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Diss Factsheets

Administrative data

Description of key information

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approximately 2500 mg/kg bodyweight 
Acute dermal and acute inhalation studies were not conducted as the substance is classified as corrosive.

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:
The study was performed between 30 June 2011 and 26 July 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese MAFF, 2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS- Source: Female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK.- Age at study initiation: Eight to twelve weeks of age- Weight at study initiation: 158 - 183 g - Fasting period before study: Overnight fast immediately before dosing and for approximately three to four hours after dosing- Housing: The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes.- Diet (e.g. ad libitum): Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study.- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.- Acclimation period: At least five days.ENVIRONMENTAL CONDITIONS- Temperature (°C): Set to achieve limits of 19 to 25°C - Humidity (%): Set to achieve limits of 30 to 70%- Air changes (per hr): At least fifteen changes per hour - Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE- Concentration in vehicle: 30 mg/ml or 200 mg/mlMAXIMUM DOSE VOLUME APPLIED: 10 ml/kgDOSAGE PREPARATION: The test item was freshly prepared, as required, as a solution at the appropriate concentration 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. CLASS METHOD (if applicable)- Rationale for the selection of the starting dose: Using available information on the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Doses:
300 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
3 females at 300 mg/kg. 6 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days - Frequency of observations and weighing: 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. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.- Necropsy of survivors performed: yes; At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Sex:
female
Dose descriptor:
LD50
Effect level:
2 500 mg/kg bw
Based on:
test mat.
Mortality:
Individual mortality data are given in Table 1.One animal treated at a dose level of 2000 mg/kg was found dead two days after dosing.
Clinical signs:
other: Individual clinical observations are given in Table 2 and Table 3.Signs of systemic toxicity noted in one animal treated at a dose level of 2000 mg/kg were increased salivation, red/brown staining around the snout and noisy respiration. There were no oth
Gross pathology:
Individual necropsy findings are given in Table 6 and Table 7.Abnormalities noted at necropsy of the animal that died during the study were patchy pallor of the liver, dark spleen, dark kidneys and haemorrhage of the gastric mucosa. No other abnormalities were noted at necropsy of animals that were killed at the end of the study.

Table 1: Mortality Data

Dose Level mg/kg

Sex

Number of Animals Treated

Deaths During Day of Dosing
(Hours)

Deaths During Period After Dosing
(Days)

Deaths

½

1

2

4

1

2

3

4

5

6

7

8-14

300

Female

3

0

0

0

0

0

0

0

0

0

0

0

0

0/3

2000

Female

3

0

0

0

0

0

0

0

0

0

0

0

0

0/3

Female

3

0

0

0

0

0

1

0

0

0

0

0

0

1/3

Table 2: Individual Clinical Observations - 300 mg/kg

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

300

1-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0


0= No signs of systemic toxicity

Table 3: Individual Clinical Observations - 2000 mg/kg

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

2-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

SSs

SSs

S

Rn

Rn

Rn

Rn

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1

Female

0

0

0

0

0

X

 

 

 

 

 

 

 

 

 

 

 

 

3-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0


0= No signs of systemic toxicity           

Rn = Noisy respiration

S = Increased salivation

Ss = Red/brown staining around the snout

X = Animal dead

Table 4: Individual Bodyweights and Weekly Bodyweight Changes - 300 mg/kg

Dose Level

mg/kg

Animal Number
and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

300

1-0 Female

177

203

210

26

7

1-1 Female

158

173

180

15

7

1-2 Female

183

210

220

27

10

Table 5: Individual Bodyweights and Weekly Bodyweight Changes - 2000 mg/kg

Dose Level

mg/kg

Animal Number
and Sex

Bodyweight (g) at Day

Bodyweight (g) at Death

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

2-0 Female

177

182

193

 

5

11

2-1 Female

171

174

189

 

3

15

2-2 Female

169

177

191

 

8

14

3-0 Female

162

177

183

 

15

6

3-1 Female

158

-

-

150

-

-

3-2 Female

168

174

180

 

6

6

Table 6: Individual Necropsy Findings - 300 mg/kg

Dose Level

mg/kg

Animal Number and Sex

Time of Death

Macroscopic Observations

300

1-0 Female

Killed Day 14

No abnormalities detected

1-1 Female

Killed Day 14

No abnormalities detected

1-2 Female

Killed Day 14

No abnormalities detected

Table 7: Individual Necropsy Findings - 2000 mg/kg

Dose Level

mg/kg

Animal Number and Sex

Time of Death

Macroscopic Observations

2000

2-0 Female

Killed Day 14

No abnormalities detected

2-1 Female

Killed Day 14

No abnormalities detected

2-2 Female

Killed Day 14

No abnormalities detected

3-0 Female

Killed Day 14

No abnormalities detected

3-1 Female

Found Dead Day 2

Liver: patchy pallor

Spleen: dark

Kidneys: dark

Gastric mucosa: haemorrhagic

3-2 Female

Killed Day 14

No abnormalities detected

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria 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 approximately 2500 mg/kg bodyweight (Globally Harmonised Classification System - Category 5, >2000 - 5000 mg/kg bodyweight).
Executive summary:

Introduction.

The study was performed to assess the acute oral toxicity of the test item following a single oral administration in the Wistar strain rat. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001)

- Method B1 tris Acute Toxicity (Oral) of CommissionRegulation (EC) No. 440/2008

Method. 

A group of three fasted females was treated with the test item at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at a dose level 2000 mg/kg bodyweight. Dosing was performed sequentially.

The test item was administered orally as a solution in distilled water. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

One animal treated at a dose level of 2000 mg/kg was found dead two days after dosing. 

Clinical Observations. 

Signs of systemic toxicity noted in one animal treated at a dose level of 2000 mg/kg were increased salivation, red/brown staining around the snout and noisy respiration. There were no other signs of systemic toxicity noted.

Bodyweight. 

The surviving animals showed expected gains in bodyweight over the study period.

Necropsy. 

Abnormalities noted at necropsy of the animal that died during the study were patchy pallor of the liver, dark spleen, dark kidneys and haemorrhage of the gastric mucosa. No other abnormalities were noted at necropsy of animals that were killed at the end of the study.

Conclusion. 

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approximately 2500 mg/kg bodyweight (Globally Harmonised Classification System ‑ Category 5, >2000 ‑ 5000 mg/kg bodyweight).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw
Quality of whole database:
The submitted study is of sufficient quality for regulatory submission (Klimisch 1).

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute Oral Toxicity

A single key study of acute toxicity via the oral route of exposure is presented, the study was conducted in accordance with OECD Guideline 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001).

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approximately 2500 mg/kg bodyweight (Globally Harmonised Classification System ‑ Category 5, >2000 ‑ 5000 mg/kg bodyweight).

Acute Dermal/Inhalation Toxicity

Acute dermal and acute inhalation studies were not conducted as the substance is classified as corrosive.


Justification for selection of acute toxicity – oral endpoint
Key study, conducted in accordance with current OECD Guideline and in accordance with the principles of GLP.

Justification for classification or non-classification

The substance does not meet the criteria for classification, under the CLP regulations, for acute toxicity via the oral route based on the result of an acute oral toxicity study conducted to OECD Guideline 423, giving a LD50 of approximately 2500 mg/kg bodyweight.

The substance is classified as a corrosive and therefore no acute dermal or inhalation toxicity studies were conducted.

As a consequence no classification can be made for acute dermal toxicity. Dermal effects will be characterised by local tissue damage.

Systemic uptake via skin is likely to be limited and the low acute oral toxicity indicates a low systemic toxicity.

Acute inhalation toxicity information for classification is lacking, however testing is not justified as the exposure potential is considered to be low due to low vapour pressure.