Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 June - 01 July 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to internationally accepted guidelines and to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry ofAgriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nohsan No 8147, Agricultural Production Bureau, November 24, 2000.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diisoamyl phthalate

- Substance type: organic
- Physical state: colourless to yellow liquid
- Analytical purity: 99.98%


- Lot/batch No.: 7920-1-1
- Expiration date of the lot/batch:12 August 2012

- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 201 to 225 g
- Fasting period before study: yes, overnight prior to and approximately four hours after dosing.
- Housing: They were housed in groups of three rats of the same sex, in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding.
- Diet (e.g. ad libitum): Rat and Mouse No.1 Maintenance Diet ad libitum
- Water (e.g. ad libitum): ad libitum from public supply
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23
- Humidity (%): 40 to 70
- Air changes (per hr): not reported, the animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 08 June 2010 To: 01 July 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle (corn oil): 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Regulatory accepted standard choice

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As some previous toxicological information indicated that the test material should not be toxic the
initial dose level was 2000 mg/kg.
Doses:
300 and 2000mg/kg
No. of animals per sex per dose:
3 female rats per dose group (4 groups in total, 2 dosed at 300 mg/kg and 2 dosed at 2000 mg/kg)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Day 1 frequent intervals, 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).
- Weight: recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: All rats humanely killed on day 15 for macroscopic examination.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
Statistics:
None

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
Clinical signs of reaction to treatment comprised salivation, seen in one female dosed at 2000 mg/kg. This sign was first noted immediately after dosing. Recovery of the animal, as judged by external appearance and behaviour, was complete by one hour after dosing on Day 1. No clinical signs were seen in any animal dosed at 300 mg/kg or remaining animals dosed at 2000 mg/kg.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination at study termination on Day 15 revealed a small (atrophy) of the stomach in two animals treated at 2000 mg/kg. No abnormalities were revealed in any other animal at the macroscopic examination at this time.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information: or unclassified (in CLP)
Conclusions:
The acute median lethal oral dose (LD50) to rats of Diisoamyl phthalate was demonstrated to be greater than 2000 mg/kg bodyweight.
Executive summary:

The study was performed to assess the acute oral toxicity of Diisoamyl phthalate (for use in the manufacturing of propellants), to the rat.

Two groups of three fasted female rats received a single oral gavage dose of the test substance, formulated in corn oil, at a dose level of 300 mg/kg bodyweight. As results at this dose level indicated the acute (median) lethal oral dose of the test substance to be greater than 300 mg/kg bodyweight, in compliance with the study guidelines a further two groups of three fasted females were similarly dosed at 2000 mg/kg bodyweight to complete the study.

There were no deaths during the study. Clinical signs of reaction to treatment comprised salivation, seen in one female dosed at 2000 mg/kg. This sign was first noted immediately after dosing. Recovery of the animal, as judged by external appearance and behaviour, was complete by one hour after dosing on Day 1. No clinical signs were seen in any animal dosed at 300 mg/kg or the remaining animals dosed at 2000 mg/kg.

All animals were considered to have achieved satisfactory bodyweight gains throughout the study.

Macroscopic examination at study termination on Day 15 revealed a small (atrophy) of the stomach in two animals treated at 2000 mg/kg. No abnormalities were revealed in any other animal at the macroscopic examination at this time.

The acute median lethal oral dose (LD50) to rats of Diisoamyl phthalate was demonstrated to be greater than 2000 mg/kg bodyweight.

Diisoamyl phthalate is included in Category 5 or unclassified, according to the Globally Harmonised System (GHS), (UNITED NATIONS, 2005).