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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:
16 February 1989 - 8 March 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across to similar substance. Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Justification for type of information:
See read-across justification in Section 13.
Cross-reference
Reason / purpose:
other: Target substance
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read across material
Justification for type of information:
See read-across justification in Section 13.
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.

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:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Description: White powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bantin & Kingman Ltd., Grimston, Aldborough, Hull, U.K
- Age at study initiation: 5 – 8 weeks
- Weight at study initiation: Males 121 – 131g; Females 120 – 145 g
- Fasting period before study: Overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: The animals were housed in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet (e.g. ad libitum): ad libitum with the exception of fasting period. Free access to food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.)
- Water (e.g. ad libitum): ad libitum with the exception of fasting period. Free access to mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23°C
- Humidity (%):50 - 58%. relative
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

IN-LIFE DATES: From: To: 22 February 1989 - 8 March 1989

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material preparation at a dose level of 5000 mg/kg bodyweight.
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
Procedure
a) Range-finding Study
In order to establish a suitable dose level for the main study groups of two rats (one male and one female) were treated once only as follows:

Dose Level (mg/kg) Concentration (mg/mL) Dose Volume (mL/kg) Number of Rats
Male Female
5000 500 10 1 1
3000 300 10 1 1
1000 100 10 1 1
250 25 10 1 1

Animals were observed 1 and 4 hours after dosing and then daily for five days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.


b) Main Study
A group of ten rats (five males and five females) was dosed as follows in order to confirm the findings of the range-finding study:


Dose Level (mg/kg) Concentration (mg/mL) Dose Volume (mL/kg) Number of Rats
Male Female
5000 500 10 5 5

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Deaths and evidence of overt toxicity were recorded at each observation.
Individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14.
All animals were subjected to gross necropsy examination for any macroscopic abnormalities. No tissues were retained.
Statistics:
Evaluation of Data
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made. Clinical observations, bodyweight and necropsy records were examined for any adverse but nonlethal effects resulting from treatment.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Mortality Data

Range-finding Study:
No deaths (0/2)

Main Study
No Deaths (0/10)
Body weight:
All animals showed expected gain in bodyweight over the study period
Gross pathology:
No abnormalities were noted at necropsy of animals killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material, SUBSTANCE 1658/5, in the Sprague-Dawley CFY strain rat was found to be greater than 5000 mg/kg bodyweight.
Executive summary:

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CFY strain rat was found to be greater than 5000 mg/kg bodyweight.

The study was designed to comply with the recommendations of the OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity" referenced as method B1 in Annex V of EEC Commission Directive 84/449/EEC.