2',4'-dimethylacetoacetanilide

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well performed OECD and GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2',4'-dimethylacetoacetanilide

EC Number:

202-576-0

EC Name:

2',4'-dimethylacetoacetanilide

Cas Number:

97-36-9

Molecular formula:

C12H15NO2

IUPAC Name:

2',4'-dimethylacetoacetanilide

Details on test material:

- Name of test material (as cited in study report): Acetessig-m-Xylidid TF

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Hoechst AG, Kastengrund, SPF-breed
- Strain: Hoe: WISKf(SPF71)
- Age at start of study: approx. 6 weeks
- Housing: in air conditioned rooms in groups of 5
- Temperature: 22 +/- 3°C
- Rel. humidity: 50 +/- 20 %
- Artificial light: 12 hours daily
- Acclimatisation: min 5 days
- Diet: Altromin 1324 - rat diet, ad libitum, except when animals were housed in metabolism cage
- Water: tap water from plastic feeders, except when animals were housed in metabolism cage
- Labelling: Animals: numbered earmarks, Cages: numbered labels
- Randomization: yes

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: starch mash 2%

Details on oral exposure:

- Preparation of doses: daily, just before application
- Time of day of application: between 9.30 am and 12.00 am

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 applications in 29 days (7 times a week)

Frequency of treatment:

once a day

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 8, 40, 200 mg/kg bw / day
Basis:
other: nominal

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

- General health status and behaviour twice a day during the week. During public holidays and weekends once a day
- Neurological status once a week
- Eyes, muscous membranes, dental status once a week
- Body weight: once immediately before start of the study, during the study twice a week
- Food consumption: twice a week
- Water consumption: once a week
- At the end of the study: hematology, clinical chemistry as well as urinalysis, organ weight, gross pathology, histological examination

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

parametric method by Dunnett, distributed-free methd by Nemenyi/Dunnett, two-sided T-test, two-sided Wilcoxen-test

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

no effects observed

Ophthalmological findings:

no effects observed

Description (incidence and severity):

no macroscopic abnormalities

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

200 mg/kg group, male: decreased red blood cell count, hemoglobin, and hematocrit

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

200 mg/kg group male and female: increased absolute and relative liver weight

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

200 mg/kg group male and female: pale kidneys

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOEL

Effect level:

40 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Behaviour, common health state, food and water consumption and body weight gain were unaffected by the test substance.

 

200 mg/kg bw:

 

Haematology: Slight decrease of erythrocyte count, haemoglobin, and haematocrit

 

Dose (mg/kg bw)	Erythrocytes (10E12/L)		Haemoglobin (g/l)		Heinz bodies
	male	female	male	female	male	female
Control	7.76	7.37	152	143	0.0	0.0
8.0	7.59	7.40	146	147	Not detected	Not detected
40.0	7.76	7.23	150	144	Not detected	Not detected
200.0	6.93	7.03	133	138	0.0	0.0

 

Clinical chemistry and urinalysis values were unaffected by the test substance.

Organ weight: Increased liver weight.

Gross pathology: Pale kidney

Histopathology: No abnormal findings

 

MetHb: No definite indications for MetHb formation reported. MetHb concentration not examined.

Applicant's summary and conclusion

Conclusions:

NOEL: 40 mg/kg bw

Executive summary:

The test substance was tested for subacute oral toxicity in rats according to OECD 407. Following this guideline, doses of 0, 8, 40 or 200 mg/kg bw per day were administered. Examinations were done as follows: behaviour, general state of health, body weight, food and water consumption, hematology, clinical chemistry, urinalysis, gross pathology, absolute and relative organ weights, histopathology. Treatment related effects were seen as follows: 200 mg/kg group, male: decreased red blood cell count, hemoglobin, and hematocrit, male and female: increased absolute and relative liver weight, pale kidneys. No other substance related effects were observed. Based on these findings a NOEL of 40 mg/kg bw was derived.