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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2015-08-25 to 2015-09-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes (incl. QA statement)
Remarks:
2013-05-06
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Phosphonium, tetrakis(hydroxymethyl)-, sulphate (2:1) (salt), polymer with urea.
EC Number:
613-239-6
Cas Number:
63502-25-0
Molecular formula:
Not applicable
IUPAC Name:
Phosphonium, tetrakis(hydroxymethyl)-, sulphate (2:1) (salt), polymer with urea.
Test material form:
other: Liquid
Details on test material:
THPS-Urea Co-polymer

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11 weeks old)
- Weight at study initiation: 172 -214 g
- Fasting period before study: yes
- Housing: 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 25 August 2015 To: 29 September 2015

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
only for 50 mg/kg group
Details on oral exposure:
VEHICLE
- Water: Elix, Millipore S.A.S., Molsheim, France
- Concentration in vehicle:
- Treatment volume:
2000 mg/kg: 2.1157 mL/kg bw.
300 mg/kg: 0.3174 mL/kg bw.
50 mg/kg: 0.5 mL/kg bw.
- Justification for choice of vehicle: the substance is soluble in water

DOSAGE PREPARATION: The preparations (w/w) were kept at room temperature and were dosed within 1 hour after adding the vehicle to the test substance. Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies.

CLASS METHOD:
- Rationale for the selection of the starting dose: Toxicity not expected at this dose level
Doses:
First experiment: 2000 mg/kg
Second experiment: 300 mg/kg
Third and fourth experiment: 50 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: day 1: 1h, 2h and 4h after dosing, and then twice daily
- Frequency of weighing: Days 1 (pre-administration), 8 and 15 and at death or necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic observations at death or necropsy
Statistics:
Not applicable

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 50 - < 300 mg/kg bw
Based on:
act. ingr.
Mortality:
2000 mg/kg bw: 3/3
300 mg/kg: 3/3
50 mg/kg: 0/6
Clinical signs:
other: At 2000 mg/kg, lethargy, hunched posture, abnormal gait, piloerection and/or ptosis were noted on Day 1. At 300 mg/kg, hunched posture and piloerection were noted on Day 1. At 50 mg/kg, hunched posture and/or piloerection were noted on Day 1.
Gross pathology:
At 2000 and 300 mg/kg, abnormalities of the stomach (irregular surface, hardened and/or watery clear contents (only 300 mg/kg)) were found at macroscopic post-mortem examination.
At 50 mg/kg, no abnormalities were found at macroscopic examination.
(Beginning of autolysis was noted for the animals treated at 50 mg/kg. This was considered not toxicologically relevant).

Any other information on results incl. tables

Body Weights


SEX/DOSE LEVEL


ANIMAL


DAY 1

DAY 2*
body weigth

at death


DAY 8


DAY 15

FEMALES 2000 MG/KG

1

189

181

---

---

2

185

183

---

---

3**

 

 

---

---

MEAN

193

 

 

 

ST.DEV.

11

 

 

 

N

3

 

 

 

FEMALES 300 MG/KG

4**

 

 

---

---

5

192

190

---

---

6

214

211

---

---

MEAN

188

 

 

 

ST.DEV.

28

 

 

 

N

3

 

 

 

FEMALES 50 MG/KG

7

194

na

203

210

8

197

na

212

217

9

177

na

180

189

MEAN

189

 

198

205

ST.DEV.

11

 

17

15

N

3

 

3

3

FEMALES 50 MG/KG

10

184

na

198

211

11

172

na

201

203

12

190

na

208

216

MEAN

182

 

202

210

ST.DEV.

9

 

5

7

N

3

 

3

3

 * Animals 1-6 were found dead on Day 2.

** There were uncertainties in the body weights of these animals (animal 3:205 and 181; animal 4: 158 and 206 gram). These body weights where therefore not used for interpretation. Sufficient data was available.

Na Not applicable

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Under the test conditions of this study, the oral LD50 value of Phosphonium, tetrakis (hydroxymethyl)-sulphate (2:1); polymer with urea in Wistar rats was established to be within the range of 50-300 mg/kg body weight (corresponding to the Active Ingredient).
Executive summary:

Assessment of acute oral toxicity with Phosphonium, tetrakis (hydroxymethyl)-sulphate (2:1); polymer with urea in the rat (Acute Toxic Class Method). The study was carried out based on the guidelines described in:

OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method". Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method". EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity" and JMAFF Guidelines (2000), including the most recent revisions.

 

Initially, Phosphonium, tetrakis (hydroxymethyl)-sulphate (2:1); polymer with urea was administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight. In a stepwise procedure three additional groups of three females were dosed at 300, 50 and 50 mg/kg body weight as active ingredient. The animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

 

All animals treated at 2000 and 300 mg/kg were found dead on Day 2.

 

At 2000 mg/kg, lethargy, hunched posture, abnormal gait, piloerection and/or ptosis were noted on Day 1.

At 300 mg/kg, hunched posture and piloerection were noted on Day 1.

At 50 mg/kg, hunched posture and/or piloerection were noted on Day 1.

 

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

 

At 2000 and 300 mg/kg, abnormalities of the stomach (irregular surface, hardened and/or watery clear contents (only 300 mg/kg)) were found at macroscopic post-mortem examination. At 50 mg/kg, no abnormalities were found at macroscopic examination.

 

Under the test conditions of this study, the oral LD50 value of Phosphonium, tetrakis (hydroxymethyl)-sulphate (2:1); polymer with urea in Wistar rats was established to be within the range of 50-300 mg/kg body weight (as active ingredient).

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