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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July - September 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well conducted study in accordance with methods regarded as similar/equivalent to current OECD guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Study pre-dates introduction of OECD test methods. Study design similar/equivalent to OECD test methods
GLP compliance:
yes
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): Methyl endo-methylene tetrahydro phthalaic anhydride (MHAC-P)
- Physical state: Liquid
- Lot/batch No.: 6953

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 99 - 133 g
- Fasting period before study: Overnight
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: July 1980 To: September 1980

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 4.0mL/kg body weight
Doses:
0.0, 0.5, 1.0, 1.6, 2.5, 5.0 g/kg body weight
No. of animals per sex per dose:
5 male / 5 female
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed daily, weighed weekly
- Necropsy of survivors performed: yes
Statistics:
Probit analysis by method of Finney

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
Based on:
test mat.
95% CL:
1 100 - 1 600
Mortality:
0.0 g/kg - 0/5 males: 0/5 females
0.5 g/kg - 0/5 males: 0/5 females
1.0 g/kg - 1/5 males: 0/5 females
1.6 g/kg - 3/5 males: 5/5 females
2.5 g/kg - 5/5 males: 5/5 females
5.0 g/kg - 5/5 males: 5/5 females
Clinical signs:
Signs of reaction to treatment, observed shortly after dosing in all treated animals included piloerection, abnormal body carriage (hunched posture) and abnormal gait (waddling). These were accompanied by: lethargy, a decreased respiratory rate, pallor of the extremities, increased lachrymation, ptosis, diarrhoea and diuresis amongst rats treated at 1.0 g/kg and above; rales in one female dosed at 1.0 g/kg and one male and two females dosed at 1.6 g/kg; loss of the righting reflex and ataxia in one female dosed at 2.5 g/kg; gasping in one female dosed at 2.5 g/kg; a comatose-like condition prior to death in one female dosed at 2.5 g/kg and two females dosed at 5.0 g/kg; increased salivation amongst all treated rots in the first two hours of observation only; Piloerection only was seen in the controls.
Death occurred amongst rats treated at 1.0 g/kg and above from within one hour to two days of dosing.
Recovery of the survivors, as judged by external appearance and behaviour, was apparently complete within ten days of dosing.
Body weight:
Reduced bodyweight gains were observed in male rats at treated at.0 and 1.6 g/kg during the first week of observation only. Normal bodyweight gains were observed in male and female rats treated at 0.5 g/kg and female rats treated at 1.0 g/kg, when compared with the controls, throughout the two week observation period.
Gross pathology:
Autopsy revealed congestion and haemorrhages in the lungs and pallor of the liver, spleen and kidneys. These findings were accompanied by: congestion of the intestinal blood vessels amongst rats treated at 1.6 g/kg and above; a creamy-coloured film on the liver in one male and female treated at 2.5 g/kg and three males and females at 5.0 g/kg; haemorrhage of the large intestine and discolouration of its contents in one male treated at 5.0 g/kg; discolouration of the large intestinal contents in one female treated at 5.0 g/kg. Terminal autopsy findings (those animals surviving treatment) were within normal limits.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute toxicity has been determined in the rat following administration of a single oral dose. The median lethal dose (LD50) was determined to be 1300 mg/kg body weight.
Executive summary:

Acute toxicity has been determined in the rat following administration of a single oral dose using method regarded a similar or equivalent to OECD test methods. The median lethal dose (LD50) was determined to be 1300 mg/kg body weight.