2-Propenamide, N-[4-[[(4,6-dimethyl-2-pyrimidinyl)amino]sulfonyl]phenyl]-2-methyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2002

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: "Acute Oral Toxicity - Acute Toxic Class method" JMAFF Guidelines

Version / remarks:

2000, inclusing the most recent partial revisions

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

N-{4-[(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenyl}-2-methylprop-2-enamide

EC Number:

611-915-5

Cas Number:

59941-98-9

Molecular formula:

C16 H18 N4 O3 S

IUPAC Name:

N-{4-[(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenyl}-2-methylprop-2-enamide

Test material form:

solid: particulate/powder

Remarks:

determined at NOTOX

Details on test material:

pH 6.4 (determined at NOTOX)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Age and body weight: Young adult animals (approx. 11 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark.
Health inspection A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of
health.

Conditions
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +- 3.0°C (actual range: 20.7-22.4°C), a relative humidity of 30-70% (actual range: 34% - 61%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Accommodation
Group housing of 3 animals per cage in labelled lvlacrolon cages (MIV type; height 18 cm.) containing sterilised sawdust as bedding material (Woody-Clean type 3/4, Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BlVll BV, Someren, The Netherlands).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet
Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage,
Germany).

Water
Free access to tap water.
Results of analysis for each batch of diet (nutrients) and results of quarterly analysis of diet (contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

Source: Genfarma, Zaandam, The Netherlands

Details on oral exposure:

Use of stainless steel stomach tube
Food was witheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of test substance

Doses:

Single dosage of 2000 mg/kg bodyweight (10 ml/kg) on day 1

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no

Clinical signs:

other: Hunched posture was noted among the majority of animals between days 1 and 3.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals,

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of v123109 in Wistar rats was established to exceed 2000 mg/kg body weight,

Based on these results v123109 does not have to be classified and has no obligatory labelling requirement for oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (New York and Geneva, 2003) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC)"