Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 13 April 2010 and 05 May 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted to GLP and in compliance with agreed protocols, with no deviations from standard test guidelines (OECD 420, EU Method B1 bis) and no methodological deficiencies. This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).

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 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)
Remarks:
Date of inspection: 19-21 July 2011, Date of signature: 31 August 2011
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Sponsor's identification: Tetrairon tris(pyrophosphate)
CAS number: 10058-44-3
EC number: 233-190-0
Description: off white powder
Batch number: 2-47501-56
Purity: 97%
Date received: 12 April 2012
Expiry date: 28 February 2015
Storage conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 165-189 g. 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): ad libitum (2014C Teklad Global Rodent diet supplied by Harlan Teklad, Oxon, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

IN-LIFE DATES: From: 15 May 2012 To: 07 June 2012

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:
water
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
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 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
At the end of the observation period 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.


Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths in the 5 animals tested.
Clinical signs:
Individual clinical observations and mortality data are given in Table 1. No signs of systemic toxicity were noted.
Body weight:
Individual bodyweights and bodyweight changes are given in Table 2.
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
Individual necropsy findings are given in Table 3.
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1. Individual clinical observations and mortality data.

 

 

Dose level mg/kg

Animal

number

and sex

Effects noted after dosing (hours)

Effects noted during periods after doing

(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

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

 

 

 

Table 2. Individual bodyweight 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

2000

1-0

Female

165

193

206

28

13

2-0

Female

189

210

218

21

8

2-1

Female

177

197

208

20

11

2-2

Female

179

191

204

12

13

2-3

Female

177

201

215

24

14

 

 

 

Table 3. 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

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

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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 (Globally Harmonised Classification System: Unclassified).
This study is considered to be reliable and acceptable for use as a key study in accordance with Regulation (EC) No. 1907/2006 (REACH) and for the purposes of classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).