[No public or meaningful name is available]

Acute Toxicity: oral

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

Test material information

Constituent 1

Reference substance name:

Tetrakis(hydroxymethyl)phosphonium sulphate (2:1) and its oligomerisation products with urea

Molecular formula:

Not applicable

IUPAC Name:

Tetrakis(hydroxymethyl)phosphonium sulphate (2:1) and its oligomerisation products 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).