Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From September 9, 2009 to October 2, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well described GLP compliant study conducted to recognized international test guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
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 :Hexahydro-4 Methylphthalic Anhydride
- Alternative name:4-MHHPA
- Physical state:viscous clear colourless liquid
- Purity: 99.70%
- Impurities (identity and concentrations): no data
- Lot/batch No.:T408209/159
- Expiration date of the lot/batch:june 2010
- Storage reference number:11830
- Storage in RTC:From arrival of RTC on 22 June 2009 to 3 August 2009 at ambient temperature; humidity <65%.
From 4 August 2009 at ambient temperature in a desiccator

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l
- Breeder: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Age at study initiation: 6/7 week old
- Weight at study initiation: 150-174 grams
- Housing: cage in Polycarbonate measuring 59x38.5x20 cm, with stainless steel mesh lid and floor
- Cage tray control: Daily inspected and changed as necessary (at least 3 times/week)
- Diet :ad libitum , (4 RF 18)
- Water :ad libitum
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22°C +/-2
- Humidity (%):55% +/- 15%
- Air changes (per hr):15 to 25
- Photoperiod (hrs dark / hrs light):artificial (Fluorescent tubes) cycle dark/light 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle:200 mg/ml
- Amount of vehicle (if gavage):10 ml/kg of body weight

Doses:
2000 mg/kg
No. of animals per sex per dose:
2 groups of animals: 3 females per dose per group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days, Termination Day 15.
- Frequency of observations and weighing:Observations - Daily; Weighing - Allocation (Day-1), Days 1, 2, 8 and 15.
- Terminal observations: Necropsy was carried out on all animals, (gross necropsy examination for both external and internal abnormalities, with particular attention to the gastro-intestinal tract). All abnormalities were recorded.

In life observations
- Mortality and morbidity:Twice daily.
- Clinical signs : Day of dosing (on dosing, approximately 0.5, 2 and 4 hours after dosing).
- Euthanasia method:Carbon dioxide narcosis.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed .
Clinical signs:
Hunched posture and piloerection were seen in 3 animals on Days 2 and 3. Recovery occurred by Day 4. Brown staining around the left eye was noted in a single animal from Day 12 up to the end of the observation period (Day 15) and red staining on the muzzle was observed in one animal on Day 2 only
Body weight:
Changes in body weight gain observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
No abnormalities observed

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute toxicity of Hexahydro-4 Methylphthalic Anhydride was investigated following a single oral administration to rats. No mortality occurred and no significant clinical signs were observed in the 6 animals following dosing at 2000 mg/kg.
These results indicate that the substance has no toxic effect on the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg body weight.

European Directives concerning the classification, packaging and labelling of dangerous substances and mixtures (Regulation (EC) Nos. 1907/2006, 1272/2008 and subsequent revisions) would indicate the following:

Classification : Not required
Signal word : None indicated
Hazard statement None indicated
Executive summary:

Acute oral toxicity following a single oral administration has been investigated in the rat in accordance with OECD/EU test methods. No mortality or significant clinical signs occurred indicating that 4-MHHPA has no toxic effect on the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg body weight.