Registration Dossier

Administrative data

Description of key information

The acute oral toxicity study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat. 
The acute inhalation toxicity study was to determine the acute inhalation toxicity of FAT 20341/A TE when administered for a single, 4-hour, nose-only inhalation exposure to rats.
The acute dermal toxicty study was performed to assess the acute dermal toxicity of the tets item, FAT 20341/A TE, in the Wistar starin rat.

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:
Study conducted between 25th February 2014 and 20th March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Female Wistar (RccHan™:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization 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. At the start of the study the animals were eight to twelve weeks of age. The body weight variation did not exceed ± 20% of the body weight of the initially dosed animal.

The animals were housed in groups of up to three in suspended 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 (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of 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 fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Test item preparation:
For the purpose of the study the test item was freshly prepared, as required, as a solution in distilled water.

The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Procedure:
Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.

Groups of fasted animals were treated as follows:

Dose Level (mg/kg) Concentration (mg/mL) Dose Volume (mL/kg) Number of Rats
2000 200 10 3
2000 200 10 3

Dosing:
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 the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.

Doses:
2000 mg/kg
No. of animals per sex per dose:
3 animals per dose group (all females)
Control animals:
no
Details on study design:
- Duration of observation period following administration:
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days.

- Frequency of observations and weighing:
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, necropsy.

Rats are the preferred species of choice as historically used for safety evaluation studies and are specified in the appropriate test guidelines.
Preliminary study:
Not applicable.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal was found dead one day after dosing. Please see table 1 for more information in the any other information on results section.
Clinical signs:
Clinical Observations. Signs of systemic toxicity noted in the animal that died during the study were hunched posture, lethargy, pilo erection and cyanosis. Diarrhea was noted in the second group of three animals. Blue stained urine and feces was noted in all animals. All visible skin and eyes of four animals were stained blue.
Body weight:
Body Weight. Surviving animals showed expected gains in body weight over the observation period, except for one animal which showed expected gain in body weight during the first week but body weight loss during the second week.
Gross pathology:
Necropsy findings:
Discoloration of the heart, lungs, liver, spleen, kidneys, gastric mucosa, non glandular epithelium of the stomach, small and large intestines and bladder and dark blue colored liquid present in the stomach were noted at necropsy of the animal that died during the study. Discoloration of the heart, liver, kidneys, gastric mucosa, non glandular epithelium of the stomach and small and large intestines were noted at necropsy of one animal that was killed at the end of the study. Discolored kidneys were noted at necropsy of two animals that were killed at the end of the study. No abnormalities were noted at necropsy of two animals that were killed at the end of the study. Please see table 2 in the any other information on results section for more details.

TABLES

Table 1     Individual Clinical Observations and Mortality Data

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Female

0

0UF

0UF

0UF

0UF

0F

0

0

0

0

0

0

0

0

0

0

0

0

1-1

Female

0

0UF

0UF

0UF

0UF

0F

0

0

0

0

0

0

0

0

0

0

0

0

1-2

Female

HL

HLPCyUF

HLCyUF

HPLUF#

X

 

 

 

 

 

 

 

 

 

 

 

 

 

2-0

Female

0

0

DUF

DUF

0UF#

0F#

0F#

0F#

0F#

0F#

0F#

0#

0#

0#

0#

0#

0#

0#

2-1

Female

0

0

DUF

DUF

0UF#

0F#

0F#

0F#

0F#

0F#

0F#

0

0

0

0

0

0

0

2-2

Female

0

0

DUF

DUF

DUF#

0F#

0F#

0F#

0F#

0F#

0F#

0#

0#

0#

0#

0#

0#

0#



0= No signs of systemic toxicity      H = Hunched posture                        L = Lethargy        P = Pilo‑erection                 Cy = Cyanosis           D = Diarrhea

F= Faeces stained dark blue             U =Blue stained urine                       # = Skin and eyes stained blue                        X = Animal dead

Table 2     Individual Necropsy Findings:

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

1-0 Female

Killed Day 14

No abnormalities detected

1-1 Female

Killed Day 14

No abnormalities detected

1-2 Female

Found dead Day 1

Heart: discolored

Lungs: discolored

Liver: discolored

Spleen: discolored

Kidneys: discolored

Stomach: dark blue colored liquid present

Gastric mucosa: discolored

Non-glandular epithelium of the stomach: discolored

Small intestine: discolored

Large intestine: discolored

Bladder: discolored

2-0 Female

Killed Day 14

Heart: discolored

Liver: discolored

Kidneys: discolored

Gastric mucosa: discolored

Non-glandular epithelium of the stomach: discolored

Small intestine: discolored

Large intestine: discolored

2-1 Female

Killed Day 14

Kidneys: discolored

2-2 Female

Killed Day 14

Kidneys: discolored

 

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 item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Category 5, >2000 – 5000 mg/kg body weight).

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

Introduction:

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

 

Methods:

A group of three fasted females was treated with the test item at a dose level of 2000 mg/kg body weight. This was followed by a further group of three fasted females at the same dose level. Dosing was performed sequentially.

 

The test item was administered orally as asolutionindistilled water. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

 

Results:

Mortality. One animal was found dead one day after dosing.

 

Clinical Observations. Signs of systemic toxicity noted in the animal that died during the study were hunched posture, lethargy, pilo‑erection and cyanosis. Diarrhea was noted in the second group of three animals. Blue stained urine and feces was noted in all animals. All visible skin and eyes of four animals were stained blue.

 

Body Weight. Surviving animals showed expected gains in body weight over the observation period, except for one animal which showed expected gain in body weight during the first week but body weight loss during the second week.

 

Necropsy. Discoloration of the heart, lungs, liver, spleen, kidneys, gastric mucosa, non‑glandular epithelium of the stomach, small and large intestines and bladder and dark blue colored liquid present in the stomach were noted at necropsy of the animal that died during the study. Discoloration of the heart, liver, kidneys, gastric mucosa, non‑glandular epithelium of the stomach and small and large intestines were noted at necropsy of one animal that was killed at the end of the study. Discolored kidneys were noted at necropsy of two animals that were killed at the end of the study. No abnormalities were noted at necropsy of two animals that were killed at the end of the study.

Conclusion:

The acute oral median lethal dose (LD50) of teh test item in the female Wistar strain rat was astimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Category 5, >2000 - 5000 mg/kg body weight).

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study 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:
April 2015 - May 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is performed according to OECD/US EPA OPPTS guidelines and according GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
September 2009
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC, USA
- Age at study initiation: 8 weeks
- Weight at study initiation: males 254 g to 283 g; females 195 g to 217 g
- Fasting period before study: no
- Housing: all animals were housed individually in suspended wire-mesh cages. On the day of exposure, the animals were placed in nose-only exposure holding tubes in the animal room, transported to the exposure room, exposed for the requisite duration then returned to their home cages.
- Diet: PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002 (block) ad libitum, except during acclimation to the nose-only restraint and during the exposure period.
- Water: Reverse osmosis-treated water supplying the facility) ad libitum, except during acclimation to the nose-only restraint and during the exposure period
- Acclimation period: a minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4 to 21.7
- Humidity (%): 43.4 to 51.3
- Air changes (per hr): a minimum of 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 05 May 2015 To: 19 May 2015
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a stainless steel, conventional nose-only exposure system with rubber grommets in exposure ports to engage the animal holding tubes
- Exposure chamber volume: 7.9-L
- Method of holding animals in test chamber: animals were restrained in nose-only exposure holding tubes during exposure
- Source and rate of air: airflow rates through the exposure system were calculated from the airflow required for aerosol generation and provided a minimum of 12 air changes per hour through the exposure system
- Method of conditioning air: airflow to the exposure system was provided using a dry, breathing quality, in-house, compressed air source. A temperature and relative humidity transmitter probe (model no. HX94C, Omega Engineering, Inc., Stamford, CT) was used with a display unit to monitor temperature and percent relative humidity.
- System of generating particulates/aerosols: The test substance was delivered at a constant rate to a jet mill air micronizer using an auger-type dry material feeder. The Accurate feeder was equipped with two Syntron Vibrators and a ½-inch solid core auger. Dry compressed air was supplied to the micronizing and inlet ports of the jet mill to affect aerosolization of the test substance using 2 regulators. The resulting aerosol from the jet mill was delivered to a 2-inch PVC elbow fitting (position downward) located approximately 11-inches from the bottom of a 4-inch × 44-inch PVC pipe set. This settling pipe was in a vertical orientation to remove large particles from the aerosol atmosphere. The test substance atmosphere was delivered from the top of the settling pipe to a glass cyclone to further reduce particle size. From the cyclone, test substance atmosphere was directed to the nose-only exposure system through 22-mm corrugated respiratory tubing.
- Method of particle size determination: two aerosol particle size measurements were conducted during the exposure using a 7-stage stainless-steel cascade impactor. Pre weighed, 22-mm stainless-steel collection substrates were used as the collection substrates for stages 1 through 7 and a 25-mm glass-fiber filter (Type A/E, PALL Corporation) was used as the collection substrate for the final stage. Samples were collected at approximately 0.9 L/minute for 1.5 minutes. The filters were re-weighed and the particle size was calculated based on the impactor stage cut-offs. The aerosol size was expressed as the MMAD and the GSD.
- Treatment of exhaust air: exhaust atmosphere was filtered using a Solberg filter prior to entering the facility exhaust system, which includes redundant exhaust blowers preceded by activated-charcoal and HEPA-filtration units.
- Temperature, humidity, pressure in air chamber: 19°C, 18%, airflow rate 60.7 L/min


TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.5 / 3.13
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1.3 mg/L (Maximum Attainable Concentration, MAC)
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation for mortality twice daily, observations for clinical signs one approximately 1 to 2 hours following exposure and once daily thereafter, body weights were measured prior to exposure (day 0) and on exposure days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes: the major organ systems of the cranial, thoracic, and abdominal cavities were examined for all animals.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.3 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: 1.3 mg/L is Maximum Attainable Concentration
Mortality:
Mortality was 0/10 animals for the 1.3 mg/L group.
Clinical signs:
other: Significant clinical observations immediately following exposure included rales for 3 males and 4 females and labored respiration rate for 1 female. Significant clinical observations at the 1 to 2 hours post-exposure observation period included rales for
Body weight:
From study day 0 to 1, all males lost 12 to 41 grams and all females lost 7 to 24 grams. All animals surpassed their initial (study day 0) body weight by study day 14 and were considered normal.
Initial body weight decrement followed by body weight gain during the 14-day observation period is common for animals exposed to a dust aerosol for 4 hours by nose-only inhalation.
Gross pathology:
The following macroscopic findings were recorded at the scheduled necropsy:
Blue Discoloration of the Lungs (4m/4f), Blue Discoloration of the Trachea (1m), Blue Discoloration on the Skin (2m/5f), Blue Discoloration on the Tail (4m/5f), Blue Discoloration on the Testes (2m).

nominal concentration data:

Group

Test Substance Used

Exposure Time

Nominal Concentration

(mg/L)

(g)

(minutes)

(mg/L)

1.3

304

240

20.9

Mean actual exposure concentration:

Group (mg/L):

1.3

Target Exposure Concentration (mg/L):

1.0

Mean Exposure Concentration (mg/L):

1.3

Standard Deviation:

0.34

N:

7

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, the LC50 of FAT 20341/A TE was greater than the MAC (Maximum Attainable Concentration; 1.3 mg/L), with a particle size <4 µm, when male and female Crl:CD(SD) albino rats were exposed to a dust aerosol of the test substance as a single, 4-hour, nose-only exposure.
Executive summary:

Acute inhalation toxicity of FAT 20341/A TE was studied according to OECD 403. The test substance was administered to 1 group of 5 male and 5 female rats via 4 hours nose-only inhalation exposure as a dust aerosol at a concentration of 1.3 mg/L, the Maximum Attainable Concentration (MAC) with a particle size <4 µm. The aerosol exposure atmosphere was characterized by a mean particle size of 2.5 ± 3.13 µm (MMAD ± GSD). None of the animals died during exposure or during the 14-day post-exposure observation period. Significant clinical observations immediately following exposure included rales and labored respiration rate. Significant clinical observation at the 1 to 2 hours post-exposure observation period included rales, rapid respiration rate, labored respiration rate, increased respiration rate, and hypoactivity. Significant clinical observations for the surviving animals during the 14-day post-exposure observation period included rales, increased respiration rate, partial closure of the eyes, small feces, and decreased defecation and urination. All animals lost weight from study day 0 to 1. All animals surpassed their initial body (study day 0) weight by study day 14. Macroscopic findings noted for animals at the scheduled necropsy were blue discoloration of the lungs, trachea, skin, tail, and testes.

Based on the results of this study, the LC50of FAT 20341/A TE was greater than the MAC (Maximum Attainable Concentration; 1.3 mg/L), with a particle size <4 µm, when male and femaleCrl:CD(SD)albino rats were exposed to a dust aerosol of the test substance as a single, 4‑hour, nose-only exposure. In accordance with the CLP Regulation FAT 20341/A TE needs not to be classified for acute inhalation toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 300 mg/m³
Quality of whole database:
Study Klimisch 1.

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:
study conducted between 26th February 2014 and 12th March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
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 male and five female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization 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. At the start of the study the animals weighed at least 200 g, and were eight to twelve 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 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 (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of 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 fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Justification for choice of species:
Rats are the preferred species of choice as historically used for safety evaluation studies and are specified in the appropriate test guidelines.

Type of coverage:
semiocclusive
Vehicle:
other: moistened with distilled water
Details on dermal exposure:
Procedure:
On the day before treatment the back and flanks of each animal were clipped free of hair.

Using available information on the toxicity of the test item, a group of five male and five female rats was treated with the test item at a dose level of 2000 mg/kg.

The appropriate amount of test item, moistened with distilled water, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. 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.

After the 24 Hour 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 remainder of the study period.

Duration of exposure:
24 hours
Doses:
2000 mg /kg body weight
No. of animals per sex per dose:
5 males and 5 females were dosed at 2000 mg/kg bw
Control animals:
not required
Details on study design:
After the 24 Hour 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 remainder of the study period.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

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:

EVALUATION OF SKIN REACTIONS

Erythema and Eschar Formation Value

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) 4

Oedema Formation

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Any other skin reactions, if present were also recorded.

Individual body weights 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 thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.


Statistics:
No statistical analysis was performed.
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 95% confidence limits not reported.
Mortality:
No deaths occurred during the study.


Clinical signs:
There were no signs of systemic toxicity.
Body weight:
Animals showed expected gains in body weight, except for two males which showed expected gain in body weight during the first week but body weight loss during the second week.
Gross pathology:
No abnormalities were noted at necropsy. Necropsy readings can be found in table 1 for more males and in table 2 for females. Please note the tables can be found in the any other information on results section.
Other findings:
Dermal Irritation. A hardened light brown colored scab was noted at the test site of one female. There were no signs of dermal irritation noted at the test sites of the remaining animals.

Table 1     Individual Dermal Reactions - Males

Dose Level mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Male

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STA

STA

STA

STA

STA

STA

STA

0

0

0

0

0

1-1

Male

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STA

STA

STA

STA

STA

0

0

0

0

0

0

0

1-2

Male

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STA

STA

STA

STA

STA

0

0

0

0

0

0

0

1-3

Male

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STA

STA

STA

0

0

0

0

0

0

0

0

0

1-4

Male

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STA

STA

STA

STA

0

0

0

0

0

0

0

0


0=         No reactions

STA=      Blue colored staining

Table 2     Individual Dermal Reactions - Females

Dose Level mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0

Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STA

STA

STA

STA

STA

STA

0

0

0

0

0

0

2-1

Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STA

STA

STA

STA

STA

STA

0

0

0

0

0

0

2-2

Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STA

STA

STA

STA

STA

0

0

0

0

0

0

0

2-3

Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STASp

STASp

STASp

STASp

STASp

STA

STA

0

0

0

0

0

2-4

Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

STA

STA

STA

STA

STA

STA

STA

0

0

0

0

0

0

0


0=         No reactions

STA=      Blue colored staining

Sp=        Hardened light brown coloured scab

Interpretation of results:
not classified
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 body weight.

The test item does not meet the criteria for classification according to the Regulation (EC) No 1272/2008, relating to the Classification, Labeling and Packaging of Substances and Mixtures.


Executive summary:

Introduction:

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat.

 

Methods:

A group of ten animals (five males and five females) was given a single, 24 hour, semi‑occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

  

Results:

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. A hardened light brown colored scab was noted at the test site of one female. There were no signs of dermal irritation noted at the test sites of the remaining animals.

Body Weight. Animals showed expected gains in body weight, except for two males which showed expected gain in body weight during the first week but body weight loss during the second week.

Necropsy. No abnormalities were noted at necropsy.

 

Conclusion:

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 body weight.

 

The test item does not meet the criteria for classification according to the Regulation (EC) No 1272/2008, relating to the Classification, Labeling and Packaging of Substances and Mixtures.

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

Additional information

The first study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

The acute oral median lethal dose (LD50) of FAT 20341/A TE in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

The test item does not meet the criteria for classification according to the Regulation (EC) No 1272/2008, relating to the Classification, Labeling and Packaging of Substances and Mixtures.

The second study was performed to assess the acute inhalation toxicity of the test item in the Crl:CD(SD) strain rat.

the LC50 of FAT 20341/A TE was greater than the MAC (Maximum Attainable Concentration; 1.3 mg/L), with a particle size <4 μm, when male and female Crl:CD(SD) albino rats were exposed to an aerosol of the test substance as a single, 4-hour, nose-only exposure. Because LC50> MAC and none of the animals died during test, the substance does not need to be classified.

The third study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat.

The acute dermal median lethal dose (LD50) of FAT 20341/A TE in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.


Justification for selection of acute toxicity – oral endpoint
Only this study is available.

Justification for selection of acute toxicity – inhalation endpoint
Only this study is available.

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

Justification for classification or non-classification

Based on the above mentioned results the substance does not need to be classified according to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).