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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 01 May 2012 and 31 May 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
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)
Remarks:
No analysis was carried out to determine the homogeneity, concentration or stability of the test item formulation. This exception is considered not to affect the purpose or integrity of the study.
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
semi-solid (amorphous): gel
Remarks:
migrated information: paste
Details on test material:
Sponsor's identification: Bis(2,4-dichlorobenzoyl) peroxide (CAS# 133-14-2), paste, 50% in silicone oil
Description : white paste
Batch number : 1012011395
Purity : 50.7%
Date received : 08 November 2011
Expiry date : 01 January 2013
Storage conditions: approximately -20°C in the dark
The integrity of supplied data relating to the identity, purity and stability of the test item is the responsibility of the Sponsor.
A Certificate of Analysis supplied by the Sponsor is given in Appendix 2 (attachment 1)

Test animals

Species:
rat
Strain:
Sprague-Dawley
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 animals were nulliparous and non-pregnant. After an acclimatisation 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 bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group.
The animals were housed in groups of 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 analysed 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. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. 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.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 female @2000 mg/kg
3 female @2000 mg/kg
Control animals:
no
Details on study design:
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 (Female)
2000 200 10 3
2000 200 10 3
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 bodyweight 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.
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.
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
At the end of the observation period the 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.

Results and discussion

Effect levels
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.
There were no deaths.
Clinical signs:
Individual clinical observations are given in Table 1.
No signs of systemic toxicity were noted.
Body weight:
Individual bodyweights and weekly bodyweight changes are given in Table 2.
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
Individual necropsy findings are given in Table 3.
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Evaluation of Data

Data evaluations included the relationship, if any, between the exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

The results were also evaluated according to the Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.

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

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

2-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

0

0

0

0

0

0

0

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

0= No signs of systemic toxicity

Table 2              Individual Bodyweights and Weekly Bodyweight Changes

Dose Level

mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

1-0 Female

164

185

189

21

4

1-1 Female

161

186

211

25

25

1-2 Female

161

185

202

24

17

2-0 Female

165

178

187

13

9

2-1 Female

170

191

199

21

8

2-2 Female

177

196

216

19

20

Table3              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

Killed Day 14

No abnormalities detected

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

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2500 mg/kg bodyweight (Globally Harmonised 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, Labelling and Packaging of Dangerous Substances.
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 Commission regulation (EC) No. 440/2008

Method. A group of three fasted females was treated with the test item at a dose level of2000 mg/kg bodyweight. This was followed by a further group of three fasted females at the same dose level.

The test item was administered orally as asuspensioninarachis oil BP. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Bodyweight. All animals showed expected gains in bodyweight over the study period.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2500 mg/kg bodyweight (Globally Harmonised 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, Labelling and Packaging of Dangerous Substances.