Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
May to June 2005
Reliability:
1 (reliable without restriction)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
not specified
GLP compliance:
yes
Test type:
fixed dose procedure
Species:
rat
Strain:
Sprague-Dawley
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Interfauna Iberica
- Weight at study initiation: 214 - 228 g
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 30 - 70


IN-LIFE DATES: From: To: 27 April to 4 May 2005
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 ml/Kg
- Amount of vehicle (if gavage): 10 ml/Kg
- Lot/batch no. (if required): 607-18FEB2005


Doses:
300 mg/kg; 2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Sex:
not specified
Dose descriptor:
other: Not reported
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Según los resultados obtenidos en el Estudio y de acuerdo con el Sistema Armonizado Mundial (SAM) de clasificación y etiquetado de productos quimicos, el producto ensayado, se clasifica en la categoria 5 / No clasificado. Asimismo, y de acuerdo con el sistema actualmente utilizado en la Unión Europea (Directiva 2004/73/CE) y en los criterios publicados en el Diario Oficial de las Comunidades Europeas del 6 de agosto de 2001 (Directiva 2001/59/CE, Anexo VI) se concluye que el producto se considera No clasificado, por lo cual no es necesario asignarle notación de riesgo.
Executive summary:

Según los resultados obtenidos en el Estudio y de acuerdo con el Sistema Armonizado Mundial (SAM) de clasificación y etiquetado de productos quimicos, el producto ensayado, se clasifica en la categoria 5 / No clasificado. Asimismo, y de acuerdo con el sistema actualmente utilizado en la Unión Europea (Directiva 2004/73/CE) y en los criterios publicados en el Diario Oficial de las Comunidades Europeas del 6 de agosto de 2001 (Directiva 2001/59/CE, Anexo VI) se concluye que el producto se considera No clasificado, por lo cual no es necesario asignarle notación de riesgo.

 

No se registró mortalidad entre los animales tratados a la dosis de 2000 mg/kg.

 

La evolución del peso corporal medio de los animales tratados a la dosis de 2000 mg/kg fue normal. Sin embargo, en dos de las hembras se registró una ligera pérdida de peso corporal entre el primer y segundo dia del periodo de observación en el caso de una, y entre el segundo y séptimo dia en el caso de la otra hembra.

 

No se registraron alteraciones macroscopicas en las necropsias realizadas a todos los animales administrados a la dosis de 2000 mg/kg    

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 DAY
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: LACK OF CERTIFICATE
Qualifier:
no guideline followed
Principles of method if other than guideline:
Acute toxicity determined by single oral adminstration to rat.
GLP compliance:
yes
Test type:
acute toxic class method
Species:
rat
Strain:
other: rat Hsd. Brl:WH
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Harlan UK Ltd., Bicester
- Age at study initiation:4-6 weeks old
- Weight at study initiation:124-147 g
- Fasting period before study:overnight prior to test
- Housing:stainless steel mesh cages
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle:10%
- Amount of vehicle (if gavage):20ml/Kg
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED:135 g/l/2000 mg/kg

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
20 mL/kg
No. of animals per sex per dose:
2
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days (or other?)8 days
- Frequency of observations and weighing:day 1 and 8
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:weight gains between days 1 and 8
Sex:
male/female
Dose descriptor:
other: acute median and minimum lethal dose
Effect level:
> 2 000 mg/kg bw
Based on:
dissolved
Mortality:
none
Clinical signs:
none
Body weight:
Increased in each case
Gross pathology:
no effects
Other findings:
none
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Single oral administration of MEA Polyboate 1:3 135 g/L to a group of four fasted rats at a dose level of 2000 mg/kg had no adverse effects. Accordingly, the acute median lethal oral dose and the minmum lethal oral dose to rats was shown to exceed 2000mg/kg bodyweight.
Executive summary:

Two male and female fasted rats were dosed with MEA Polyboate 1:3 135g/L at 2000 mg/Kg on day 1. The test article was dispersed in purified water at a concentration of 10% m/v and administered by oral lavage at a dose volume of 20 mL/Kg. All animals were killed on Day 8 and subsequently underwent a terminal macroscopic examination.

No animal died. There were no clinical signs of systemic toxicity. All rats made substantial body weight gains between day 1 and day 8. No macroscopic changes were apparent at necroscopy on day 8.

Single oral administration of MEA Polyboate 1:3 135 g/L to a group of four fasted rats at a dose level of 2000 mg/kg had no adverse effects. Accordingly, the acute median lethal oral dose and the minimum lethal oral dose to rats was shown to exceed 2000mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
11 May 2017 - 30 May 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Species:
rat
Strain:
Wistar
Remarks:
Crl: WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
Source: Charles River UK, Kent, England
Outbred, SPF-quality
Young adult animals (approximately 10 weeks)
Weight at the Initiation of Dosing: 187 to 338 g.

On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) and following assignment to the study, animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.

The animals were allowed to acclimate to the Test Facility toxicology accommodation for at least 5 days before the commencement of dosing.
Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 21 to 22°C with an actual daily mean relative humidity of 43 to 69%. A 12 hour light/12 hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.

For psychological/environmental enrichment, animals were provided with paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom), except when interrupted by study procedures/activities.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
A single dose of test item was administered to the appropriate animals by dermal application on Day 1. One day before dosing, an area of approximately 5x7 cm on the back of the animals was clipped. The test item was applied in an area of approximately 10% of the total body surface, i.e. approximately 25 cm² for males and 18 cm² for females. The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Duration of exposure:
The application period was 24 hours, after which the dressing was removed and the skin cleaned of residual test item using water or an appropriate vehicle.
Doses:
The dose level was 2000 mg/kg body weight.
No. of animals per sex per dose:
5 males and 5 females (females were nulliparous and non-pregnant)
Control animals:
no
Details on study design:
Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day.

Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals during and for the first hour after dosing.

Animals were weighed individually on Day 1 (pre-dose), 8 and 15.

All moribund animals and animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One female was found dead on Day 2, no further mortality occurred.
Clinical signs:
Tremor, piloerection, red (snout), ptosis and/or hypothermia were noted for the majority of animals on Days 1 and/or 2.
Focal erythema, scales and/or scabs were seen in the treated skin-area of two males and one female. These local effects were considered not to have affected the conclusion of the study.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
Beginning autolysis was noted for the animal that died during the study, at macroscopic post mortem examination. Macroscopic post mortem examination of the other animals at termination did not reveal any abnormalities.

TABLE 1 MORTALITY DATA


 
TEST DAY
HOURS AFTER TREATMENT
 

 
1
0
 

 
1
2
 

 
1
4
 

 
2

 

 
3

 

 
4

 

 
5

 

 
6

 

 
7

 

 
8

 

 
9

 

 
10

 

 
11

 

 
12

 

 
13

 

 
14

 

 
15

 

'

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MALES 2000 MG/KG

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

FEMALES 2000 MG/KG

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

TABLE 2 CLINICAL SIGNS


 
TEST DAY
HOURS AFTER TREATMENT
 

 

MAX
GRADE
 

 
1
0

 

 
1
2

 

 
1
4

 

 
2

 

 
3

 

 
4

 

 
5

 

 
6

 

 
7

 

 
8

 

 
9

 

 
10

 

 
11

 

 
12

 

 
13

 

 
14

 

 
15

 

'


MALES 2000 MG/KG

ANIMAL 1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Piloerection

(1)

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

Various

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Ptosis

(3)

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 Red (Snout)

(1)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Erythema focal (Treated skin)

(4)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

Various

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Ptosis

(3)

1

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 3

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Piloerection

(1)

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 Scales (Flank right)

(3)

-

-

-

-

-

-

1

1

1

1

1

-

-

-

-

-

-

.

Various

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Ptosis

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 Red (Snout)

(1)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Erythema focal (Treated skin)

(4)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 Piloerection

(1)

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

.

Various

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Ptosis

(3)

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

No clinical signs noted

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.


FEMALES 2000 MG/KG

ANIMAL 6

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Piloerection

(1)

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

Various

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Ptosis

(3)

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 Red (Snout)

(1)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 7

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Piloerection

(1)

-

-

1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Various

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Ptosis

(3)

-

-

1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

ANIMAL 8

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Spasms

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Tremor

(3)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Piloerection

(1)

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

Various

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Ptosis

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 Hypothermia

(1)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 

- = sing not observed

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TABLE 2 CLINICAL SIGNS (continued)


 
TEST DAY
HOURS AFTER TREATMENT
 

 

MAX
GRADE
 

 
1
0

 

 
1
2

 

 
1
4

 

 
2

 

 
3

 

 
4

 

 
5

 

 
6

 

 
7

 

 
8

 

 
9

 

 
10

 

 
11

 

 
12

 

 
13

 

 
14

 

 
15

 

'


FEMALES 2000 MG/KG

ANIMAL 9

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Piloerection

(1)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

Various

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Ptosis

(3)

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 10

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Erythema focal (Treated skin)

(4)

-

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

.

 Piloerection

(1)

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 Scabs (Treated skin)

(3)

-

-

-

-

1

1

1

1

1

1

1

-

-

-

-

-

-

.

 

- = sign not observed

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TABLE 3 BODY WEIGHTS (GRAM)


 

 
SEX/DOSE LEVEL
 

 
ANIMAL
 

 
DAY 1
 

 
DAY 8
 

 
DAY 15
 

'


MALES 2000 MG/KG

 

 

1

301

299

324

.

 

2

321

336

360

.

 

3

313

321

351

.

 

4

323

321

343

.

 

5

338

347

378

.

 

 

 

 

 

.

 

MEAN

319

325

351

.

 

ST.DEV.

14

18

20

.

 

N

5

5

5

.

 

 

 

 

 

.


FEMALES 2000 MG/KG

 

 

6

217

218

240

.

 

7

185*

---

---

.

 

8

196

202

218

.

 

9

214

223

240

.

 

10

197

201

213

.

 

 

 

 

 

.

 

MEAN

202

211

228

.

 

ST.DEV.

13

11

14

.

 

N

5

4

4

.

 

 

 

 

 

.

* Animal was found dead on Day 2, terminal body weight was 189 grams.

 

 

 

TABLE 4 MACROSCOPIC FINDINGS


 
ANIMAL
 

 
ORGAN
 

 
FINDING
 

 
DAY OF DEATH
 

'


MALES 2000 MG/KG

1

 

No  findings noted

Scheduled necropsy

.

 

 

 

Day 15 after treatment

.

2

 

No  findings noted

Scheduled necropsy

.

 

 

 

Day 15 after treatment

.

3

 

No  findings noted

Scheduled necropsy

.

 

 

 

Day 15 after treatment

.

4

 

No  findings noted

Scheduled necropsy

.

 

 

 

Day 15 after treatment

.

5

 

No  findings noted

Scheduled necropsy

.

 

 

 

Day 15 after treatment

.


FEMALES 2000 MG/KG

6

 

No  findings noted

Scheduled necropsy

.

 

 

 

Day 15 after treatment

.

7

General observations

Beginning  autolysis.

Spontaneous death

.

 

 

 

Day 2 after treatment

.

8

 

No  findings noted

Scheduled necropsy

.

 

 

 

Day 15 after treatment

.

9

 

No  findings noted

Scheduled necropsy

.

 

 

 

Day 15 after treatment

.

10

 

No  findings noted

Scheduled necropsy

.

 

 

 

Day 15 after treatment

.

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of MEA Polyborate 1:3 in Wistar rats was established to exceed 2000 mg/kg body weight.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Additional information

Justification for classification or non-classification

Oral route: Single oral administration of MEA Polyboare 1:3 135 g/L to a group of four fasted rats at a dose level of 2000 mg/kg had no adverse effects. Accordingly, the acute median lethal oral dose and the minimum lethal oral dose to rats was shown to exceed 2000 mg/kg bodyweight. Therefore, the substance is not classified for acute toxicity oral route according to GHS.

Dermal route: The dermal LD50 value of MEA Polyborate 1:3 in Wistar rats was established to exceed 2000 mg/kg body weight, therefore the substance is not classified for acute toxicity dermal route according to GHS.