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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:
From February 18 to February 28, 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Necropsy of animals was not conducted. However, this deviation was not considered to have affected the scientific validity and interpretation of the results. No GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(Necropsy of animals was not conducted. However, this deviation was not considered to have affected the scientific validity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Clear pale yellow liquid on receipt, but solidified on storage at 0-5 ºC.
- Storage condition of test material: On its arrival the test substance was stored in the dark at ambient temperature. Following receipt of further information, the storage conditions were changed on 13th September 1990 to in the dark at between 0-5 ºC.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K. Ltd.
- Age at study initiation: 9-11 weeks
- Weight at study initiation: males: 190-269 g; females: 128-161 g
- Fasting period before study: fasted overnight
- Housing: Single sex groups of up to three rats in cages with stainless steel wire-mesh walls, floors and tops (33 cm x 22 cm x 16 cm). Paper-lined trays for excreta were placed beneath each cage and changes three times weekly.
- Diet (e.g. ad libitum): Pelleted diet (LAD1, Special Diet Services Ltd.), ad libitum.
- Water (e.g. ad libitum): from the public supply, ad libitum.
- Acclimation period: The animals were quarantined for a minimum of four days in a non-barrier animal room with access restricted to essential personnel. At least five days before dosing the animals were rehoused.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 ºC
- Humidity (%): 30-70%
- Air changes (per hr): not documented.
- Photoperiod (hrs dark / hrs light): 12 hour day and 12 hour night


IN-LIFE DATES: From February 18 to February 28, 1991

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Animals were fasted overnight, weighed and given a single dose of the undiluted test material by gavage, using a ball pointed cannula and syringe.
Doses:
Animals were dosed at 1000, 1710, 2924 and 5000 mg/kg. The undiluted test material was administered at dose volumes of 1.06, 1.82, 3.11 and 5.32 ml/kg.
No. of animals per sex per dose:
Five animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A detailed clinical examination was made six times on the day of dosing and twice daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 8 and Day 15 bodyweights were recorded and changes in bodyweight calculated.
- Necropsy performed: no
Statistics:
The 14 day LD50, 95% confidence interval and the dose-mortality slope were calculated using a method based on probit analysis (Finney, 1977).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 976 mg/kg bw
Based on:
test mat.
95% CL:
2 667 - 3 551
Mortality:
Mortalities occurred on Days 2, 3 and 4 among rats dosed at 2924 and 5000 mg/kg. No rat survived treatment at the highest of these dose-levels.
Clinical signs:
The principal clinical signs observed among rats dosed with the test substance were piloerection, lachrymation, hunched posture, abasia/ataxia and/or prostration, diarrhoea, yellow staining of the anogenital fur and an unkempt appearance. There were additional cases of tachypnoea or bradypnoea, twitching and coma preceding death among those treated at the high dose-level. Other isolated clinical signs included salivation, periorbital encrustation and eye closure.
Onset of hunched posture, abasia and diarrhoea among rats treated at the intermediate or high dose levels was common within one-half hour of dosing and at the low dose level occurred within 3 hours of dosing. Other principal signs of reaction were established by Day 2. Recovery, as judged by external appearance and behaviour, was advanced by Day 3 but incomplete until Day 4 (1000 mg/kg) or Day 11 (1710 and 2924 mg/kg).
Body weight:
Low bodyweight gains or losses of bodyweight during the first week of the study were apparent among rats treated at 1710 or 2924 mg/kg. Despite this, all surviving rats had gained weight relative to their Day 1 bodyweights by the end of the 14 day observation period.

Any other information on results incl. tables

Table 7.2.1:      Summary of Acute Oral Toxicity

Males

Females

Dose

Mortality

Time of death

Dose

Mortality

Time of death

1000 mg/kg

0/5

--

1000 mg/kg

0/5

--

1710 mg/kg

0/5

--

1710 mg/kg

0/5

--

2924 mg/kg

1/5

Day 4

2924 mg/kg

3/5

Day 2

5000 mg/kg

5/5

Days 2-3

5000 mg/kg

5/5

Days 2 -3

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 for the test substance is 2976 mg/kg.
Executive summary:

Groups of five rats per sex were dosed at 1000, 1710, 2924 and 5000 mg/kg. A detailed clinical examination was made six times on the day of dosing and twice daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 8 and Day 15 bodyweights were recorded and changes in bodyweight calculated. Animals surviving to the end of the study were killed by carbon dioxide asphyxiation. Mortalities occurred on Days 2, 3 and 4 among rats dosed at 2924 and 5000 mg/kg. No rat survived treatment at the highest of these dose-levels. The acute oral LD50 for the test substance is 2976 mg/kg.