks:

Conducted according to guideline in effect at the time of study conduct.

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-3-hydroxy-N'-[(E)-(2,3,4-trihydroxyphenyl)methylidene]propanehydrazide hydrochloride

EC Number:

940-411-0

Cas Number:

1353749-74-2

Molecular formula:

C10H14ClN3O5

IUPAC Name:

2-amino-3-hydroxy-N'-[(E)-(2,3,4-trihydroxyphenyl)methylidene]propanehydrazide hydrochloride

Details on test material:

Purity: 100%

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Approximately 10, 11, or 12 weeks old
- Weight at study initiation: 205.5-256.1 g on test day 1
- Fasting period before study: Approximately 16.25 to 18 hours prior to dosing, with food being returned to the rats approximately 2.75 to 4 hours after dosing
- Housing: Individually in solid-bottom caging with bedding and appropriate species-specific enrichment
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 or 6-days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26ºC
- Humidity (%): 30-70%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): approximate 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% methylcellulose with 0.1% Tween-80

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: At dose levels of 175, 550, and 1750 mg/kg, the dose volume was 10 mL/kg body weight. At the dose level of 5000 mg/kg, the dose volume was 20 mL/kg body weight.

Doses:

175, 550, 1750, 5000 mg/kg

No. of animals per sex per dose:

1 at 175 and 550 mg/kg
3 at 1750 mg/kg
4 at 5000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Observations for mortality and signs of illness, injury, or abnormal behaviour were made daily throughout the study. The rats were observed for clinical signs at the beginning of fasting, just before dosing (test day 1), once during the first 30 minutes after dosing and 2 more times on the day of dosing, and once each day thereafter.
- Frequency of weighing: at death and on test days -1, 1, 8, and 15
- Necropsy of survivors performed: yes

Statistics:

AOT425statpgm (Version: 1.0) was used to determine the dose progression and to estimate the LD50.
Acute Oral Toxicity (OECD Test Guideline 425) Statistical Program

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Based on:

test mat.

95% CL:

2 016 - 9 810

Mortality:

Death occurred in 3 out of the 4 rats dosed at 5000 mg/kg (euthanized between test days 3 and 6). There were no deaths at lower doses.

Clinical signs:

other: No clinical signs were observed in the rat dosed at 175 mg/kg. Bright yellow staining was observed in the bedding of all rats dosed at 550 mg/kg and above, starting on the day of dosing and ending by test day 7. The yellow colour may be due to a possible

Gross pathology:

Gross lesions were limited to rats in the 5000 mg/kg group. All rats in this group had gross lesions and 3/4 were unscheduled sacrifices (2 on day 3, 1 on day 6). At 5000 mg/kg, 3/4 rats had red or black stomach discoloration and 1/4 rats had stomach (nonglandular portion) ulcer/erosion. Also, 2/4 rats had pale liver discoloration and 1/4 had red stained skin on the nose at the 5000 mg/kg dose level. No other gross lesions were observed.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 = 5000 mg/kg
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).

Executive summary:

A single oral dose of the test substance, suspended in 0.5% methylcellulose with 0.1% Tween-80, was administered by oral gavage to 9 fasted female rats at a dose of 175, 550, 1750, or 5000 mg/kg. The rats were dosed one at a time at a minimum of 48-hour intervals. All rats were observed for mortality, body weight effects, and clinical signs for 14 days after dosing. The rats were necropsied to detect grossly observable evidence of organ or tissue damage.

Death occurred in 3 out of the 4 rats dosed at 5000 mg/kg. There were no deaths at lower doses. Bright yellow staining was observed in the bedding of all rats dosed at 550 mg/kg and above, between test days 1 and 6. The yellow colour may be due to a possible product of the test substance. Rats dosed at 1750 mg/kg exhibited ataxia, decreased muscle tone, high posture, low posture, and/or black perinasal staining between test days 1 and 7. Rats dosed at 5000 mg/kg exhibited ataxia, abnormal gait, lack of food consumption, high posture, low posture, fast breathing, dehydration, moribundity, decreased muscle tone, brown perinasal or forelimb staining, bright yellow inguinal/perineal staining, coldness to touch, pallor, prostration, and/or slow/absent righting reflex between test days 1 and 11. No clinical signs were observed in the rat dosed at 175 mg/kg. Gross lesions were limited to rats in the 5000 mg/kg group. All rats in this group had gross lesions and 3/4 were unscheduled sacrifices (2 on day 3, 1 on day 6). At 5000 mg/kg, 3/4 rats had red or black stomach discoloration and 1/4 rats had stomach (nonglandular portion) ulcer/erosion. Also, 2/4 rats had pale liver discoloration and 1/4 had red stained skin on the nose at the 5000 mg/kg dose level. No other gross lesions were observed. Under the conditions of this study, the oral LD₅₀ for the test substance was 5000 mg/kg for female rats.