N,N-diethyl-3-oxobutyramide

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from Auotharized database

Data source

Reference

Reference Type:

other: Auotharized database

Title:

Repaeted dose oral toxicity study of test chemical

Author:

HSDB

Year:

2018

Bibliographic source:

Hazardous Substances Data Bank

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Repaeted dose oral toxicity study of test chemical in mice

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-diethyl-m-toluamide

EC Number:

205-149-7

EC Name:

N,N-diethyl-m-toluamide

Cas Number:

134-62-3

Molecular formula:

C12H17NO

IUPAC Name:

Diethyltoluamide

Details on test material:

- IUPAC Name: N,N-diethyl-m-toluamide- InChI: 1S/C12H17NO/c1-4-13(5-2)12(14)11-8-6-7-10(3)9-11/h6-9H,4-5H2,1-3H3- Smiles: c1(C(=O)N(CC)CC)cc(ccc1)C- Molecular formula :C12H17NO- Molecular weight :191.2723 g/mol- Substance type:Organic- Physical state:Liquid

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: Diet

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Test chemical was incorporated into the diet. DIET PREPARATION- Rate of preparation of diet (frequency):- Mixing appropriate amounts with (Type of food):- Storage temperature of food:VEHICLE- Justification for use and choice of vehicle (if other than water): diet - Concentration in vehicle: 0, 300, 1000, 3000, 6000, and 10,000 mg/kg/day

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

300 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

3 000 mg/kg bw/day (nominal)

Doses / concentrations 5

Dose / conc.:

6 000 mg/kg bw/day (nominal)

Doses / concentrations 6

Dose / conc.:

10 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

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

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes - Time schedule:No data- Cage side observations checked in table [No.?] were included.: No dataDETAILED CLINICAL OBSERVATIONS: No data- Time schedule:No dataBODY WEIGHT: Yes - Time schedule for examinations:No dataFOOD 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: No data- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes HISTOPATHOLOGY: Yes

Other examinations:

not specified

Statistics:

not specified

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

No treatment-related clinical signs were observed in treated mice

Mortality:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

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):

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):

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.

Gross pathological findings:

no effects observed

Description (incidence and severity):

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):

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

Details on results:

Due to rejection of the treated diets, the 6000 and 10,000 mg/kg/day dose groups were discontinued after two weeks.

Effect levels

Dose descriptor:

NOAEL

Effect level:

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

Target system / organ toxicity

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

Applicant's summary and conclusion

Conclusions:

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.

Executive summary:

In repeated dose oral toxicity study,CD-1 male and female mice were treated with test chemical in the concnetration 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.