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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:
1988-11-11 to 1989-01-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Annex V of the EEC Directive 79/831/EEc, Part B Methods for determination of toxicity. Method B1 Acute Oral Toxicity
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Solfit
- Physical state: Clear colourless liquid
- Analytical purity: 99.9% u.p.
- Lot/batch No.: L-754148
- Storage condition of test material: Solfit was received on 7 November 1988 and stored in the original container at 4°C
- Other: Solfit was administered, as supplied by the Sponsor, at a volume not exceeding 5.39 ml/kg (specific gravity 0.927) in the main study. The absorption of the test substance was not determined. The homogenity, stability and purity of the test substance were the responibility of the Sponsor.

Test animals

Species:
rat
Strain:
other: Crl:CD®(SD) BR VAF plus
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Portage, Michigan, USA
- Age at study initiation: Approximately four to six weeks of age
- Weight at study initiation: Weight range of 132 to 158 g prior to dosing (Day 1)
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing
- Housing: They were housed in groups of up to five rats the same sex in metal cages with wire mesh floors
- Diet (e.g. ad libitum): A standard laboratory rodent diet (Labsure LAD 1) were provided ad libitum
- Water (e.g. ad libitum): Domestic quality potable water were provided ad libitum
- Acclimation period: A minimum period of 14 days prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean daily minimum and maximum temperatures of the animal room were 21°C and 22°C respectively
- Humidity (%): Mean daily relative humidity value was 53% R.H.
- Air changes (per hr): The rate of air exchange was maintained at approximately 15 air changes/hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to provide 12 hours artificial light in each 24-hour period

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Treatment procedure: The appropriate dose volume (volume not exceeding 5.39 ml/kg (specific gravity 0.927) in the main study) of the test substance was administered to each rat using a syringe and plastic catheter (8 choke)

Doses:
2.0, 3.2, 4.0, 5.0 g/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (day of dosing) (a period of six hours). On subsequent days the animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on week days or 11.30 hours on public holidays, including Saturday and Sunday. Clinical signs were recorded at each observation. The following were recorded: Approximate time of death of individual rats; The nature, severity, approximate time of onset and duration of each toxic sign; Individual bodyweights of rats on Day 1 (day of dosing), 8 and 15 and at death.
- Necropsy of survivors performed: yes
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of: Finney (1971) Probit Analysis (3rd Editon) Cambridge University Press.
Seperate LD50 values for male and females were estimated by undertaking probit analysis on the mortality data by fitting two parallel lines on the data (males only and females only) unsing the techique described by Finney (1978, Statistically Method in Biological Assay, 3rd Edition, Charles Griffin, London).
A chi-squared test was carried out to check that the data did not certain any evidince for non-parallelism.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4.4 other: g/kg bw
95% CL:
>= 3.9 - <= 5.2
Sex:
male
Dose descriptor:
LD50
Effect level:
4.5 other: g/kg bw
95% CL:
>= 3.9 - <= 5.6
Sex:
female
Dose descriptor:
LD50
Effect level:
4.3 other: g/kg bw
95% CL:
>= 3.6 - <= 5.3
Mortality:
Deaths occurred amongst male and female rats dosed at 4.0 g/kg and above. Deaths occurred from within two hours of dosing until Day 3.
Clinical signs:
Pilo-erection was observed in all rats within 5 minutes of dosing and throughout the reminder of Day 1. This was accompanied by:
-Pilo-errection, lethargy and pallor of the extremities within 5 minutes of dosing in all rats,
-abnormal body carriage (hunched posture) and abnormal gait (waddling) within 5 minutes of dosing in all rats dosed at 2.0, 4.0 and 5.0 g/kg and females dosed at 3.2 g/kg, and at later intervals on Day 1 in male rats dosed at 3.2 g/kg,
-ataxia within 5 minutes of dosing in males dosed at 3.2 g/kg,
-decreased respiratory rate and ptosis within five minutes of dosing in rats dosed at 3.2 g/kg, and at later intervals on Day 1 in rats dosed at 4.0 and 5.0 g/kg.
-prostration in two males and two females dosed at 4.0 g/kg and in three males and one female dosed at 5.0 g/kg,
-pink extremities in three males and one female dosed at 5.0 g/kg.
Recovery, as judged by external appearance and behaviour, was completed by Day 2,3 or 4.
Body weight:
Slightly low bodyweight gains were recorded for one female dosed at 2.0 g/kg, one female dosed at 3.2 g/kg and one male and three females dosed at 4.0 g/kg on Day 8 of the study.
The majority of rats achieved anticipated bodyweight gains during the second week of the study

No change in bodyweight or bodyweight losses were recorded for rats that died.
Gross pathology:
Terminal autopsy findings were normal.
Slightly pale cortex (kidney) was observed post-mortem in three males and three females (5.0 g/kg) and one female (4.0 g/kg) that died. Autopsy of rats that died revealed no other macroscopic abnormalities.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute LD50 of the substance determined in this study is 4.4 g/kg bw for males and females combined
Executive summary:

The acute oral toxicity of Solfit was evaluated in this single-dose study in rats. The appropriate dose volume of the test substance was administered to each rat by oral gavage. The study was conducted according to an appropriate national standard method and in compliance with GLP. Mortality, clinical observations, body weight and necropsy findings were evaluated. Deaths occurred amongst male and female rats dosed at 4.0 g/kg and above. Deaths occurred from within two hours of dosing until Day 3. No change in bodyweight or bodyweight losses were recorded for rats that died. Slightly pale cortex (kidney) was observed post-mortem in three males and three females (5.0 g/kg) and one female (4.0 g/kg) that died. Autopsy of rats that died revealed no other macroscopic abnormalities. The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of Solfit were estimated to be:

Males and females combined: 4.4 (3.9 to 5.2) g/kg bw

Males only:                              4.5 (3.9 to 5.6) g/kg bw

Females only:                           4.3 (3.6 to 5.3) g/kg bw