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Administrative data

Description of key information

Two acute oral toxicity studies were available.  The LD50 in both studies exceeds 2000 mg/kg. 
One acute dermal toxicity study was available. The LD50 exceeds 2000 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - May 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to GLP
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals and Animal Husbandry
Male and female Sprague-Dawley CD (Cri : CD ® BR) strain rats supplied by
Charles River (UK) Ltd., Margate, Kent, UK. were used. At the start of the main
study the males weighed 204 to 219g, and the females 204 to 228g, and were
eight to twelve weeks of age. After an acclimatisation period of at least five
days the animals were selected at random and given a number unique within
the study by indelible ink-marking on the tail and a number written on a cage
card.

The animals were housed in groups of up to five by sex in solid-floor
polypropylene cages furnished with woodflakes. With the exception of an
overnight fast immediately before dosing and for approximately three to four
hours after dosing, free access to mains drinking water and food (Rat and
Mouse Expanded Diet No.1, Special Diets Services limited, Witham, Essex,
UK) was allowed throughout the study.

The animal room was maintained at a temperature of 19 to 24· C and relative
humidity of 47 to 54%. The rate of air exchange was approximately fifteen
changes per hour and the lighting was controlled by a time switch to give
twelve hours continuous light and twelve hours darkness.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
2.27 ml/kg bw was given; with a density of 0.882, this resulted in 2000 mg/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other:
Details on study design:
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.

The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and
4 hours after dosing and subsequently once daily for fourteen days.
Individual bodyweights were recorded prior to dosing on Day 0 and on
Days 7 and 14.

At the end of the study the animals were killed by cervical dislocation and
subjected to gross pathological examination. This consisted of an external
examination and opening of the abdominal and thoracic cavities for
examination of major organs. The appearance of any macroscopic

Evaluation of Data

Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.

Using the mortality data obtained, an estimate of the acute oral median lethal
dose (LD50) of the test material was made .
abnormalities was recorded. No tissues were retained.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: In two females hunched posture and lethargy was observed two hours to one day after dosing. All animals were normal on day 2.
Gross pathology:
Effects on organs: No abnormalities.
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LD50 in rats is greater than 2000 mg/kg.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method 81 of Commission Directive 92169/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of undiluted test material, at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Reliable without restrictions.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - May 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to GLP
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals and Animal Husbandry
Five male and five female Sprague-Dawley CD (Crl : CD ® BR) strain rats
supplied by Charles River (UK) Ltd, Margate, Kent were used. At the start of
the study the males weighed 206 to 228g, and the females 209 to 233g, and
were approximately eight to twelve weeks old. After a minimum
acclimatisation period of five days the animals were selected at random and
given a number unique within the study by indelible ink-marking on the tail
and a number written on a cage card.

The animals were housed in suspended polypropylene cages furnished with
woodflakes. The animals were housed individually during the 24-hour
exposure period and in groups of five, by sex, for the remainder of the study.
Free access to mains drinking water and food (Rat and Mouse Expanded Diet
No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed
throughout the study.

The animal room was maintained at a temperature of 19 to 24 degrees C and relative
humidity of 47 to 54%. The rate of air exchange was approximately fifteen
changes per hour and the lighting was controlled by a time switch to give
twelve hours continuous light and twelve hours darkness.
Type of coverage:
semiocclusive
Vehicle:
other: None, test material was administered as supplied
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
For the purpose of the study the test material was used as supplied. The
specific gravity was determined and used to calculate the appropriate dose
volume for the required dose level.

On the day before treatment the back and flanks of each animal were clipped
free of hair using veterinary clippers.

DOSE LEVEL(mg/kg): 2000
SPECIFIC GRAVITY: 0.882
DOSE VOLUME (ml/kg): 2.27

The calculated volume of the test material, as received, was applied uniformly
to an area of shom skin (approximating to 10% of the total body surface area)
using a graduated syringe. A piece of surgical gauze was placed over the
treatment area and semi-occluded with a piece of self-adhesive bandage. The
bandage was further secured with a piece of BlENDERM wrapped around each
end. The animals were caged individually for the 24-hour exposure period.
Shortly after dosing the dressings were examined to ensure that they were
securely in place.
The animals were observed for deaths or overt signs of toxicity l/2, 1,2 and
4 hours after dosing and subsequently once daily for fourteen days.
After the 24-hour contact period the bandage was carefully removed and the
treated skin and surrounding hair wiped with cotton wool moistened with
distilled water to remove any residual test material. The animals were returned
to group housing for the remainder of the study period.
After removal of the dressings and subsequently once daily for fourteen days,
the test sites were examined for evidence of primary irritation and scored
according to the following scale from Draize J H (1977) "Dermal and Eye
Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of
Household Substances, National Academy of Sciences, Washington DC p.31:
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: no signs of systemic toxicity were noted during the study.
Gross pathology:
Effects on organs: no abnormalities noted at necropsy.
Other findings:
Signs of toxicity (local): no effects of skin irritation or any other local effects were noted during the study.
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50 of the test material, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg
bodyweight.
Executive summary:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

A group of ten animals (five males and five females) was given a single 24-hour, semioccluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination. There were no deaths. No signs of systemic toxicity or skin irritation were noted during the study. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LDso) of the test material in the SpragueDawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Reliable without restrictions.

Additional information

Both the oral and dermal LD50 value were in excess of 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Apparently well conducted GLP study.

Justification for classification or non-classification

Based on the outcome of the acute toxicity tests, no classification is needed for acute toxicity.