Tributyl-2-methoxypropylphosphonium salt with 4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]bis[phenol]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 June 2005 to 5 August 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted under GLP conditions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAPP guidelines (2000) including the most recent partial revisions.

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

MTDID 3285

IUPAC Name:

MTDID 3285

Details on test material:

- Name of test material (as cited in study report: MTDID 3285
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type: light brwon waxy chunks
- Physical state: solid
- Analytical purity: minimum 86%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers compositon:
- Purity test date:
- Lot/batch no.: Lot 30045
- Expiration date of the lot/batch: 01 June 2006
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark
- Other: Molecular weight: 610. pH: 9.8 (in 1% water). Stability in vehicle (propylene glycol): unknown.
Solubility in vehicle: No

Test animals

Species:

rat

Strain:

other: Wistar strain Crl:WI (outbred, SPF-Quality)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 9 weeks old
- Weight at study initiation: 186 to 223 grams
- Fasting period before study: overnight (maximum of 20 hours) prior to dose until 3-4 hours after administration of test article.
- Housing:- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3-23 degrees C
- Humidity (%): 35-87% (above optimal humidity, but not expected to affect study integrity.
- Air changes (per hr): 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light/ 12 hours dark
IN-LIFE DATES: From: 02 June 2005 To: 17 June 2005

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
- maximum dose volume applied: 2000 mg/kg (10 ml/kg) body weight

Doses:

2000 mg/kg (10 ml/kg) body weight

No. of animals per sex per dose:

3 animals/per sex/per dose (all groups received same dose level)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily observations for mortality/viability. Body weights were observed on Days 1, 8 and 15. Clinical signs were observed at periodic intervals on the day of dosing and once daily until day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other

Statistics:

No statistical analysis was performed, method not intended to develop a precise LD50.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: OECD GHS and and EC criteria for classification and labeling requirements for dangerous substances and preparations.

Conclusions:

The oral LD50 value of the test article 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 m/kg body weight. Based on these results, the test article 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 of the United Nations and EC criteria for classification and labeling requirements for dangerous substances and preparations.

Executive summary:

The acute oral toxicity of the test article was assessed in the rat using the Acute Toxic Class Method. The study followed guidelines from the OECD, no. 423, EC Council Directive 67/548/EEC, EPA OPPTS 870.1100 (2002) and JMAFF guidelines (2000) including the most recent partial revisions. The test article was administered by oral gavage to two subsequent groups of three female 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 occured in this study. Hunched posture was noted in one animal on day 1. No clinical signs were noted in the other animals. The mean 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 the test article 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 m/kg body weight. Based on these results, the test article 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 of the United Nations and EC criteria for classification and labeling requirements for dangerous substances and preparations.