N-(2-ethoxyphenyl)-N'-(2-ethylphenyl)oxamide

Endpoint summary

Description of key information

Acute Toxicity (oral, rat, OECD 423): > 2000 mg/kg bw
Acute Toxicity (dermal, rat. similar to OECD 402): > 5000 mg/kg bw
Acute Toxicity (inhalation): data lacking  

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:

from 12th May 2014 to 27th May 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducetd according to international guidelines. No relevant deviations have been reported so that the study is considered reliable.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species, strain, weight:
Rats, Wistar, 160 – 180g – weight suits to age of animals 6 – 7 weeks.
Females were nulliparous and non-pregnant.

Number and sex:
From the ordered 9 female and 3 male animals only 3 females and 3 males were employed, as the conditions of limit test at the dose 2000 mg/kg were satisfied.
Normally females are used in the test according to OECD TG 423 because mostly females are more sensitive gender, but if a new product is tested, there is still a possibility that this assumption will not be confirmed. For this reason one dose in males was used to verify sensitivity of sexes. In time of application animals reached body weight 195 – 215 g females, and 250 g males what falls into recommended age 8 – 12 weeks.

Source:
Accredited Breeding Velaz Prague (CZ)

Identification:
The animals were housed in groups by 3 in cages after application. They were marked on tail and numbering the cage with indicating sex, dose and date of application.

Housing:
Animals were housed in experimental animal house on the bedding (Lignocel S 3/4, Lufa – ITL GmbH Germany) in groups by 3 in cages in conformity with laboratory animals welfare legislation.

Diet:
A standard certified laboratory diet (supplier MP – OŠ – 06 extrudes, Snina, Slovak Republic) was served. The diet was routinely analysed by the manufacturer for nutritional components and environmental contaminants and by the independent laboratory.

Water:
Bottled tap drinking water, routinely (quarterly) analysed by accredited laboratory, was accessible ad libitum.

Environment:
Environmental controls for the animal room were set to maintain 22 ± 2oC, a relative humidity of 55 ± 10 %. The temperature and relative humidity of air were recorded and the records are included in primary documentation. A minimum of 10 air changes/hour, and artificial light regime12 h light/12 h dark were implemented.

Acclimation:
The animals were acclimated under the conditions of the test seven days before the beginning of the treatment.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1%

Details on oral exposure:

The test item was administered in a single dose by gavage using a stomach tube. Animals were fasted prior to dosing (food but not water was withheld over- night). Following the period of fasting, the animals were weighed and the test item administered. After the test item has been administered, food was withheld for a further 3-4 hours.

Doses:

The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg. Available information indicated test item is likely to be nontoxic considering to acute toxicity.
A limit dose of 2000 mg/kg was used as starting dose. Group of 3 rats’ females were dosed.
As no test item-related mortality was produced additional group of 3 male rats were tested at the same dose no further dosing was necessary.

No. of animals per sex per dose:

From the ordered 9 female and 3 male animals only 3 females and 3 males were employed, as the conditions of limit test at the dose 2000 mg/kg were satisfied.

Control animals:

no

Details on study design:

Animals were observed individually immediately, ½, 1, 2, and 4 hours after application and daily thereafter, for a total of 14 days.
Additional observations were not necessary. Clinical signs and conditions associated with pain, suffering, and impending death, are described in detail in a separate OECD Guidance
Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. No animal was found in a moribund condition.

Individual weights of animals were determined shortly before the test item was administered and weekly thereafter. Weight changes after first and second weeks after application were calculated and recorded.

All test animals were subjected to gross necropsy. Full, detailed gross necropsy included careful examination of external surface of the body, all orifices, and cranial, thoracic and abdominal cavities and their contents. All gross pathological changes were recorded for each animal.

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All 3/3 females and 3/3 males survived the limit dose 2000 mg/kg. No further dosing was necessary.

Clinical signs:

other: Neither in females nor in males visible symptoms were observed at the dosage of 2000 mg/kg during first 4 hours after application or in 14 day observation period.

Gross pathology:

All 3 males and 3 females survived observation period and were necropsied after euthanasia.
During necropsy no macroscopically changes were noticed

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The test item applied to 3 males and 3 females in limit dose 2000 mg/kg did not cause death either visible symptoms of toxicity during 14 day observation period. It can be concluded that the LD50 of the test item UV 312 is ˃ 2000 mg/kg after single oral administration to Wistar rats.

Executive summary:

The objective of the study was to obtain information on the acute toxicity of test item when administered per orally in single dose to Wistar rats. The study was carried out in compliance with OECD TG 423 where the doses could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg. A limit dose of 2000 mg/kg was used as a starting dose. Groups of 3 females and 3 males were dosed. Since all 3/3 females and 3/3 males survived limit dose 2000 mg/kg no further dosing was necessary. The test item was applied to 3 males and 3 females. The limit dose 2000 mg/kg did not cause death, visible symptoms of toxicity during 14 day observation period or body weight loss. It can be concluded that LD50 of the test item is ˃ 2000 mg/kg, after single oral administration to Wistar rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The information is reliable and consistent with the database as a whole.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study pre-dating OECD protocolls and GLP requirements. However, slight shortcomings regards documentation (e.g.number of animals, number of animals per dose ) justify a Klimisch 2 rating (reliable with restrictions).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not applicable

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: CFY

Sex:

male

Details on test animals or test system and environmental conditions:

The male rats weighted from 236 to 242 grams.

Type of coverage:

occlusive

Vehicle:

other: the test item pulver was prepared as a 40% suspension in aqueous gum tragacanth (0.5%)

Details on dermal exposure:

One day prior to treatment, hair was removed from the dorso-lumbar region of each rat with electric clippers exposing an area equivalent to 10% of the total body surface. No shaving or chemical depilation was used.

Duration of exposure:

The exposure period was of 24 hours. The skin of the animals was then decontaminated by washing with warm (40-50°C) dilute soap solution, rinsing in clean warm water and finally blotting dry with absorbent paper. The decontamonated animals were returned to their cages for a subsequent observation period of 14 days, during which a record was kept of all signs of toxicity.

Doses:

The test item was prepared as a 40% suspension in aqueous gum tragacanth (0.5%) and administrated at a dosage volume of 12.5 ml/Kg bodyweight by spreading evenly over the prepared skin.

No. of animals per sex per dose:

no data

Control animals:

yes, concurrent vehicle

Details on study design:

The treated areas of skin were examined daily for signs of dermal irritation and assessed according to the following scoring system:

erythema and eschar formation:
no erythema 0
slight erythema 1
well-defined erythema 2
moderate to severe erythema 3
severe erythema (beet redness) to slight eschar formation 4
(injuries in depth)

Oedema formation:
No oedema 0
slight oedema 1
well-defined oedema (area well defined by definite raising) 2
moderate oedema (raised approximately 1 mm) 3
severe oedema (raised more than 1 mm and extending 4
beyond the area of exposure).

Statistics:

not applicable

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 other: g/Kg

Based on:

test mat.

Mortality:

There were no mortality or signs of toxicity.

Clinical signs:

other: Slight erythema was observed in one rat on the first three days following treatment.

Gross pathology:

Terminal autopsy findings were normal.

Other findings:

Control rats treated with the vehicle alone did not show any observable dermal reactions.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The acute median lethal percutaneous dose (LD50) to rats of Sanduvor pulver was found to be greater than 5.0 g/Kg bodyweight.

Executive summary:

An acute dermal toxicity study was conducted in male rats. The test item was prepared as a 40% suspension in aqueous gum tragacanth (0.5%) and administrated at a dosage volume of 12.5 ml/Kg bodyweight by spreading evenly over the prepared skin. There were no deaths in the study, and no evidence of systemic toxicities or local irritation. Based on the results, the acute dermal median lethal dose (LD50) in rats was determined to be greater than 5.0 g/Kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The information is reliable and consistent with the database as a whole.

Additional information

The potential acute oral toxicity of the test material was evaluated in male and female rats in a study conducted according to the OECD Guideline for the Testing of Chemicals No. 423. It has been concluded that the test material has an LD50 of >2000mg/kg bodyweight (hameln rds a.s., section of Biological Studies, 2014).

 

The potential acute dermal toxicity of the test material was evaluated in male rats in a study conducted according to a standard similar to the OECD Guideline for the Testing of Chemicals No. 402. It has been concluded that the test material has an LD50 of >5000mg/kg bodyweight (Huntingdon Life Sciences, 2005).

The potential acute inhalation toxicity of the test material was evaluated in a study of Klimish 4 reliability, The study confirms that the substance has not inhalatory toxicity effects on rats.

Justification for selection of acute toxicity – oral endpoint
GLP study conducted according to international guidelines.

Justification for selection of acute toxicity – dermal endpoint
Well documented study pre-dating OECD protocolls and GLP requirements. However, slight shortcomings regards documentation (e.g.number of animals, number of animals per dose ) justify a Klimisch 2 rating (reliable with restrictions).

Justification for classification or non-classification

Acute Toxicity, oral: the substance has an acute oral LD50 of greater 2000 mg/kg bw. As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.1.

 

Acute Toxicity, dermal: the substance has an acute dermal LD50 of greater 5000 mg/kg bw. As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.1.

Acute Toxicity, inhalation: there is no information available concerning inhalation toxicity; data is lacking.

A Klimish 4 study confirms that the substance has not inhalatory toxicity effects on rats.