Oxazolidine, diheptyl~

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb. 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

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:

2004

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

EPA 712-C-98-190, 2002

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMALS
- Species: Rat, Wistar strain Crl:WI (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC).
- Number of animals: 3 males or 3 females per group (females were nulliparous and nonpregnant).
- Age and body weight: Young adult animals (approx. 8 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.

HUSBANDRY
- 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: 21.2 - 22. 7°C), a relative humidity of 30-70% (actual range: 41- 65%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
- Accommodation: Group housing of 3 animals per cage in labelled Macrolon cages (MIV type; height 18 cm.) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ud), Surrey, United Kingdom). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, 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:

unchanged (no vehicle)

Details on oral exposure:

- Method: Oral gavage, using plastic feeding tubes.
- Fasting: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
- Frequency: Single dosage, on Day 1.
- Dose level (volume): 2000 mg/kg (2.174 mL/kg) body weight Dose (volume calculated as dose level: density).

Doses:

2000 mg/kg bw

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 and 3 males. 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.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture was noted in all animals on Day 1.

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 the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results the test substance 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).

Executive summary:

Assessment of acute oral toxicity with the test substance in the rat (Acute Toxic Class Method)

The study was carried out based on the guidelines described in:

OECD No. 423 (2001) "Acute Toxicity-Oral, Acute Toxic Class Method"

EC, Council Directive 67/548/EEC, Annex V, B.1 tris (2004) "Acute Oral Toxicity"

EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity - Acute Toxic Class Method"

JMAFF guidelines (2000) including the most recent partial revisions.

The test substance was administered by oral gavage to three female Wistar rats and subsequently to three male Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Hunched posture was noted in all animals on Day 1.

The body weight gain shown by the animals over the study period was considered to be normal.

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

The oral LD50 value of SAT 060283 in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results the test substance 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).