O-(ethoxycarbonyl)-N-(1-methyl-2-oxo-2-phenylethylidene)hydroxylamine

Endpoint summary

Description of key information

Under the conditions of this study, the acute oral LD50 value in female Wistar rats was greater than 2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 June 2017 to 19 July 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks of age
- Weight at study initiation: 170 to 182 g
- Fasting period before study: Overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing.
- Housing: The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with wood-flakes.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 30 to 70 %
- Air changes: At least fifteen changes per hour
- Photoperiod: Lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg
- For the purpose of the study the test material was freshly prepared, as required, as a suspension in arachis oil BP. The test material was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

Doses:

- 300 mg/kg (as a starting dose; 30 mg/mL) and 2000 mg/kg (200 mg/mL)

No. of animals per sex per dose:

1 female animals at 300 mg/kg.
5 female animals at 2000 mg/kg.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes, at the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Preliminary study:

- One animal was treated at 300 mg/kg. The animal showed no signs of mortality or systemic toxicity. The animal showed expected gains in body weight over the observation period. No abnormalities were noted at necropsy.
- As a result the next animal was treated at 2000 mg/kg.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- There was no mortality in the study period.

Clinical signs:

other: - Hunched posture and ataxia were noted in all animals. - Lethargy and/or pilo-erection were also noted in three animals. - Tiptoe gait was confined to one animal. - Animals appeared normal 2 or 3 days after dosing.

Gross pathology:

- No abnormalities were noted at necropsy.

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of this study, the oral LD50 value in female Wistar rats was greater than 2000 mg/kg body weight.

Executive summary:

The acute oral toxicity potential of the test material to the rat was investigated in accordance with the standardised guidelines OECD 420 and EU Method B1 bis under GLP conditions.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of the test material, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths observed. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were hunched posture, ataxia, pilo erection, tiptoe gait and lethargy. Animals treated at a dose level of 2000 mg/kg appeared normal 2 or 3 days after dosing. There were no signs of systemic toxicity noted in the animal treated at a dose level of 300 mg/kg. All animals showed expected gains in body weight. No abnormalities were noted at necropsy.

Under the conditions of this study, the acute oral LD50 value in female Wistar rats was greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The acute oral toxicity potential of the test material to the rat was investigated in accordance with the standardised guidelines OECD 420 and EU Method B1 bis under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of the test material, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths observed. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were hunched posture, ataxia, pilo erection, tiptoe gait and lethargy. Animals treated at a dose level of 2000 mg/kg appeared normal 2 or 3 days after dosing. There were no signs of systemic toxicity noted in the animal treated at a dose level of 300 mg/kg. All animals showed expected gains in body weight. No abnormalities were noted at necropsy.

Under the conditions of this study, the acute oral LD50 value in female Wistar rats was greater than 2000 mg/kg body weight.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity via the oral route.