Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 17th January to 14th February 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study in compliance wih the GLP but no certificate of analysis was available.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: pale yellowish/middle-viscous liquid
Details on test material:
- Name of test material (as cited in study report): POLYFIX N SAUER, Isobutyl phosphorsäureester
- Synonymous: Reaction Mass of "Diisobutyl hydrogen phosphate and Isobutyl dihydrogen", IBAP

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deuchland GmbH, D97633 Sulzfeld, Germany
- Age at study initiation: no data
- Weight at study initiation: 172 g - 181 g
- Fasting period before study: overnight
- Housing: 2 or 3 per cage
- Bedding: pinewood sawdust "lignocel Faserm" from Altromin, D-32791 Lage, Lippe
- Diet: "Altromin 1314" from Altromin GmbH, D-32791 Lage, Lippe ad libitum
- Water: Domestic water acidified with hydrochloroc acid to pH 2.5 ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): at least 30% preferably not exceed 70%
- Air changes (per hr): 10 times
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: January 17, 2007 To: February 14, 2007

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: no data


MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on the result of the sighting study, in which one female rat was given the test substance in a 2000 mg/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
4 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: each rat was observed 30 min, 2, 4 and 6 hours after administration and thereafter daily. Body weight was recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and gross necrospsy examination.


Statistics:
Not required

Results and discussion

Preliminary study:
The animal included in the sighting study survived the treatment and showed clinical signs of toxicity. These consisted of dyspnoea and piloerection 30 minutes and 2 hours after the administration of the test item. After 4 and 6 hours piloerection was still observed. From day 1 to the end on the observation period on day 14 no abnormalities were revealed.
Body weight gain was normal during the study period (see Table 1).
The post mortem inspection revealed no pathological abnormalities.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality during the main study
Clinical signs:
Most of the animals showed signs of toxicity ranging from slight to severe.
Animals N°2, N°4 and N°5 showed dyspnea and piloerection 30 minutes and 2 hours after the application of the test item, whereas hunched posture and piloerection were observed at animal N°3. After 4 and 6 hours, animal N°2 still showed dyspnea and piloerection. Hunched posture and piloerection were observed at animal N°2, N°3 and N°5 during this observation phase. On day 1, only animal N°2 still showed piloerection. No abnormalities were revealed at animal N°3, N°4 and N°5. From day 2 to the end of the observation period on day 14 all four animals showed normal behaviour.
Body weight:
The rats showed normal body weight gain during the study period
Gross pathology:
The gross necropsy of the animals revealed no pathological abnormalities
Other findings:
no other findings

Any other information on results incl. tables

Table 1 : Body Weight

Sighting study

Individual values (g)  

Animal N°

Dose

mg/kg BW

Sex

Day 0

Day 7

Day 14

1

2000

Female

152

186

205

  

Main study

 Mean values (g)

Dose

mg/kg BW

Sex

Day 0

Day 7

Day 14

Mean

SD

n

Mean

SD

n

Mean

SD

n

2000

Female

175

4

4

195

5

4

220

2

4

SD: Standard deviation

N: Number of animals

 Individual values (g)

Animal N°

Dose

mg/kg BW

Sex

Day 0

Day 7

Day 14

2

2000

Female

172

198

218

3

2000

Female

174

191

223

4

2000

Female

181

200

220

5

2000

Female

172

189

218

  

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions of this study, the acute median lethal dose (LD50) of the Reaction mass of "Diisobutyl hydrogen phosphate and Isobutyl dihydrogen phosphate" was higher than 2000 mg/kg bw. Based on this result, no classification is required according to EU criteria.
Executive summary:

The acute oral toxicity of the Reaction mass of "Diisobutyl hydrogen phosphate and Isobutyl dihydrogen phosphate" was assessed in a study according to the Fixed Dose Procedure (OECD Guideline 420; EC test method B1.bis) and in accordance with GLP. Following a range-finding study in one female Wistar rat at 2000 mg/kg bw, four further fasted female rats were given a single oral dose of test material, as a suspension in water at the same dose level. The animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination.

There were no deaths during the study. On the day of dosing, all animals showed piloerection with dyspnea and/or hunched posture. Piloerection persisted to the following day in one animal only. All animals showed normal behaviour from day 2 of observation. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy.

Under these experimental conditions, the LD50 was determined to be higher than 2000 mg/kg bw for the acute oral toxicity of the Reaction mass of "Diisobutyl hydrogen phosphate and Isobutyl dihydrogen phosphate". Therefore no classification is required according to the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC criteria.

 

This acute oral study is classified as acceptable. It satisfies the guideline requirement for an acute oral study in the rats.