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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:
27 October 1889 - 1 December 1989
Reliability:
1 (reliable without restriction)

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)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material: ESD0021175
- Expiration date of the lot/batch: 2017-11-27
- Apperance: colourless waxy solid
- Storage condition of test material: Refrigerator (2 to 8 °C)

- Purity: 35% (w/v) solution in water
- Date of arrival: 14 September 1989
- Storage conditions: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
1. Animals and Animal Husbandry
Ten male and ten female Sprague-Dawley strain rats were supplied by Bantin & Kingman Ltd., Aldborough, Hull, U.K.
At the start of the study the males weighed 120 - 155g, and the females 122 - 144g, and were approx imately five to eight weeks old. After a
minimum acclimatisation period of five days the animals were selected at random and given a unique number within the study by ear punching
and a number written on a cage card.
The animals were housed in groups of up to five by sex in solid-floor poly propylene cages with sawdust bedding. With the exception of an
overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and
Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.
The animal room was maintained at a temperature of 20 - 23°C and relative humidity of 50 - 68%. The rate of air exchange was approximately
15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
A group of ten rats (five males and five females) was dosed as follows:
DOSE LEVEL [mg/kg]: 2000
SPECIFIC GRAVITY: 0.974
DOSE VOLUME [ml/kg] 2.06
NUMBER OF RATS:
MALE 5 FEMALE 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 orn days 7 and 14 or at death.
All animals were subjected to gross necropsy examination for any macroscopic abnormalities. No tissues were retained.
Deaths occurred and an additional group of ten rats (five males and five females) was treated as follows:

DOSE LEVEL [mg/kg]: 200
CONCENTRATION [mg/ml]: 20
DOSE VOLUME [ml/kg]: 10
NUMBER OF RATS:
MALE 5 FEMALE 5

Doses:
2000 mg/kg bodyweight
and 200 mg/kg bodyweight
No. of animals per sex per dose:
5 male and 5 female rats
Control animals:
no
Details on study design:
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 orn days 7 and 14 or at death.
All animals were subjected to gross necropsy examination for any macroscopic abnormalities. No tissues were retained.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Mortality:
Mortality at dose level 2000 mg/kg bw: 8/10 (4 males and 4 females).
Deaths occurred in males on day 1, 2, 5 and 6 after dosing. In females deaths occured one hour after dosing, on day 3 (one female) and on day 4 (two females).
Mortality at dose level 200 mg/kg bw: 0/10 .
No animal of the 200 mg/kg bw dose group died.
Clinical signs:
Major signs of toxicity noted in animals treated with 2000 mg/kg were hunched posture, pilo-erection and lethargy.
Occasional or isolated signs of decreased respiratory rate, increased salivation, pallor of the extrem ities, ataxia and red/brown staining around
the snout were also noted.
The surviving male appeared normal five days after treatment and the surviving female appeared normal one day after treatment.
Body weight:
The surviving male treated with 2000 mg/kg bodyweight showed reduced body weight gain over the first week.
All other animals showed expected gain in bodyweight over the study period.
Gross pathology:
Common abnormalities noted at necropsy of animals that died during the study were abnormally red lungs, dark liver and kidneys and
haemorrhage of the glandular and non-glandular gastric epithelia and small and large intestines.
No abnormalities were noted at necropsy of surviving animals killed at the end of the study.

Any other information on results incl. tables

A group of ten fasted animals (five males and five females) was given a single oral dose of test material at a dose level of 2000 mg/kg bodyweight. Eight animals(four males and four females) died and a further group of ten animals was treated at a dose level of 200 mg/kg bodyweight.

Deaths in the 2000 mg/kg dose group were noted one hour after dosing and one to six days after treatment.Signs of toxicity noted in this group were hunchedposture, pilo-erection, lethargy with incidents of decreased respiratory rate, increased salivation, pallor of the extremities, ataxia and red/brown stainingaround the snout. No signs of systemic toxicity were notedin animals treated with 200 mg/kg bodyweight.

The surviving male treated with 2000 mg/kg bodyweight showed reduced bodyweight gain at the end of the first week. All other animals showed expected gain in bodyweight over the study period.

Common abnormalities noted at necropsy of animals that died during the study were abnormally red lungs, dark liver and kidneys and haemorrhage of theglandular and non-glandular gastric epithelia and small and large intestines.No abnormalities were noted at necropsy of surviving animals killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material to the Sprague-Dawley strain rat was found to be
greater than 200 mg/kg bodyweight but less than 2000 mg/kg bodyweight.
According to the Dangerous Substance Directive the symbol "Xn" and risk phrase R 22 “HARMFUL IF SWALLOWED” are required.
Executive summary:

A group of ten fasted animals (five males and five females) was given a single oral dose of test material at a dose level of 2000 mg/kg bodyweight. Eight animals(four males and four females) died and a further group of ten animals was treated at a dose level of 200 mg/kg bodyweight. The acute oral median lethal dose (LD50) of the test material to the Sprague-Dawley strain rat was found to be

greater than 200 mg/kg bodyweight but less than 2000 mg/kg bodyweight.

Common abnormalities noted at necropsy of animals that died during the study were abnormally red lungs, dark liver and kidneys and haemorrhage of theglandular and non-glandular gastric epithelia and small and large intestines.No abnormalities were noted at necropsy of surviving animals killed at the end of the study.