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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23rd September 2014 - 14th October 2014
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Substance in 80% solution with propylene glycol in order to make the test feasable. The solvent is not thought to affect the results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction products of triethanolamine esters of polyphosphoric acids with alkyl derivatives of pyridine
EC Number:
939-981-3
IUPAC Name:
Reaction products of triethanolamine esters of polyphosphoric acids with alkyl derivatives of pyridine
Constituent 2
Reference substance name:
Propane-1,2-diol
EC Number:
200-338-0
EC Name:
Propane-1,2-diol
Cas Number:
57-55-6
IUPAC Name:
propylene glycol
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Date Recieved: 29th July 2013
- Expiration date of the lot/batch: Not Supplied

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark
- Stability under storage conditions: Stable
- Stability under test conditions: Stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 163-178g
- Fasting period before study: Overnight
- Housing: Animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to food was allowed throughout the study.
- Water (e.g. ad libitum): With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water was allowed throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C to 25°C
- Humidity (%): 30% to 70%
- Air changes (per hr): At least 15
- Photoperiod (hrs dark / hrs light): 12hours / 12 hours



Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Remarks:
For the purpose of the 2000 mg/kg dose level the test item was used as supplied.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation.
GLP Statement for exception: No analysis was carried out to determine the homogeneity, concentration or stability of the testitem formulation. The test item was formulated within two hours of it being applied to the testsystem; it is assumed that the formulation was stable for this duration. This exception isconsidered not to affect the purpose or integrity of the study.
Dimethyl sulphoxide was used because the test item did not dissolve/suspend in distilled water or arachis oil BP.

MAXIMUM DOSE VOLUME APPLIED: 2000mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Doses:
300mg/kg
2000mg/kg
No. of animals per sex per dose:
1 female rat at 300mg/kg
1 female rat at 2000mg/kg
4 further female rats at 2000mg/kg
Totalling 5 at 2000mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Weighing was done on days 0, 7 and 14.
- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: At the end of the observation period the animals were subjected to gross necropsy. This consisted of an external examination and opening of the
abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
N/A

Results and discussion

Preliminary study:
There was no mortality in the rat tested at 300mg/kg or at 2000mg/kg
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
other: Hunched posture was noted in all animals. Ataxia was also noted in the four additional treated animals and red/brown staining of the eyes was also noted in two of these animals.
Gross pathology:
No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute oral median lethal dose was estimated to be greater than 2000mg/kg body meight. The test item is therefore classed as category 5 (GHS).
Executive summary:

Introduction

The acute oral median lethal dose was assessed in female wistar rats.

Methods

The test was in line with the following guidelines:

  • OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" (2001)
  • Method Bl bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test item at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality - No deaths

Clinical observations - Hunched posture was noted in all animals. Red/brown staining of the eyes and/or ataxia was also noted in the four additional treated animals. Animals appeared normal I or 2 days after dosing.

Body weight - All animals showed expected gains in body weight

Necropsy - no abnormalities were noted at necropsy

Conclusion

The acute oral median lethal dose (LDso) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Category 5).