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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 October 2006 and 13 November 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection: August 2005: Date of certificate: November 2005
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
482-130-1
EC Name:
-
Cas Number:
848301-87-1
Molecular formula:
Main general molecular formula: CnH(2n+2)
IUPAC Name:
Paraffin waxes (Fischer-Tropsch), full range, C15-50 - branched and linear
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Paraffin waxes (Fischer-Tropsch), full range, C15-50 - branched and linear
- Physical state: Turbid liquid
- Lot/batch No.: Not reported
- Storage condition of test material: Room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, 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 bodyweights fell within an interval of ± 20% of the initial bodyweight of the first treated animal.
- 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 up to four in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): free access to mains drinking water and food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, 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.
- Water (e.g. ad libitum):free access to mains drinking water and food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, 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.
- Acclimation period: 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.

ENVIRONMENTAL CONDITIONS
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.

IN-LIFE DATES: From: Day 0 To: Day 14

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE :
- Concentration in vehicle: Not applicable
- Amount of vehicle (if gavage):Not applicable
- Justification for choice of vehicle:Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable

MAXIMUM DOSE VOLUME APPLIED: 6.18 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:Following a preliminary test in which there was no death at a dose level of 5000 mg/kg, an additional four fasted female animals were given a single oral dose of undiluted test material at a dose level of 5000 mg/kg bodyweight.
Doses:
At the request of the Sponsor 5000 mg/kg was chosen as the starting dose to comply with other non-EU Regulations.
A total of five animals were therefore treated at a dose level of 5000 mg/kg in the study.
No. of animals per sex per dose:
5 females at 5000 mg/kg
Control animals:
not specified
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 subsequently once 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,organ weights, histopathology, other: 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 Data

Results and discussion

Preliminary study:
No signs of systemic toxicity noted (single animal at 5000 mg/kg).
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: No 95% CL stated
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted.
Body weight:
Individual bodyweights and bodyweight changes are given in the table below.
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

Any other information on results incl. tables

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

5000

1-0

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

2-3

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 


Individual Bodyweights and Bodyweight Changes

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

5000

1-0 Female

228

256

273

28

17

2-0 Female

225

253

289

28

36

2-1 Female

218

240

280

22

40

2-2 Female

223

259

289

36

30

2-3 Female

215

249

262

34

13

 


Individual Necropsy Findings

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

5000

1-0 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

2-3 Female

Killed Day 14

No abnormalities detected


0= No signs of systemic toxicity

Applicant's summary and conclusion

Interpretation of results:
other: EU-GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Sprague Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight.
Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material in the Sprague‑Dawley CD 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)

§        Method B.1 bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC

Method. Following a preliminary test in which there was no death at a dose level of 5000 mg/kg, an additional four fasted female animals were given a single oral dose of undiluted test material at a dose level of 5000 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. There were no signs of systemic toxicity.

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 Sprague‑Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight (Globally Harmonised Classification System-Unclassified).