Registration Dossier

Administrative data

Description of key information

Acute oral: LD50 > 2000 mg/kg
Acute inhalation: LC50> 24.4 mg/L (air)
Acute dermal: LD50 > 2000 mg/kg bw

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:
1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study onducted under OECD guidelines
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Male and female rats were supplied by Charles River, Margate, Kent, UK.
At the start of the main study the males weighed 218- 229g and the females 206-238g and were 8-12 weeks of age.
After acclimatisation period of at least five days the animals were selected at random and given a number 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 a solid-floor polypropylene cages furnished with woodflakes.
Free access to drinking water and food (Rat and Mouse Expanded Diet No. 1, Special diets Services Limited, Witham, Essex UK), except for overnight fast immediately before dosing and for approx. 3-4 hr after dosing.
The animal room was maintained at a temperature of 20 to 21 °C and relative humidity of 46-55%. The rate of air exchange was approx. 15 changes per hr and the lighting was controlled by a time switch to give 12 hr continous light and 12 hr darkness.



Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
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 to its fasted bodyweight at the time of dosing.
Doses:
Range finding study: 2000 mg/kg (200 mg/ml; 10 ml/kg)
Main study: 2000 mg/kg (200 mg/ml; 10 ml/kg)
No. of animals per sex per dose:
Range finding: 1 male, 1 female
Main study: 5 males, 5 females
Control animals:
no
Details on study design:
Range finding: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hr after dosing and subsequently once daily for five years.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual tratment volumes. No necropsies were performed.

Main study: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hr after dosing and subsequently once daily for 14 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 thoractic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Preliminary study:
range finding study: there were no deaths or clinical signs of toxicity
Based on this info. a dose level of 2000 mg/kg bodyweight was selected for the main study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There where no deaths in males and females
Clinical signs:
No signs of systemic toxicity were noted during the study
Body weight:
All animals showed an expected gain in bodyweight during the study
Gross pathology:
No abnormalities were noted
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 in rats was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material in Sprague-DawleyCD strain rat. This study followed OECD guideline 401 (acute oral toxicity). Following a preliminary range-finding study, a group of 5 males and 5 females was given a single oral dose of test material as a suspension in arachis oil BP at a dose level of 2000 mg/kg bodyweight. The animals were observed for 14 days after the day of dosing and were killed and subjected to gross pathological examination.

There were no deaths, and no signs of systemic toxicity were noted during the study. All animals showed an expected gain in bodyweight during the study. No abnormalities were noted at necropsy. LD50 was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Klimisch 1

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in International Research and Development Corporation
Qualifier:
no guideline available
Principles of method if other than guideline:
Male and female rats were housed individually in a wire mesh cages and kept through out the experiment in controlled temperature and humidity.
Food and water was supplied ad libitum except when rats were in the control chamber.
During exposure rats were caged individually in a exposure cages, with a constant chamber airflow.
the dust athmosphere of the compound is generated by dispersing the powder at a calculated rate with a specially constructed dust generator.
Observations for pharmacotoxic signs and mortality are being conduced.
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Charles river CD
Sex:
male/female
Details on test animals and environmental conditions:
5 males and 5 females
Weight: 286-300 gr (males); 229-240 gr (females)
Rats were housed individually in wire-mesh cages and kept throughout the pre- and post- exposure periods in a temperature and humidity controlled room.
Purina laboratory Chow and water were supplied ad libitum except when rats where in the exposure chamber.
During exposure the rats were caged individualy in compartmented wire-mesh exposure cages.
The cages were placed in a 160 liter cubical stainless steel glass chamber. A constant chamber airflow was maintained by means of a rotary centrifugal air pump located at the exhaust side of the chamber. The chamber exhaust was filtered with an activated charcoal filter and a cambridge Absolute filter before being discharged outside of the laboratory.
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Dust Atmosphere: The dust atmosphere of the compound was generated by dispersing the powder at a calculated rate, with a specially constructed dust generator located near the chamber air inlet at the top of the exposure chamber. This dust generator consisted of a revolving plate with calibrated "cups" for transporting a known quantity of powder per unit time from a reservoir to a "blowhole". At the "blowhole" the powders in a "cup" were dispered into the chamber by a jet of air blowing at the rate of 10 L/min. The dusts emerging from the dust generator were diluted by the incoming chamber air at the rate of 5 L/min.
The actual quantity of powder disseminated (21.97 g/hr) was determined by weighing the quantity of powder in the reservoir before and after the experiment. The concentration of the dusts (24.4 mg/l) in the chamber atmosphere was calculated from the ration of the rates of powder dissimination (366.2 mg/min) to the total chamber airflow (15 L/min, the volume of air ejected from the dust generator plus the volume of make-up air).
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
1 h
Concentrations:
24.4 mg/l (nominal concentration)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
Observations for pharmacotoxic signs and mortality were made durnig and immediately following the 1 hr exposure period and daily thereafter for 14 days. Individual body weights were recorded prior to the 1 hr exposure and periodically thereafter in order to detect any transient effects following the exposure. All surviving rats were sacrificed and discarded at the end of the 14 day observation period.

Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 24.4 mg/L air (nominal)
Mortality:
None of the animals died during the experiment.
Clinical signs:
All rats appeared normal throughout the 14 day observation period.
Body weight:
Body weight gain of all rats appreared unaffected throughout the 14 days observation period.
Other findings:
increase inrespiratory rate during the exposure
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance was found to be non toxic by inhalation.
Executive summary:

Inhalation exposure of rats for 1 hr to a dust atmosphere of CH-100 -993, 975 -64 at a nominal concentration of 24.4 mg/l resulted in an increae in respiratory rate during the exposure. No other adverse effects were observed postexposure. No deaths occured during the experimental period and the body weight gain of all the rats appeared unaffected.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
24.4 mg/m³
Quality of whole database:
Klimisch 2

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:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted using OECD guidelines
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Five males and five females (Wistar; RccHan:WIST) supplied by Harlan laboratories UK.
On receipt the animals were randomly allocated to cages. Females were nulliparous and non-pregnant.
After acclimatisation of at least five days the animals were selected at random and given a number unique within a study by ink marking on the tail and a number written on a cage card. At the start of the studythe animals weighed at least 200g and were 8-12 weeks of age. The weight variation did not exceed ± 20% of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed ihdividually during the 24 hr exposure period and in groups of five by sex for the reminder of the study.
Free access to drinking water and food was allowed throughout the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. The rate of air exchange was at least 15 changes per hr and the lightning was controlled by a time switch to give 12 hr continous light and 12 hr darkness.



Type of coverage:
semiocclusive
Vehicle:
arachis oil
Remarks:
arachis oil BP
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair. The appropriate amount of test item was moisten with arachis oil BP and applied evenly as possible to an area of shorn skin. A piece of surgical gauze was placed over the the treatment area and semi-occluded with a piece of self adhesive bandage. Theanimals were caged individually for the 24 hr exposure period. Shortly after dosing the dressings were examined to ensure that they were securly in place.After the 24 hr contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with a suitable solvent to remove any residual test item. The animals were returned to group housing for the reminder of the study period.

Duration of exposure:
24 hr contact period
Doses:
2000mg/kg test substance
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not specified
Details on study design:
The animals were observed for deaths and signs of toxicity 0.5, 1, 2 and 4 hr after dosing and subsequently once daily for 14 days.
After removal of the dressings and subsequently once daily for 14 days, the test sites were examimed for the evidence of primary irritation and scored according to draize JH (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.
Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoractic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
no sign of systemic toxicity
Body weight:
All animals showed expected gains in bodyweight over the study period
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
Dermal reactions: Very slight erythema was noted at the test site of all males and three females. Small superficial scattered scabs were also noted at the test site of one female. There were no signs of dermal irritation noted at the test sites of two females.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

Acute dermal toxicity was conducted in Wistar rats using the following guidelines, OECD 402; Method B3 Acute Toxicity; OPPTS 870.1200.

A group of five males and five females was given a single 24 hr semi-occluded dermal application at a dose of 2000 mg/kg bodyweight. clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

No deaths, no signs of systemic toxicity and no abnormalities were evident at the end of the experiment.

All animals showed expected gaind in bodyweight and very slight erythema was noted at the test sites of eight animals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Klimisch 1

Additional information

The test substance was found to be non toxic to rats following the three acute tests; oral, inhalation and dermal toxicity.


Justification for selection of acute toxicity – oral endpoint
Experimental data available

Justification for selection of acute toxicity – inhalation endpoint
Data available

Justification for selection of acute toxicity – dermal endpoint
Experimental data available

Justification for classification or non-classification

The above results triggered no classification under the EEC criteria for classification and labelling requirements for Dangerous Substances and Preparations (67/548/EEC) and the CLP Regulation (EC No 1272/2008). Therefore, the substance is not classified for acute toxicity.