Registration Dossier

Administrative data

Description of key information

The registered substance was tested by the oral and inhalation routes.

In a single key study, conducted according to EC method B.1 and in compliance with GLP, no mortality was observed at the oral limit dose of 2000 mg/kg bw in males and females. The main clinical signs included reduced activity, and a hunched posture after dosing, then ataxia at 24 hours.

By inhalation, in the selected key study conducted according to OECD guideline 403 and EC method B.2, the LC50 was found to be above 23 mg/L (> 0.023 mg/m3 ; > 1238 ppm). No mortality was observed at that dose but animals showed decreased activity until day 5. At the next higher dose (2576 ppm ; 46.31 mg/L) , all animals were comatose following the dosing (first day), then most animals showed transient reduced activity and loss of reflex in the following days. Some animals were sacrificed during the observation period due to severe clinical signs. Another acute inhalation study was not used to determine the LC50 due to some technical deficiencies, however, similar clinical signs were observed, supporting GHS classification for narcotic effects.

A single key study, conducted according to OECD 402 and in compliance with GLP, no mortality was observed at the dermal limit dose of 2000 mg/kg bw in males and females. No clinical signs and no local skin reactions were noted during the study.

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:
03-MAY-1994 to 13-SEP-1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
This GLP-compliant study was conducted according to an EC method equivalent to OECD guideline 401 (Commission Directive 92/69/EEC).
Qualifier:
equivalent or similar 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
Specific details on test material used for the study:
Red liquid, no purity stated.

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 17338/35

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambien conditions, away from light
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Healthy outbred albino rats derived from the Sprague-Dawley strain (CD(SD)BR)
- Source: Charles River Italia S.p.A., Calco (Como), Italy
- Age at study initiation: 5 to 6 weeks (with female animals nulliparous and non-pregnant)
- Weight at study initiation: 126 to 150 g
- Fasting period before study: overnight fast prior to dosing (and a period of approximately 4 hrs following dosing)
- Housing: in group of 5 of one sex, in polycarbonate cages measuring 59x39x20 cm and equipped with a stainless steel mesh lid and floor; each cage was identified by a colour coded label recording the study number, animal number and the details of treatment.
- Diet: ad libitum, via a commercially available laboratory rodent diet (Altromin MT, A. Riper S.p.A., Bolzano, Italy)
- Water: ad libitum, via water bottle
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25°C
- Humidity: 30 to 70%
- Air changes: no data available
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From 05-MAY-1994 to 26-MAY-1994
Route of administration:
oral: gavage
Vehicle:
other: Alembicol D (fractionated coconut oil)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle, lot/batch no., purity: no data available
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: throughout the study, mortality was checked at the start of each working day and again in the afternoon to look for dead or moribund animals. However, at weekends the final check was carried out at approximately mid-day to allow for necessary necropsy examinations to be made the same day. In addition, all animals were weighed the day before dosing, at allocation to the study, immediately prior to dosing (day 1) and at weekly intervals (days 8 and 15).
- Necropsy of survivors performed: yes; all animals were killed on day 15 by carbon dioxide narcosis.
- Other examinations performed: clinical signs (immediately upon dosing, approximately 1, 2 and 4 hrs after dosing and daily thereafter for a total of 14 days)
Statistics:
When a formal assessment of the LD50 was undertaken, the mortality data generated was subjected to analysis. Suitable statistical methods were used to provide an estimate of the median lethal dose and slope of the dose-response curve with, where possible, confidence limits to the estimation.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the 14-day observation period following dosing.
Clinical signs:
Reduced activity, a hunched posture and production of mucoid faeces were observed in all animals (5M, 5F) on the day of dosing, 4 hours after administration. At 24 hours post-dosing, ataxia was noted in 2 males and 2 females, and a hunched posture in 2 females. In females, hair loss from the dorsal surfaces (day 3 to 15), skin/fur staining (day 3 to 11), and piloerection in males and females (day 9 to 13) were apparent during the remaining post-dose observation period.
Body weight:
Changes in body weight observed during the period of the study were within the range expected for this strain and age of animal.
Gross pathology:
No significant abnormalities were found at necropsy, findings being limited to the hair loss in-life.
Interpretation of results:
GHS criteria not met
Conclusions:
The results of this study indicated that the test substance had no significant toxic effect in male and female albino rats following oral administration of a single dose at a level of 2000 mg/kg.
Executive summary:

The acute oral toxicity of the test substance was investigated in the albino rat according to a protocol equivalent to OECD guideline 401 and in compliance with good laboratory practices (GLP).

 

A single dose of 2000 mg/kg (in Alembicol) was orally administered by gavage to male and female rats (5/group and sex). Animals were observed for a total of 14 days post-dose. Rats were then killed and subjected to necropsy examination.

 

No mortality occurred. Clinical signs observed after dosing included ataxia, a hunched posture, reduced activity, mucoid faeces, skin/fur staining, hair loss and piloerection. Changes in body weight were unremarkable. Necropsy revealed no significant abnormalities.

 

As a consequence, the oral LD50 of the test substance in rats was higher than 2000 mg/kg, therefore warranting no classification for this substance.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
19-APR-2001 to 30-MAY-2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not applicable
Remarks:
The 1981 guideline did not require to stagger the doses as in the current guideline. The fact that exposure to the different concentrations was not delayed does not constitute a deviation that would have an impact on the conclusions of the study.
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: batch 1/2000
- Expiration date of the lot/batch: march 2013

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient temperature in the dark


Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Alpk:APfSD (Wistar-derived) rats (20 males and 20 females, plus 6 spare males)
- Source: Rodent Breeding Unit (UK)
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: 298 to 342 g for males; 226 to 264 g for females
- Fasting period before study: yes
- Housing: 5 per cage, sexes separately; additional animals were housed 3 per cage.
- Diet: ad libitum, except during exposure (diet (RMI) supplied by Special Diet Services Limited (UK))
- Water: ad libitum, except during exposure
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 30 to 70%
- Air changes: at least 15 air changes per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From 22-MAY-2001 to 18-OCT-2001
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: polycarbonate tubes inserted into a PERSPEX exposure chamber covered with an aluminium cone and stood on an aluminium base.
- Exposure chamber volume: internal volume of ca. 27.6 L
- Method of holding animals in test chamber: animals were restrained in polycarbonate tubes supplied by Battelle (Switzerland).
- Source and rate of air: clean, dry air was passed at a nominal flow rate of 30 L/min (at normal temperature and pressure) at a concentration of 63.5 ppm and 20 L/min at a concentration of 613, 1275, or 2576 ppm. Air flows were monitored continuously and recorded at least 3 times using variable area flowmeters (KDG Flowmeters, UK).
- Method of conditioning air: air was dried and filtered using equipment supplied by Atlas-Copco (Sweden).
- System of generating particulates/aerosols: each test atmosphere was generated using a jacketed glass condenser. The test substance was pumped to the condenser using a Watson Marlow peristaltic pump. Before exposure of the test animals, the atmosphere was shown to be acceptably stable over ca. 30 min.
- Method of particle size determination: not applicable
- Treatment of exhaust air: no data available
- Temperature, humidity, pressure in air chamber: 12 air changes per hr; the temperature and relative humidity in each chamber were recorded at least 3 times during exposure using a portable, digital temperature and relative humidity monitor: they were within the range of 20.6 to 21.5°C and 5 to 44%, respectively.

TEST ATMOSPHERE
- Brief description of analytical method used: the atmospheric concentration of the test substance was determined for each exposure concentration by analysis of the material collected using a gas tight syringe (see in Table 1 below for details).
- Samples taken from breathing zone: test atmospheres were sampled from a front-facing port of the relevant exposure chamber, using a 5-mL gas-tight syringe equipped with an integral on-off valve and detachable sampling probe.

VEHICLE
- Composition of vehicle, concentration of test material in vehicle, justification of choice of vehicle, lot/batch no., purity: not applicable

- Rationale for the selection of concentrations: atmospheric concentrations of 50, 500, or 2500 ppm were selected on the basis of the results of trial exposures at 250 and 2000 ppm (3 males in both trials). In addition, a further concentration of 1275 ppm was carried out to meet specific safety labelling criteria.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
target : 50, 500, 1275, 2500 ppm (i.e. equivalent to 0.93, 9.26, 23.62, 46.31 mg/L)
achieved: 63.5, 613, 1238, 2576 ppm
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: see below
- Necropsy of survivors performed: yes
- Other examinations performed:
* Clinical signs: during exposure, animals were observed frequently. At the end of the 4-hour exposure period, each rat was given a detailed clinical examination. The animals were also given detailed clinical observations, (including the finding of "no abnormalities detected"), daily during the 14-day observation period.
* Body weight: the body weight of each rat was recorded on day -1 (to ensure animals of one sex were within a similar weight range), 1, 8 and prior to termination on day 15.
* Macroscopic examination: all animals were examined post mortem. This involved an external observation and an internal examination of all thoracic and abdominal viscera.
Preliminary study:
Two preliminary groups, of 3 males each, were used for trial. A first group (animals A-C) was exposed to a target concentration of 250 ppm for periods of 1, 2 or 4 hours respectively. The second group (animals D-F) was exposed to a target concentration of 2000 ppm for periods of 1, 2 or 4 hours, respectively.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 238 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: The LC50 (lower and upper confidence limits) and slope of the regression lines could not be calculated from the data but the LC50 was estimated to be higher than 1238 ppm (i.e., 23 mg/L).
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 23 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: converted from 1238 ppm
Mortality:
There were no deaths in animals in the 63.5-, 613-, 1238-ppm group during the exposure or observation periods. Animals in the 2576-ppm group survived the exposure period but some animals were killed following exposure due to severe clinical effects (see in Table 2 below for details).
Clinical signs:
other: - DURING EXPOSURE: Wet fur was observed in all animals (an abnormality generally associated with restraint). Some animals exposed to 63.5 or 613 ppm had stains around the snout. There were no other clinical changes at these dose levels. Animals exposed to
Body weight:
At an exposure concentration of 63.5 ppm, all gained weight to the end of the study. At an exposure concentration of 613 ppm, all animals were gaining weight by day 15 of the study. At an exposure concentration of 1238 ppm, 2 females had gained a small amount of weight by day 15 of the study but the body weights of the remaining animals were equal to or below their initial body weight. At an exposure concentration of 2576 ppm, 1 female had gained weight on day 15 of the study but the body weights of the other surviving male and female were below their initial weight on day 15 of the study.
Gross pathology:
At an exposure concentration of 2576 ppm, some males had stained eyelids and stains around the nose and mouth. At an exposure concentration of 1238 ppm, 1/5 females and 5/5 males had a mass at the base of the tail from day 13 to 15. In the absence of similar findings in the highest dose and clear compound-related effects, the significance of this observation remains unclear.

Table 2: Mortality

Group

Analytical concentration (ppm)

Died or killed in extremis

Day of death

1

63.5

0

NA

2

613

0

NA

4

1238

0

NA

3

2576

4 males

3 females

6 (2 animals), 7 and 8

2, 3 and 8

Table 3: Clinical observations immediately after exposure

 

Table 2: Mortality

Group

Analytical concentration (ppm)

Died or killed in extremis

Day of death

1

2

4

3

 

63.5

613

1238

2576

 

0

0

0

4 males

3 females

NA

NA

NA

6 (2 animals), 7 and 8

2, 3 and 8

 

 

Table 3: Clinical observations immediately after exposure

Clinical observation

Analytical concentrations (ppm)

Incidence in males

Incidence in females

Lachrymation

63.5

2/5

1/5

613

0/5

1/5

1238

-

-

2576

0/5

0/5

Wet fur

63.5

5/5

5/5

613

5/5

5/5

1238

5/5

5/5

2576

5/5

5/5

Stains around nose

63.5

2/5

1/5

613

5/5

1/5

1238

-

-

2576

-

-

Piloerection

63.5

-

-

613

3/5

5/5

1238

3/5

4/5

2576

-

-

Salivation

63.5

-

-

613

2/5

0/5

1238

5/5

5/5

2576

5/5

5/5

Coat stained

63.5

-

-

613

4/5

2/5

1238

-

-

2576

-

-

Activity decreased

63.5

-

-

613

-

-

1238

5/5

5/5

2576

-

-

Breathing depth increased

63.5

-

-

613

-

-

1238

5/5

5/5

2576

5/5

5/5

Breathing rate decreased

63.5

-

-

613

-

-

1238

5/5

5/5

2576

5/5

5/5

Cold

63.5

-

-

613

-

-

1238

5/5

5/5

2576

5/5

5/5

Reduced foot withdrawal reflex

63.5

-

-

613

-

-

1238

5/5

5/5

2576

5/5

5/5

Palpebral reflex absent

63.5

-

-

613

-

-

1238

1/5

1/5

2576

5/5

5/5

Pinna reflex absent

63.5

-

-

613

-

-

1238

3/5

2/5

2576

5/5

5/5

Prostrated

63.5

-

-

613

-

-

1238

5/5

4/5

2576

-

-

Reduced righting reflex

63.5

-

-

613

-

-

1238

5/5

5/5

2576

-

-

Reduced response to sound

63.5

-

-

613

-

-

1238

5/5

5/5

2576

-

-

Decreased visual placement response

63.5

-

-

613

-

-

1238

5/5

5/5

2576

5/5

5/5

Gasping

63.5

-

-

613

-

-

1238

0/5

1/5

2576

3/5

3/5

Increased response to touch

63.5

-

-

613

-

-

1238

5/5

5/5

2576

-

-

Comatose

63.5

-

-

613

-

-

1238

-

-

2576

5/5

5/5

Abnormal respiratory noise

63.5

-

-

613

-

-

1238

-

-

2576

1/5

3/5

Interpretation of results:
GHS criteria not met
Remarks:
LC50 > 20 mg/L
Conclusions:
Nose-only exposure to vapours of the test substance at a concentration of 1238 ppm resulted in no deaths. It was thus concluded that the LC50 of the test substance was higher than 1238 ppm (or 23 mg/L) for male and female rats.
Executive summary:

This acute inhalation toxicity study was conducted according to OECD guideline 403 and in compliance with good laboratory practices (GLP).

Groups of five male and five female Alpk:APfSD (Wistar-derived) rats were exposed nose-only for a single 4-hour period to a vapour of the test substance at target concentrations of 50 ppm, 500, 1275, or 2500 ppm. Test atmospheres were analysed for vapour concentration. Following exposure, the animals were retained without treatment for 14 days. Clinical observations and body weights were recorded throughout the study and at the end of the schedule period, the animals were killed and given a gross examination post-mortem.

 

The achieved test atmospheres had the following characteristics:

 

Target

concentration

(ppm)

Achieved

concentration

(ppm)

2500

2576

1275

1238

500

613

50

63.5

 

At an exposure concentration of 2576 ppm, 4 males and 3 females died during the maintenance period. Of the 3 surviving animals only 1 female regained its initial body weight by day 15 of the study. There were a number of clinical changes indicative of both respiratory irritation and general toxicity including comatose state in all males and females on the first day, reduced activity days 3 to 6 in most animals, loss of reflex, which generally persisted until termination in one or more animals. There were some minor macroscopic changes.

 

At an exposure concentration of 1238 ppm, there were no mortalities. Two females had exceeded their initial body weights by day 15 of the study but the body weights of the remaining animals were equal to or below their initial body weights by day 15 of the study. There were a number of clinical changes indicative of both respiratory irritation and general toxicity, including decreased activity (day 1 to 5) which had resolved by day 12 of the maintenance period. There were no compound-related macroscopic changes.

 

At an exposure concentration of 613 ppm there were no mortalities. All animals were gaining weight by day 15 of the study. There were minimal clinical changes which had resolved by day 3 of the study and no macroscopic changes.

 

At an exposure concentration of 63.5 ppm there were no mortalities, no effects on body weight, minimal clinical changes which had resolved by day 3 of the study and no macroscopic changes.

 

Nose-only exposure for 4 hours to the test substance at a concentration of 1238 ppm resulted in no deaths. It was thus concluded that under the conditions of this study the LC50 of the test substance was higher than 1238 ppm (23 mg/L) for male and female rats, therefore the test substance does not meet the classification criteria of EC Regulation No. 1272/2008 (CLP / EU GHS) for acute inhalation toxicity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
0.023 mg/m³

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:
03-AUG-2017 to 15-JAN-2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Temperature values and relative humidity values outside the expected ranges were recorded during the study. These deviations have no presumed impact on the outcome or integrity of the study
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
Temperature values and relative humidity values outside the expected ranges were recorded during the study. These deviations have no presumed impact on the outcome or integrity of the study
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: BLT 03-2017
- Expiration date of the lot/batch: March 2022
- Purity test date: 10 March 2017
Species:
rat
Strain:
Wistar
Remarks:
CRL:(WI)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adults
- Weight at study initiation: 218 to 242g
- Fasting period before study: no
- Housing: Individual caging in Type II. polypropylene/polycarbonate cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 - 28.7 °C
- Humidity (%): 32 - 75 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 08-AUG-2017 To: 22-AUG-2017
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: approximately 10 % area of the total body surface
- Type of wrap if used: gauze pad maintained with adhesive hypoallergenic plaster. The entire trunk of the animals was then wrapped with semi occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water at body temperature
- Time after start of exposure: 24 hrs



Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
> The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs were observed after treatment with the test item or during the 14-day observation period.
No local dermal signs were observed after treatment with the test item during the 14-day observation period.
Body weight:
No effects were observed on body weights or body weight gains in any animal during the study.
Gross pathology:
No specific observations at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test item 1,4-Diiodoperfluorobutane was found to be higher than 2000 mg/kg bw in male and female Wistar rats.
Executive summary:

The acute dermal toxicity of 1,4-Diiodoperfluorobutane was investigated in CRL:(WI) rats, in compliance with OECD Guideline No.: 402.

A limit test was carried out at 2000 mg/kg body weight in both sexes (5 rats/sex). The test item was applied as supplied as a single dermal 24-hour exposure under a semi-occlusive dressing, followed by a 14-day observation period.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Gross macroscopic examination performed on all animals at the end of the 2-week observation period (Day 14).

There was no mortality during the study. No clinical signs and no local dermal signs were observed after treatment with the test item or during the 14-day observation period. No effects were observed on body weights or body weight gains in any animal during the study. There was no evidence of abnormalities at necropsy.

 

The acute dermal median lethal dose (LD50) of the test item 1,4-Diiodoperfluorobutane was found to be higher than 2000 mg/kg bw in male and female Wistar rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

Based on the results of good quality GLP studies, and acute oral LD50 > 2000 mg/kg bw, an acute inhalation LC50 > 20 mg/L, and an acute dermal LD50 > 2000 mg/kg bw the substance is not classified for acute toxicity effects. However, based on transient effects observed following administration of the high doses, especially by inhalation, the substance is classified for narcotic effects, STOT SE3, with the hazard phrase H336, May cause drowsiness or dizziness.