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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:
2002-08-20 through 2002-09-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliance without deviations

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): PET-3-MP
- Physical state: liquid
- Analytical purity: 97.3%
- Purity test date: 2002-06-24
- Lot/batch No.: 2518
- Expiration date of the lot/batch: no data
- Stability under test conditions: guaranteed by the sponsor
- Storage condition of test material: approximately 4°C in the dark, under nitrogen

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bantin & Kingman, Hull, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 167-215 g
- Fasting period before study: yes
- Housing: in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


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


IN-LIFE DATES: From: 2002-08-20 To: 2002-09-02

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30, 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve in distilled water.
- Purity: BP grade

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Information from the sponsor suggested a starting dose of 300 mg/kg.
Doses:
300, 2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity %, 1, 2 and 4 hours after dosing
and subsequently once daily for up to fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
not applicable for ATC method

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
Remarks on result:
other: Estimated using the ATC flowchart
Mortality:
Two animals treated with 2000 mg/kg were found dead four hours or two days after dosing. One animal treated with 2000 mg/kg was killed in extremis one day after dosing. There were no deaths noted in animals treated with 300 mg/kg.
Clinical signs:
Signs of systemic toxicity noted in animals treated with 2000 mg/kg were hunched posture, increased lachrymation, clonic andlor tonic convulsions, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, loss of righting reflex, ataxia and hypothermia.
One animal treated with 2000 mg/mg was found comatose. Signs of systemic toxicity noted in animals treated with 300 mg/kg were hunched posture, increased lachrymation, clonic and/or tonic convulsions and pilo-erection. There were no signs of systemic toxicity noted in three animals treated with 300 mg/kg.
Body weight:
The surviving animals showed expected gains in bodyweight over the study period.
Gross pathology:
Abnormalities noted at necropsy of animals that died or were killed in extremis during the study were abnormally red lungs, dark liver, slight haemorrhage or sloughing of the gastric mucosa and slight haemorrhage of the non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Xn, R22 Criteria used for interpretation of results: EU
Conclusions:
EU classification: Xn, R22: Harmful if swallowed.
EU-GHS classification: Warning, Acute Tox. 4, H302: Harmful if swallowed.