Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2017-07-11 to 2017-10-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
2015-09-22
Test type:
fixed dose procedure
Limit test:
yes

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:
liquid
Details on test material:
Chemical name: Tetrakis[hydroxymethyl]phosphonium sulphate-urea copolymer

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany.
- Females (if applicable)female rats were nulliparous and non-pregnant
- Age at study initiation: Young adult rats
- Weight at study initiation: Between 220 g and 245 g
- Fasting period before study:
- Housing: Individual caging Type II. polypropylene/polycarbonate
- Bedding and nesting:“Lignocel 3/4-S Hygienic Animal Bedding” and “Arbocel crinklets natural” nest building material produced by J. Rettenmaier & Söhne GmbH + Co.KG (D-73494 Rosenberg, Germany) was available to animals during the study.
- Enrichment: Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet (e.g. ad libitum): Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany (batch number: 262 21592, expiry date: 31 January 2018)
- Water (e.g. ad libitum): tap water from the municipal supply, as for human consumption from a 500 mL bottle, ad libitum.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 28.1 °C (Due to technical reasons, temperature values (maximum of 28.1 °C) outside the expected range of 22 ± 3 °C were recorded during the study. However, these differences of the environmental parameter were considered not to adversely affect the results of or integrity of the study as confirmed by the clinical Veterinarian.)
- Humidity (%): 32 – 70 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 2017-07-20 to 2017-08-08

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: approximately 10% area of the total body surface
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the area of skin treated with the test item was washed with water of body temperature.
- Time after start of exposure: 24h

TEST MATERIAL
- The active ingredient content of the test item is 68.8% (w/w), therefore a correction factor of 1.45 was used to calculate the 2000 mg/kg bw dose level.
Duration of exposure:
24h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 1h, 5h and dailly for 14 days after treatment (Clinical signs). Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.
- Weighing: Days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic examination was performed on all animals. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
Tetrakis[hydroxymethyl]phosphonium sulphate-urea copolymer did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical signs:
other: There were no systemic clinical signs noted in any animal throughout the study.
Gross pathology:
At necropsy, a few crusts were seen on the skin at the dorsal thoracic area in one female animal. Besides this, there was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw
Other findings:
None

Any other information on results incl. tables

Clinical observations (2000 mg/kg)

Animal N°

Obervations

Observation days

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

M 229

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

M 230

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

M 231

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

M 232

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

M 233

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

F 234

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

F235

Symptom free

+

+

-

-

-

-

-

-

-

-

-

-

-

-

-

-

2/16

Crust – treated area

-

-

-

+

+

+

+

+

+

+

+

+

+

+

+

+

13/16

Erythema

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

3/16

F 236

Symptom free

+

+

-

-

-

-

-

-

-

+

+

+

+

+

+

+

9/16

Crust – treated area

-

-

-

+

+

+

+

+

+

-

-

-

-

-

-

-

6/16

Erythema

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

3/16

F 237

Symptom free

+

+

-

-

-

-

+

+

+

+

+

+

+

+

+

+

12/16

Crust – treated area

-

-

-

+

+

+

-

-

-

-

-

-

-

-

-

-

3/16

Erythema

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

2/16

F 238

Symptom free

+

+

-

+

+

+

+

+

+

+

+

+

+

+

+

+

15/16

Erythema

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

1/16

+ = present         h = hour(s)          Treatment day = Day 0                 

- = Absent

Frequency of observation = number of occurrence of observation / total number of observations

Erythema severity: 1 = very slight, 2 = well defined; 3 = Modderate to severe; 4 = severe to slight eschar formation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute dermal median lethal dose (LD50 value) of the test item Tetrakis[hydroxymethyl]phosphonium sulphate-urea copolymer was found to be above 2000 mg/kg bw in male and female Crl:WI rats. There were no systemic effects of treatment.

According to the GHS criteria, Tetrakis[hydroxymethyl]phosphonium sulphate-urea copolymer can be ranked as Unclassified for acute dermal exposure.
Executive summary:

An acute dermal toxicity study was performed with test item Tetrakis[hydroxymethyl]phosphonium sulphate-urea copolymer in Crl:WI rats, in compliance with OECD Guideline No. 402.

A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as a single dermal 24-hour exposure followed by a 14-day observation period.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).

 

RESULTS

Mortality

Tetrakis[hydroxymethyl]phosphonium sulphate-urea copolymer did not cause mortality at the dose level of 2000 mg/kg bw.

Clinical Observations

There were no systemic clinical signs noted in any animal throughout the study.

Local dermal signs

Very slight erythema in four females (Days 1-3) and crust in three females were seen at the treated area after treatment with the test item. Besides these, no local dermal signs were observed during the 14 days observation period.

Body weight and body weight gain

Body weight gains of Tetrakis[hydroxymethyl]phosphonium sulphate-urea copolymer treated animals during the study showed no indication of a test item-related effect.

Macroscopic Findings

At necropsy, a few crusts were seen on the skin at the dorsal thoracic area in one female animal. Besides this, there was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

 

CONCLUSIONS

Under the conditions of this study, the acute dermal median lethal dose (LD50 value) of the test item Tetrakis[hydroxymethyl]phosphonium sulphate-urea copolymer was found to be above 2000 mg/kg bw in male and female Crl:WI rats. There were no systemic effects of treatment.

According to the GHS criteria, Tetrakis[hydroxymethyl]phosphonium sulphate-urea copolymer can be ranked as Unclassified for acute dermal exposure.