Hexahydro-4-methylphthalic anhydride

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexahydro-4-methylphthalic anhydride

EC Number:

243-072-0

EC Name:

Hexahydro-4-methylphthalic anhydride

Cas Number:

19438-60-9

Molecular formula:

C9H12O3

IUPAC Name:

5-methyl-octahydro-2-benzofuran-1,3-dione

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 or test system 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:

other: 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 muzzl

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.