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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:
21 March 1990 - 20 April 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study protocol was not in accordance with modern guidelines, which for example would have required fewer animals, but the scientific basis of the method followed is nevertheless robust

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(animals were not observed 30 minutes after dosing)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):
- Substance type: Complex reaction product
- Physical state: Liquid
- Analytical purity: Assumed to be 100% pure for the purposes of dosing
- Impurities (identity and concentrations): NA
- Composition of test material, percentage of components: The study report does not contain information on test material characterisation or analysis; it confirms this information is held by the study sponsor Paramins Technology (now Infineum)
- Isomers composition: NA
- Purity test date: NDA.
- Lot/batch No.: I.
- Expiration date of the lot/batch: NDA.
- Stability under test conditions: NDA.
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
other: Crl:CDBr (Sprague-Dawley)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Kingston Facility, Stone Ridge, New York.
- Age at study initiation: Males, approximately 8 weeks old; females, approximately 11 weeks old.
- Weight at study initiation: Males 230–243 g; females 203–211 g.
- Fasting period before study: Food witheld overnight prior to dosing.
- Housing: Individual, except during the first week of acclimation. Suspended stainless steel cages.
- Diet (e.g. ad libitum): Ad libitum.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: 7 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-76 ºF (20-24.4ºC).
- Humidity (%): 30-70%.
- Air changes (per hr): Not stated.
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark.


IN-LIFE DATES: From: 22 March 1990 To: 05 April 1990.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.96 mL/kg.
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations : Animals were observed for viability and signs of toxicity at 1, 2, 4 and 6 hours after dosing and at least daily thereafter.
- Frequency of weighing: Individual bodyweights were recorded prior to dosing, at initiation of dosing (Day 0), and at Day 7 and Day 14 (or at death for animals dying during the study).
- Necropsy of survivors performed: Yes.
Statistics:
The mean and standard deviations of the body weights and body weight changes were calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
2 000 mg/kg bw
Remarks on result:
other: Estimated LD50
Mortality:
Five (2 male and 3 female) animals died on the day of dosing (Day 0). The remaining five animals survived to termination.
Clinical signs:
In-life signs of toxicity most frequently observed included: tremors; oral, nasal and ocular discharge; staining of the anogenital and abdominal areas. Other signs included hypoactivity, hypothermia, abnormal stool production, hyperactivity, convulsions and rales. Surviving animals showed no signs of toxicity from Day 7 onwards.
Body weight:
The five animals that survived until study termination showed an increase in body weight over the initial values.
Gross pathology:
Gross pathology of animals that died during the study included abnormalities of the gastrointestinal tract, liver and lungs. Single incidences of undescended testes and an abnormal white mass within the urinary bladder were also noted. No gross pathology was found in surviving animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Five of the ten animals died on the day of dosing. Necropsy of these animals revealed abnormalities of the gastrointestinal tract, liver and lungs. Single incidences of undescended testes and an abnormal white mass within the urinary bladder were also noted. The five remaining animals survived until study termination and displayed no gross pathology at necropsy. Based on the five deaths, an approximate LD50 of 2,000 mg/kg may be estimated.
Executive summary:

The test material was assessed for acute oral toxicity potential in a GLP study (limit test) in Sprague-Dawley rats. Five males and five females were administered the neat test material by gavage at a dose of 2,000 mg/kg bodyweight and observed for 14 days. Body weights were measured prior to dosing, one week after dosing, and prior to termination. Two males and three females died on the day of dosing. Gross necropsy of these animals revealed abnormalities of the gastrointestinal tract, liver and lungs. Single incidences of undescended testes and an abnormal white mass within the urinary bladder were also noted. The five remaining animals survived until study termination and displayed no gross pathology at necropsy. Based on the five deaths, an approximate LD50 of 2,000 mg/kg may be estimated.