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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1995-11-28 to 1997-06-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1997
Reference Type:
study report
Title:
Unnamed
Year:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): tetrahydromethyl-1,3-isobenzofuranedione
- Analytical purity: 99.7%
- Lot/batch No.: 2522
- Stability under test conditions: stable
- Storage condition of test material: room temperature, dark place
- Molecular formula (if other than submission substance): C9 H10 O3
- Molecular weight (if other than submission substance): 166.18
- Smiles notation (if other than submission substance): O=C(OC(=O)C1CC=C(C2)C)C12
- InChl (if other than submission substance): 1/C9H10O3/c1-5-2-3-6-7(4-5)9(11)12-8(6)10/h2,6-7H,3-4H2,1H3
- Structural formula attached as image file (if other than submission substance): see Fig. (11070-44-3 structure.png)

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles river Japan
- Age at study initiation: purchase at 5 weeks old. Study is initiate at 6 weeks old
- Weight at study initiation: male 172.1-193.1g, female 125.4-139.9g
- Fasting period before study: from 17:00 on before day to after 3hr on dosing
- Housing:2-3 animals in polycarbonate cage with wood tip
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26°C
- Humidity (%): 45-65%
- Air changes (per hr): 13 times/hr
- Photoperiod (hrs dark / hrs light): 12/12 AM07:00-PM07:00

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: corn oil (10ml/kg)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5, 10 and 20 w/v% in vehicle
- Amount of vehicle (if gavage):10mL/kg
- Justification for choice of vehicle: Corn oil is generally used
- Lot/batch no. (if required): V5P5523 Nakalai Tesque

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: From results of prestudy (500, 1000 and 2000mg/kg p.o.). All animals did not die. at 2000mg/kg the body weight is decreased.
Doses:
0(Vehicle), 500, 1000 and 2000 mg/kg/day (in corn oil)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: more than one time/day. weighing: day 0, 2, 4, 6, 8, 11 and 15.
- Necropsy of survivors performed: (yes)/no
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: histopathology: In representative case,
histopathology observation was performed on stomach.
Statistics:
average and standard deviation (weight, per group)

Results and discussion

Preliminary study:
From results of prestudy (500, 1000 and 2000mg/kg p.o.). All animals did not die. at 2000mg/kg the body weight is decreased.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths prior to schedule termination.
Clinical signs:
Hypoactivity, bradypnea and prone position were observed in males and females of the 2000 mg/kg group on the day of administration.
Body weight:
The body weight of treatment groups of rats for males and females were not different from controls except in males and females of the 2000 mg/kg group was decreased at the day after administration.
Gross pathology:
At necropsy, thickening of the forestomach mucosa was observed in males and females of the 1000 and 2000 mg/kg group.
Adhesion of forestomach and liver was noted in one female of the 2000 mg/kg group.
Other findings:
Histopathology:
Squamous hyperplasia and granulomatous inflammation in submucosa of the forestomach were observed, and a squamous hyperplasia was also noted.
Squamous hyperplasia of the forestomach
1000mg/kg : male (2/5), female (1/5)
2000mg/kg : male (5/5), female (5/5)
(Squamous hyperplasia and granulomatous inflammation was observed in representative case of in males and females of the 1000 and 2000mg/kg group)
Adhesion of forestomach and liver and a foreign body granuloma in the adhesion area
2000mg/kg : female (1/5)

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral LD50 values were >2000 mg/kg for rat. The major toxicity was squamous hyperplasia of the forestomach.
Executive summary:

In this study, tetrahydromethylphthalic anhydride (MTHPA) was studied for oral toxicity in rats in a single dose toxicity test at doses of 0, 500, 1000 and 2000 mg/kg for both sexes. No deaths occurred of either males or females. Clinical signs of hypoactivity, bradypnea and prone position were observed in males and females of the 2000 mg/kg group on the day of administration. Decrease of body weights was observed in males of the 2000mg/kg group and suppression of body weight gain was observed in females of the 2000mg/kg group on the day of administration. At necropsy, thickening of the forestomach mucosa was observed in males and females of the 1000 and 2000 mg/kg groups most likely caused by the irritative properties of the test substance. Adhesion of forestomach and liver was noted in one female of the 2000 mg/kg group. Histopathologically, squamous hyperplasia and granulomatous inflammation in submucosa of the forestomach were observed in the 1000 and 2000 mg/kg groups. A foreign body granuloma in the adhesion area was also noted in the female of the 2000 mg/kg group. As the result, LD50 value was decided as >2000 mg/kg.