Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: EU Method B.1, GLP. Adverse effect was observed. Therefore, the acute oral toxicity of Ethyl centralite is moderate.
Acute dermal toxicity: EU Method B.3, GLP. No adverse effect was observed. Therefore, the acute dermal toxicity of Ethyl centralite is low.
Acute inhalation toxicity: Toxicology Division Procedural Guide USAEHA. No adverse effect was observed. Therefore, the acute inhalation toxicity of Ethyl centralite is low.

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:
18.4. - 25.4.2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was carried out in accordance with internationally valid GLP principles.
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: TOP VELAZ s.r.o., Praha, Czech Republic- Weight at study initiation: 158-183 g- Fasting period before study: 20 h- Housing: 5 animals in one plastic breeding cage VELAZ T4- Diet (e.g. ad libitum): standard feeding mixture ST-1 ad libitum- Water (e.g. ad libitum): drinking tap water ad libitumENVIRONMENTAL CONDITIONS- Temperature (°C): 20-24°C- Humidity relative (%): 30-70%- Photoperiod (hrs dark / hrs light): 12-hour light/12 hour darkSTUDY TIME SCHEDULEExperimental part of study: 18.4.-25.4. 2001
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
PREPARATION OF APPLICATION FORMThe single volume of administered suspension was 1mL/100 g of animal body weight.VEHICLE- Concentration in vehicle:- Amount of vehicle (if gavage):- Justification for choice of vehicle:- Lot/batch no. (if required):- Purity:MAXIMUM DOSE VOLUME APPLIED:DOSAGE PREPARATION (if unusual):CLASS METHOD (if applicable)- Rationale for the selection of the starting dose:
Doses:
500, 700, 1000, 1500 mg/kg bw
No. of animals per sex per dose:
5 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Mortality: daily- Body weight recording: before application, on the 8th day of the study and at the end of the study- Clinical examination: the first day: twice (30 minutes and 3 hours after application), the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days- Necropsy of survivors performed: yes
Statistics:
Numeric value of toxicity was defined by Bliss method, using computer program PROBIT (VUOS 1991).
Sex:
female
Dose descriptor:
LD50
Effect level:
780.9 mg/kg bw
Based on:
test mat.
95% CL:
685.5 - 889.6
Mortality:
Dose 700 mg/kg2 animals after 2.15 and 5.5 hrs after applicationDose 1000 mg/kg4 animals 0.45 hrs after applicationDose 1500 mg/kgall animals died 0.15 - 04 hrs after application
Clinical signs:
Dose 500 mg/kg30 minutes after application: Piloerection, skin anaemia, discomfort, excitation, tremor, increased reactivity2nd day: no clinical changesDose 700 mg/kg30 minutes after application: Skin anaemia, discomfort, clonus, torpor, increased reactivity2nd day: no clinical changesDose 1000 mg/kgDiscomfort, clonospasm, increased reactivityDose 1500 mg/kgTremor, spasm, vocalization, dyspnoe, vocalization
Gross pathology:
Dose 500 mg/kgWithout pathological changesDose 700 mg/kg3 survivors - without pathological changes2 died animal - skin anaemia, mild lung congestion, intestine anaemia, mild liver, congestion, heart-block in systole (probably consequence of abdominal muscules contraction)Dose 1000 mg/kgMild lung congestion, stomach anaemia, flatulence, intestine anaemia, liver congestionDose 1500 mg/kgMild lung congestion, mild intestine anaemia, liver congestion

-

Interpretation of results:
harmful
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The test substance CENTRALIT is according to results of acute oral toxicity classified as harmful. The test substance caused clinical signs of intoxication – increase neuro-muscles irritability resulted in spasm. Pathological findings were insignificant.
Executive summary:

The aim of the study was to investigate acute toxic effects of the test substance Centralit, after a single oral administration to Wistar rats (females only). Result follows in test protocol No. 0127 (March, the 3rd, 2001), when after performing of limit test, higher sensitivity for females was found out.

The testing was performed according to Regulation of Ministry of health of the Czech Republic No. 251/1998 Sb., the Method B.1: Acute Oral Toxicity (per os). This method corresponds with the guideline OECD No. 401 (1987).

According to the study results, the value of LD50 (oral) for female rats is 780.9 mg/kg of body weight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
780.9 mg/kg bw
Quality of whole database:
The study is a GLP compliant and has Klimish score 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:
april 1976-april 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline study with acceptable restrictions.
Qualifier:
no guideline available
Principles of method if other than guideline:
Toxicology Division Procedural Guide, US Army Environmental Hygiene Agency (USAEHA), 1972
GLP compliance:
not specified
Species:
rat
Sex:
male
Route of administration:
inhalation
Duration of exposure:
8 h
Remarks on duration:
single exposure
Concentrations:
nominal concentration - 0.4, 198 mg/L
No. of animals per sex per dose:
6 males
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days- Body weight: pre-exposure day, post-exposure day 1, 3 ,7, 11- Necropsy of survivors performed: yes- Other examinations performed: body weight,organ-to-body weight ratios weights, histopathology
Sex:
male
Dose descriptor:
LC50
Effect level:
> 198 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
8 h

TEMPERATURE 23°C

Results: Rats exposed to a nominal concentration of 0.4 mg/L for 8 hours showed no toxic signs during exposures and for 14 days thereafter. Body weight gain and organ-to-body weight ratios of the exposed rats compared to the control rats were not significantly different. No exposure related histopathologic changes were noted in tissues and organs.

Interpretation: Compound has a low volatility and should present no acute inhalation hazard from single short term exposure.

TEMPERATURE 50°C

Results: No discernible loss of test material from dispersion tube was found. Rate showed no toxic signs during exposure and 14 days thereafter. Body weight gain and the organ-to-body weight ratios of liver, kidney, lung, spleen and testes from exposed rats compared to the control rats were not significantly different. No exposure related histopathological changes were noted in tissues and organs.

Interpretation: Compound has a low volatility and should present no hazard at room temperature due to the inhalation of ethyl centralite vapors.

TEMPERATURE 100°C

Results: Compound melted and vaporized from dispersion tube into exposure chamber, all compound had been dispersed in 80 minutes at a concentration 198 mg/L. Rats showed no toxic signs during exposure and 14 days thereafter. Body weight gain and the organ-to-body weight ratios of the exposed rats compared to the control rats were not significantly different. No exposure related histopathological changes were noted in tissues and organs.

Interpretation: Vapor presents no acute inhalation hazard from single short term exposure.

Interpretation of results:
practically nontoxic
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Acute vapor inhalation exposures of rats resulted experimentally in no deleterious effect. These results show that ethyl centralite has a low volatility and should present no hazard due to inhalation ot its vapors at room temperature. Also, if vapors are present, acute inhalation from a single exposure presemts no hazard.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
198 000 mg/m³
Quality of whole database:
The study is comparable to Guideline study with acceptable restrictions and has Klimish score 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:
21.11.-7.12.2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was carried out in accordance with internationally valid GLP principles.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Breeding farm VELAZ s.r.o., Koleč u Kladna, Czech Republic- Weight at study initiation: average-females: 213.9 g, average-males: 252.34 g- Housing: animal room with monitored conditions – one animal in one plastic cage- Diet (e.g. ad libitum): ST 1 BERGMAN – standard pelleted diet- Water (e.g. ad libitum): drinking tap water - Acclimation period: at least 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 22+/-3°C- Humidity (%): 30-70%- Air changes (per hr): approximately 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour darkSTUDY TIME SCHEDULEAnimal supply: 16. 11. 2011Experimental part of study: 21. 11. – 07. 12. 2011
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE- Area of exposure: 6x6 cm- % coverage: aprox. 10% of the body surface- Type of wrap if used: The application site was covered by mull and held in contact by plaster (strapping). REMOVAL OF TEST SUBSTANCE- Washing (if done): water- Time after start of exposure: 24 hrsTEST MATERIAL- Amount(s) applied (volume or weight with unit): according to its body weight and the dose (2000 mg/kg)- For solids, paste formed: no
Duration of exposure:
24 hrs
Doses:
2000 mg/kg bw.
No. of animals per sex per dose:
5 females and 5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing:- body weight:before application, 8th day of clinical observation and at the end of study (15th day)- mortality: daily- clinical signs: daily- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test substance did not cause death of animals.
Clinical signs:
No clinical signs of intoxication were observed.
Body weight:
In males and females, the weight increments were adequate to species and age of animals in the experiment.
Gross pathology:
No macroscopic changes were diagnosed during pathological examination in all animals.
Interpretation of results:
practically nontoxic
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
According to the results of the dermal toxicity study, the value of LD50 (dermal) of test substance, Centralit, for rats is higher than 2000 mg/kg of body weight.
Executive summary:

The test substance, Centralit, was tested for acute dermal toxicity using Wistar rats.

Testing was performed according to the Method B.3 Acute Toxicity (Dermal), Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008.

The study was performed as limit test: two groups of animals – 5 males and 5 females at the dose of 2000 mg/kg of body weight. The pre-test was performed with 1 male and 1 female from each group. After end exposure test substance of these pilot animals, the other animals of the group were dosed.

The test substance was applied on the shaved skin of the test animals in delivered form for 24 hours.

The test animals were observed 14 days after exposure test substance, afterwards they were sacrificed, and the necropsy for macroscopic examination of the organs was performed.

The test substance applied at the dose of 2000 mg/kg of body weight did not cause death of animals. No clinical signs of intoxication were observed. No macroscopic change was diagnosed during pathological examination of animals.

According to the results of study, the value of LD50 (dermal) of the test substance, Centralit, for rats of both sexes is higher than 2000 mg/kg of body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The study is a GLP compliant and has Klimish score 1.

Additional information

Justification for selection of acute toxicity – inhalation endpoint
Only one study available

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Based on the available data, the substance is classified as Acute Tox.4, H302.