Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Yellowish liquid; molar mass: 298.4 g/mol; purity: 95.0 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, Borchen, Germany
- Strain: HsdCpb:Wu
- Age at study initiation: 10 - 12 weeks
- Weight at study initiation: 162 -207 g
- Fasting period before study: 16 - 24 hours
- Housing: in groups
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 2
- Humidity (%): 55 +- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: demineralized water
Doses:
300, 2000 mg/kg
No. of animals per sex per dose:
6 (300 mg/kg), 3 (2000 mg/kg)
Control animals:
no
Details on study design:
- Application volume: 10 ml/kg bw
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once daily (clinical signs, mortality) or once weekly (weight gain)
- Necropsy of survivors performed: yes
Statistics:
Not specified.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
other: LD50 cut-off
Effect level:
500 mg/kg bw
Mortality:
All animals dosed with 2000 mg/kg died within the first hour after administration. A dose of 300 mg/kg was tolerated by female rats without mortalities.

Clinical signs:
All animals dosed with 2000 mg/kg showed decreased motility, spasmodic state, increased salvation, abdominal position and labored breathing. In animals of the dose group 300 mg/kg increased salvation, decreased motility, piloerection and narrowed palpebral fissure were observed up to 4 hours after administration.
Body weight:
A dose of 300 mg/kg was tolerated by female rats without effects on body weight gain.
Gross pathology:
At 2000 mg/kg the gross pathology investigations revealed: liver brownish-black, spleen brownish-black and kidneys spotted clay-colored. No gross pathological findings were observed in animals of the dose group 300 mg/kg.


Without effect on weight gain and gross pathological findings.
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

According to OECD guideline 423 the LD50 cut-off of Tetrabutylphosphoniumhydrogendifluorid is 500 mg/kg bw for rats (Category 4 of the Globally Harmonized Classification System).