N,N-dimethyl-3-oxobutyramide

Endpoint summary

Description of key information

Oral toxicity:
------------
In the oral toxicity study no animals died during the observation period. No clinical signs were observed during the fourteen days. 
Therefore, the LD50 of the test item is > 5000 mg/kg bw.
Inhalation toxicity:
-----------------
The acute inhalation study was waived taking in to account the vapour pressure and the aggregate state of the substance (liquid). The second likely route of human exposure is by dermal route. Therefore a dermal study was performed. 
Dermal toxicity:
--------------      
No death occurred in a dermal toxicity study after the single 2000 mg/kg bw dermal dose of LZ705. There were no systemic toxic clinical signs in both sexes and no any related effect of the test item found in body weights and body weight gains of animals during the study. Autopsy revealed no treatment related pathological changes. Under the experimental conditions, the acute dermal LD50 value of the test item LZ705 was determined to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable for reliability but not in detail documented. Study report meets basic scientific principles. Study was conducted prior to GLP and OECD guideline implementation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Litchfield and Wilcoxan method.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Rats:
----
Female Wistar rats weighing 200 +- 20 g. These animals were housed in grid-floor cages under natural lighting conditions with the ambient temperature maintained at 22°C.
Mice:
----
Tylers original strain weighing 20 +- 2 g. These animals were housed in solid floor polycarbonate boxes under natural lighting conditions and maintained at 22°C.
Rabbits:
-------
New Zealand White does weighing 2.0 +- 0.2 kg. All animals were caged individually under natural lighting conditions maintained at 22°C.

Route of administration:

oral: gavage

Vehicle:

other: distilled water and 0.5% aqueous solution of Tween 80

Details on oral exposure:

Groups of animals were observed for a period of one week and the signs of toxicity and total deaths in each group noted.

Doses:

Range-finding:
--------------
solid material: 5000 mg/kg, 2500 mg/kg, 1000 mg/kg and 500 mg/kg
liquid samples: 5.0 mL/kg, 2.5 mL/kg, 1.0 mL/kg and 0.5 mL/kg
LD 50 Determination:
-------------------
Mouse: 5 mL/kg

No. of animals per sex per dose:

Range -finding:
--------------
Rats, Rabbits and Mice: Two animals per dose
LD 50 Mouse:
------------
Ten animals (5 male and 5 female mice)

Control animals:

no

Details on study design:

All animals were fasted overnight prior to administration and provided their normal food and water subsequent to dosing. All materials were administered by gavage using metal cannulae for mice and rats and a rubber stomach catheter for rabbits.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks:

suspended in 10% aqueous solution

Mortality:

No mortality observed.

Clinical signs:

other: No signs of toxicity or clinical signs observed.

Gross pathology:

No information available.

Other findings:

No other findings were detected.

Tylers Mice and New Zealand White Rabbits were also used in the LD50 investigation. No animals died during the observation period. No clinical signs were observed during the fourteen days.

Therefore, the LD50 of the test item for Mice is > 5 mL/kg bw at a dosing concentration of 10% aqueous solution and the LD50 for Rabbits is > 5 mL/kg bw (test item undiluted).

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No animals died during the observation period. No clinical signs were observed during the fourteen days.
Therefore, the LD50 of the test item is > 5000 mg/kg bw.

Executive summary:

The study was conducted prior to GLP and OECD guideline implementation.

Acceptable for reliability but not in detail documented. Nevertheless, the study report meets basic scientific principles.

This study was undertaken to determine the oral median lethal dose (LD50) of test article LZ705 in Wistar rats. The study was performed during August 1973.

No animals died during the observation period. No clinical signs were observed during the fourteen days.

Therefore, the LD50 of the test item is > 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study conducted in accordance with international guidelines.

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: Crl: (WI) BR rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
Species / Strain: Crl:(WI)BR rats
Hygienic level: SPF at arrival and kept in a good conventional environment during the study
Number of animals (preliminary study): 2 animals/dose
Number of animals (main study): 5 animals/dose
Age of animals: Young adult rats, females were nulliparous and non-pregnant
Sex: female and male
Body weight range in preliminary study at starting: 218 - 246 g
Body weight range in main study at starting (male): 243 - 290 g
Body weight range in main study at starting (female): 212 - 228 g
Acclimatization time: 5 days in preliminary study, 20 days in main study

HOUSING CONDITIONS:
Animal health: Only healthy animals were used for the study. The health status was certified by the breeder.
Number of animal room: IV (E building)
Housing: during acclimatization: 3 animals/sex/cage
During the study: animals were housed individually.
Cage type: Type II polypropylene/polycarbonate; rat type cages with a solid floor, stainless steel wire covers and self-feeding baskets.

ENVIRONMENTAL CONDITIONS:
Illumination: Artificial light, from 6 a.m. to 6 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: 8-12 air exchanges/hour by central air-condition system.

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

aqua purificata

Details on dermal exposure:

The back of animals was shaven (approximately 10 % area of the total body surface) 24 hours prior to the treatment. The test item was applied in a single 2000 mg/kg bw dose uniformly over the shaved skin throughout a 24- hour exposure period. Sterile gauze pads were placed on the skin of rats. These gauzes were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was wrapped with semi occlusive plastic wrap for 24 hours.
At the end of the exposure period, residual test item was removed, using body temperature water.

Duration of exposure:

24 hours

Doses:

Preliminary study: 5 mg/kg bw, 50 mg/kg bw, 300 mg/kg bw and 2000 mg/kg bw
Main study: 2000 mg/kg bodyweight.

No. of animals per sex per dose:

Preliminary study: 2 Females per dose
Main study: 5 Males and 5 Females.

Control animals:

not required

Details on study design:

The test item was applied in original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.
The test item was not expected to be lethal at 2000 mg/kg bw on the basis of result of preliminary study.
A limit test was performed.
The test substance was moistened sufficiently with water to ensure good contact with the skin.
Mortality: Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day.
Clinical observations: Careful clinical observation was made at the following intervals: 1h, 5h after the treatment and once each day for 14 days thereafter.
Body weight: The body weight was recorded on day 0 (shortly before the treatment) in preliminary study and on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g in main study.
Pathology: At the end of the observation period all rats of main study were sacrificed under isofluran anaesthesia.

Preliminary study:

There were no deaths in preliminary study at 5, 50, 300 and 2000 mg/kg bw dose levels.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred after the 24-hour dermal exposure to LZ705 in male and female rats during the study.

Clinical signs:

other: No behavioural changes or systemic toxic signs were noted during the study.

Gross pathology:

All animals survived until the scheduled necropsy on Day 15.
Slight hydrometra was found in two animals (No.: 5461, 5471). The hydrometra is physiological finding and connected to the cycle of the animal. No macroscopic alterations due to the systemic toxic effects of the test item were found.

Other findings:

No other findings.

Dermal irritation symptom as erythema and other sign as wound were observed on the treatment site. The very slight redness (score +1) appeared in all males and was detectable between Day 1 and Day 2. This very slight symptom (score +1) was observed in four females (No.: 5461, 5462, 5463, 5472) and was detectable between Day 1 and Day 2. Wound was recorded in three males (No.: 5396, 5397, 5398) between Day 2 and Day 7.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions, the acute dermal LD50 value of the test item LZ705 was determined to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Executive summary:

The acute dermal toxicity study was performed in year 2012 in accordance with international guidelines and GLP. No death occurred after the single 2000 mg/kg bw dermal dose of LZ705. There were no systemic toxic clinical signs at both sexes and no any related effect of the test item found in body weights and body weight gains of animals during the study. Autopsy revealed no treatment related pathological changes. Under the experimental conditions, the acute dermal LD50 value of the test item LZ705 was determined to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral toxicity:

An oral toxicity study was conducted prior to GLP and OECD guideline implementation. Acceptable for reliability but not in detail documented. Nevertheless, the study report meets basic scientific principles. This study was undertaken to determine the oral median lethal dose (LD50) of test article LZ705 in Wistar rats. The study was performed during August 1973.

Inhalation toxicity:

In accordance with column 2 of Annex VIII (required in Section 8.5.2) of REACH Regulation 1907/2006 testing by the inhalation route is appropriate if exposure of humans is likely taking in to account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. The calculated vapour pressure of LZ705 is 1984 Pa at 25°C and no particle size distribution study was performed as the substance is a liquid. Furthermore, the second likely route of human exposure is by dermal route. Therefore a dermal study was performed. On this basis an acute inhalation study is not required.

Dermal toxicity:

A acute dermal toxicity study was performed in year 2012 in accordance with international guidelines and GLP. No death occurred after the single 2000 mg/kg bw dermal dose of LZ705. There were no systemic toxic clinical signs at both sexes and no any related effect of the test item found in body weights and body weight gains of animals during the study. Autopsy revealed no treatment related pathological changes.

Justification for selection of acute toxicity – oral endpoint
The study was conducted prior to GLP and OECD guideline implementation.
Acceptable for reliability but not in detail documented. Nevertheless, the study report meets basic scientific principles.

Justification for selection of acute toxicity – dermal endpoint
GLP compliant study conducted in accordance with international guidelines. Reliable study without restrictions.

Justification for classification or non-classification

Based on the data available the substance is not classified according to Regulation 1272/2008/EEC (CLP) and according to Directive 67/548/EEC (DSD).