Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
92/69/EEC
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
A mixture of: triphenylthiophosphate and tertiary butylated phenyl derivatives
EC Number:
421-820-9
EC Name:
A mixture of: triphenylthiophosphate and tertiary butylated phenyl derivatives
Cas Number:
192268-65-8
Molecular formula:
Unspecified
IUPAC Name:
A mixture of: triphenylthiophosphate and tertiary butylated phenyl derivatives
Details on test material:
- Appearance: yellowish liquid.
- Storage condition of test material: Room temperature in dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Further characterisation: Hsd/ola:Sprague- Dawley(CD).
- Source: Harlan Olac Ltd, Bicester, Oxon, England.
- Age at study initiation: Approximately four to seven weeks of age.
- Weightrange at study initiation: 83 to 100 g.
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
- Housing: 5 rats/sex in metal cages with wire mesh floors.
- Diet: ad libitum; standard laboratory diet (SDS LAD 1); analysed for nutrients, and possible contaminants).
- Water: ad libitum (water was examined weekly for contaminants)
- Acclimation period: five days prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C.
- Humidity (%): 30-70%.
- Air changes (per hr): 10 to 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12/ 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
None
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.7 mL/kg body weight.
Doses:
2.0 g/kg body weight.
No. of animals per sex per dose:
5/sex.
Control animals:
no
Details on study design:
- Rationale for choice of species: The rat was chosen as it has been shown to be a suitable model for this type of study and is the animal recommended in the test guideline
- Duration of observation period following administration: 14 days.
- Mortality: Cages of rats were checked at least twice daily for any mortalities.
- Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of approximately five hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity of the clinical signs and time were recorded at each observation.
- Bodyweight: recorded individually on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: Yes (All animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities.

Statistics:
Not required (acute test).

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No death occurred
Clinical signs:
Piloerection was observed in all test animals within seven minutes of dosing, throughout the remaining of day one and persisted over the following four days. Recovery, as judged by external appearance and behaviour, was complete in all instances by Day 6. No other clinical signs were observed.
Body weight:
Slight low body weight gain was recorded for one male on day eight and day fifteen. Body weight gain of the remaining animals was normal
Gross pathology:
Macroscopic examination at necropsy revealed no abnormalities.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute lethal oral dose to rats of the test item was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

A GLP-compliant study was performed to assess the acute oral toxicity of the test item to the rat. The method followed was that described in EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.l. Acute toxicity (oral). A group often fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, as supplied, at a dose level of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There were no deaths. Clinical signs of reaction to treatment were confined to piloerection, seen in all rats. Recovery was complete in all instances by Day 6. A slighdy low bodyweight gain was recorded for one male on both Day 8 and Day 15, all other rats achieved satisfactory bodyweight gains throughout the study. Macroscopic examination on Day 15 revealed no abnormalities. The acute lethal oral dose to rats of the test article was found to be greater than 2.0 g/kg bodyweight.