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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
The study was performed between 21 April 2010 and 01 June 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Justification for type of information:
See IUCLID section 13 for category and read across justification

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Batch number: Not reported
- Expiry date: Not reported

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Oxon, UK.
- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age.
- Weight at study initiation: The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).
- Fasting period before study: Overnight fast immediately before dosing
- Housing: The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): 2014 Teklad Global Rodent diet (supplied by Harlan UK Limited, Oxon, UK) was allowed ad libitum throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water
- Acclimation period: Acclimatisation period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was 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.

IN-LIFE DATES: From: Day 1 To: Day 14

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: For the purpose of the study the test material was freshly prepared, as required, as a suspension in distilled water to give a dose level of 300 or 2000mg/kg bodyweight.
- Amount of vehicle (if gavage): Not stated
- Justification for choice of vehicle: Distilled water was the preferred vehicle of the test method.
- Lot/batch no. (if required): Not stated
- Purity: Not stated

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): Not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
Doses:
Following a sighting test at a dose levels of 300 and 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of test material, as a suspension in distilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.
No. of animals per sex per dose:
1 female at 300 mg/kg bw
1 female at 2000 mg/kg bw
4 females at 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight.

Results and discussion

Preliminary study:
A sighting test at a dose levels of 300 and 2000 mg/kg bw was performed.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
Signs of systemic toxicity noted were hunched posture, pilo-erection, ataxia, noisy respiration, sneezing and increased salivation. Animals appeared normal 2, 5 or 10 days after dosing.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Individual bodyweights and bodyweight changes are given in Table 5 (in any other information section)
Gross pathology:
No abnormalities were noted at necropsy.
Individual necropsy findings are given in Table 6 (in any other information section)

Any other information on results incl. tables

Table1              Individual Clinical Observations and Mortality Data -300mg/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

0=     No signs of systemic toxicity

Table 2              Individual Bodyweights and Bodyweight Changes -300mg/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

180

202

212

22

10

Table 3              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

Table 4              Individual Clinical Observations and Mortality Data -2000mg/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

H

H

HPA

HPA

HPA

HA

HA

H

0

0

0

0

0

0

0

0

0

0

3-0

Female

HRnS

HRnS

HPRn

HPRn

HARn

Rn

Rn

RnRs

RnRs

RnRs

RnRs

RnRs

RnRs

0

0

0

0

0

3-1

Female

H

HPA

HPA

HP

H

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2

Female

H

HPA

HPA

HA

H

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3

Female

H

HA

HA

HA

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0=     No signs of systemic toxicity

H =      Hunched posture

P =      Pilo-erection

A =      Ataxia

Rn =   Noisy respiration

Rs =   Sneezing

S =     Increased salivation

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

Dose Level

mg/kg

Animal Number
and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

2-0 Female

176

180

193

4

13

3-0 Female

176

178

189

2

11

3-1 Female

165

184

190

19

6

3-2 Female

186

198

213

12

15

3-3 Female

172

182

202

10

20

Table 6              Individual Necropsy Findings-2000mg/kg

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

2-0 Female

Killed Day 14

No abnormalities detected

3-0 Female

Killed Day 14

No abnormalities detected

3-1 Female

Killed Day 14

No abnormalities detected

3-2 Female

Killed Day 14

No abnormalities detected

3-3 Female

Killed Day 14

No abnormalities detected


Applicant's summary and conclusion

Interpretation of results:
other: Not classified (EU CLP (EC) No 1272/2008) and Category 5 (UN GHS version 7, 2017)
Remarks:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.
Executive summary:

Introduction. 

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

- OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (adopted 17 December 2001)

- Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Method. 

Following a sighting test at dose levels of 300 mg/kg bw and 2000 mg/kg bw, a further group of four fasted females was given a single oral dose of test material, as a suspension in distilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations.

Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg bw were hunched posture, pilo-erection, ataxia, noisy respiration, sneezing and increased salivation. There were no signs of systemic toxicity noted in the animal treated at a dose level of 300 mg/kg bw.

Bodyweight. 

All animals showed expected gains in bodyweight.

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.