N,N-diethyl-3-oxobutyramide

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

NOAEL was considered to be in the range of 90 to 1000 mg/kg bw when mice and rat were treated wtih N,N-Diethyl-3-oxobutyramide.

Thus, comparing this value with the criteria of CLP regulation N,N-Diethyl-3-oxobutyramide (CAS no 20306-75-6) is not likely to classify as repeated dose toxicant.

Repeated dose inhalation toxicity:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance N,N-Diethyl-3-oxobutyramide (CAS no 20306-75-6),which is reported as 0.01 mmHg at 25 C. Thus, exposure to inhalable dust, mist and vapour of the chemical 2-Undecanone is highly unlikely. Therefore this study is considered for waiver.

Repeated dose dermal toxicity:

In accordance with coloumn 2 of Annex IX, this end point was considered for waiver since the acute toxicity by the dermal route has already been provided in section 7.2.3 (as part of the Annex VIII information requirements)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data of read across substances

Justification for type of information:

Weight of evidence approach based on structurally similar chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

WoE report is based on two repeated dose toxicity studies 1.Repaeted dose oral toxicity study of test chemical in mice 2. Repaeted dose oral toxicity study of test chemical in rat

GLP compliance:

not specified

Limit test:

no

Species:

other: 1. mice, 2. rat

Strain:

other: 1. CD-1

Sex:

male/female

Route of administration:

oral: feed

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1. 90 days2. 10 days

Frequency of treatment:

Daily

Remarks:

1. 0, 300, 1000, 3000, 6000, and 10,000 mg/kg/day

Remarks:

2. ca. 90 or 940 mg/kg/d

No. of animals per sex per dose:

1. Total: 1800 mg/kg/day: 15 male, 15 female 300 mg/kg/day: 15 male, 15 female1000 mg/kg/day: 15 male, 15 female3000 mg/kg/day: 15 male, 15 female6000 mg/kg/day: 15 male, 15 female10,000 mg/kg/day: 15 male, 15 female

Control animals:

yes

Details on study design:

not specified

Positive control:

not specified

Observations and examinations performed and frequency:

1 CAGE SIDE OBSERVATIONS: Yes - Time schedule:- Cage side observations checked in table [No.?] were included.DETAILED CLINICAL OBSERVATIONS: Yes / No / No data- Time schedule:BODY WEIGHT: Yes - Time schedule for examinations:FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes - Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data2. DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule:BODY WEIGHT: Yes - Time schedule for examinations:FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes HAEMATOLOGY: Yes CLINICAL CHEMISTRY: Yes

Sacrifice and pathology:

1. and 2. GROSS PATHOLOGY: Yes HISTOPATHOLOGY: Yes

Other examinations:

not specified

Statistics:

not specified

Clinical signs:

no effects observed

Description (incidence and severity):

1. No treatment-related clinical signs were observed in treated mice.

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

1. When treated with 3000 mg/kg bw, decreased body weight gain were observed in animals

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

1. No treatment-related effects on food consumption were observed in treated mice.

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

1. When treated with 1000 mg/kg bw, increase Absolute and relative liver weights were observed in males and females mice. When treated with 300 mg/kg bw, increase Absolute and relative liver weights were observed in female mice. Increased liver weights and the corresponding hypertrophy were considered to be adaptive changes rather than an indication of systemic toxicity.2. When treated with 940 mg/kg bw, relative liver weight and relative and absolute kidney weights slightly increased n treated rats.

Gross pathological findings:

no effects observed

Description (incidence and severity):

1. No treatment-related effects on gross pathology were observed in treated mice.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

1. When treated with 3000 mg/kg bw, Multifocal hepatocellular hypertrophy was observed at high incidence in males and females mice. When treated with 1000 mg/kg bw, Multifocal hepatocellular hypertrophy was observed at a lower incidence in females mice. Hypertrophy was considered to be adaptive changes rather than an indication of systemic toxicity.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

90 - 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

food consumption and compound intake

gross pathology

histopathology: non-neoplastic

organ weights and organ / body weight ratios

Remarks on result:

other: No effect observed

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Conclusions:

NOAEL was considered to be in the range of 90 to 1000 mg/kg bw when mice and rat were treated wtih N,N-Diethyl-3-oxobutyramide.

Executive summary:

Data available for the read across chemicals was reviewed to determine the reproductive toxicity of N,N-Diethyl-3-oxobutyramide (CAS no. 2235-46-3). The studies are as mentioned below:

Study 1:

Repeated dose toxicity test were performed on CD-1 mice with test chemical in the concentration of 0, 300, 1000, 3000, 6000, and 10,000 mg/kg/day orally in diet for 90 days. No treatment-related clinical signs or effects on food consumption were observed in treated mice. Decreased body weight gain were observed in animals at 3000 mg/kg bw. Increase Absolute and relative liver weights were observed in males and females mice at 1000 mg/kg bw. Increase Absolute and relative liver weights were observed in female mice at 300 mg/kg bw. Increased liver weights were considered to be adaptive changes rather than an indication of systemic toxicity. In addition, No treatment-related effects on gross pathology were observed in treated mice. Multifocal hepatocellular hypertrophy was observed at high incidence in males and females mice at 3000 mg/kg bw. Multifocal hepatocellular hypertrophy was observed at a lower incidence in females mice at 1000 mg/kg bw. Hypertrophy was considered to be adaptive changes rather than an indication of systemic toxicity. Therefore, NOAEL was considered to be 1000 mg/kg bw when CD-1 male and female mice were treated with test chemical orally in diet for 90 days.

Study 2:

In repeated dose oral toxicity study, rats were treated with test chemical in the concentration of 90 or 940 mg/kg/d orally in diet for 10 days. Relative liver weight and relative and absolute kidney weights slightly increased in treated rats at 940 mg/kg bw. Therefore, NOAEL was considered to be 1000 mg/kg bw when CD-1 male and female mice were treated with test chemical orally in diet for 90 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

Data is Klimicsh 2 and from authoritative database

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Data available for the read across chemicals was reviewed to determine the reproductive toxicity of N,N-Diethyl-3-oxobutyramide (CAS no. 2235-46-3). The studies are as mentioned below:

Study 1:

Repeated dose toxicity test were performed on CD-1 mice with test chemical in the concentration of 0, 300, 1000, 3000, 6000, and 10,000 mg/kg/day orally in diet for 90 days. No treatment-related clinical signs or effects on food consumption were observed in treated mice. Decreased body weight gain were observed in animals at 3000 mg/kg bw. Increase Absolute and relative liver weights were observed in males and females mice at 1000 mg/kg bw. Increase Absolute and relative liver weights were observed in female mice at 300 mg/kg bw. Increased liver weights were considered to be adaptive changes rather than an indication of systemic toxicity. In addition, No treatment-related effects on gross pathology were observed in treated mice. Multifocal hepatocellular hypertrophy was observed at high incidence in males and females mice at 3000 mg/kg bw. Multifocal hepatocellular hypertrophy was observed at a lower incidence in females mice at 1000 mg/kg bw. Hypertrophy was considered to be adaptive changes rather than an indication of systemic toxicity. Therefore, NOAEL was considered to be 1000 mg/kg bw when CD-1 male and female mice were treated with test chemical orally in diet for 90 days.

Study 2:

In repeated dose oral toxicity study, rats were treated with test chemical in the concentration of 90 or 940 mg/kg/d orally in diet for 10 days. Relative liver weight and relative and absolute kidney weights slightly increased in treated rats at 940 mg/kg bw. Therefore, NOAEL was considered to be 1000 mg/kg bw when CD-1 male and female mice were treated with test chemical orally in diet for 90 days.

Thus, Based on the data available for the read across chemical, No Observed Adverse Effect Level (NOAEL) was considered to be above 90 -1000 mg/kg bw . Thus, comparing this value with the criteria of CLP regulation N,N-Diethyl-3-oxobutyramide (CAS no 20306-75-6) is not likely to classify as repeated dose toxicant.

Repeated dose inhalation toxicity:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance N,N-Diethyl-3-oxobutyramide (CAS no 20306-75-6),which is reported as 0.01 mmHg at 25 C. Thus, exposure to inhalable dust, mist and vapour of the chemical 2-Undecanone is highly unlikely. Therefore this study is considered for waiver.

Repeated dose dermal toxicity:

In accordance with coloumn 2 of Annex IX, this end point was considered for waiver since the acute toxicity by the dermal route has already been provided in section 7.2.3 (as part of the Annex VIII information requirements)

Justification for classification or non-classification

Based on the data available for the read across chemical and criteria of CLP regulation N,N-Diethyl-3-oxobutyramide (CAS no 20306-75-6) is not likely to classify as repeated dose oral, dermal and inhalation toxicant.