N,N'-bis(5,5-dimethyl-1,3,2-dioxaphosphinane-2-oxide-2-yl)ethane-1,2-diamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 February 2014 to 14 February 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

See "Any other information" for details

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-({2-[(5,5-dimethyl-2-oxo-1,3,2λ⁵-dioxaphosphinan-2-yl)amino]ethyl}amino)-5,5-dimethyl-1,3,2λ⁵-dioxaphosphinan-2-one

EC Number:

835-272-7

Cas Number:

256374-76-2

Molecular formula:

C12H26N2O6P2

IUPAC Name:

2-({2-[(5,5-dimethyl-2-oxo-1,3,2λ⁵-dioxaphosphinan-2-yl)amino]ethyl}amino)-5,5-dimethyl-1,3,2λ⁵-dioxaphosphinan-2-one

Test material form:

solid: particulate/powder

Details on test material:

Name
Name: Reaction products of ethane-1,2-diamine, phosphoryl=trichloride and 2,2-dimethylpropane-1,3-diol which makes N,N'-bis(5,5-dimethyl-1,3,2-dioxaphosphinane=2-oxide-2-yl)ethane-1,2-diamine as a main component
Other name: SH-0850
CAS number: 256374-76-2 (main component)

Structural formula
Molecular formula: C12H26N2O6P2 (main component)
Molecular weight: 356.29 (main component)

Provided sample
Purity of the test substance: 100%
Lot number: SK-241002

Physical-chemical properties
Solubility in water: Less than 0.03% (w/w) by visual observation
Melting point: 277 °C
Appearance at normal temperatures: White powder

Storage condition
The test substance was stored in a dark place at room temperature.

Precaution for handling
Protective gloves, mask, glasses and clothes were put on in order to avoid contacts with skin or eyes and inhalation.

Specific details on test material used for the study:

No further details specified in the study report.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species and strain: New Zealand White rabbits
Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, HUNGARY
Justification of strain: The New Zealand White albino rabbit is one of the standard strains used for acute irritation toxicity studies.
Animal health: Only animals in acceptable health condition were used for the test.
Number of animals: 3
Age of animals at treatment: 11 weeks old
Sex: Male
Body weight range at the
beginning of the life phase: 2720-2865 g
at the end of the life phase: 2761-2892 g
Date of receipt: 05 February 2014
Acclimation time: 6 days
Animal identification: The animals were identified by engraved ear tags. The cages were marked with individual identity cards with information about study code, sex, cage number, dose group and individual animal number.

Husbandry
Number of animal room: 620
Lighting periods: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature range during the study: 20 ± 3 °C
Relative humidity during the study: 24- 48%
Housing/Enrichment: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
Ventilation: 15-20 air exchanges/hour
The temperature and relative humidity values were measured continuously. The measured range was checked at least daily during the acclimatisation and experimental phases.

Food and Feeding
Animals received UNI diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum. Animals were provided with the following batches:
 0381 12 13, expiry date: 14 February 2014
 0391 12 13, expiry date: 19 March 2014
The details of the diets used will be archived with the raw data and are not reported.

Water Supply
The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.

Water Analysis
The drinking water is routinely analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. The quality control analysis is performed once every three months and microbiological assessment is performed monthly by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A.u.36., Hungary). Copies of the relevant Certificates of Analysis are retained in the archives at CiToxLAB Hungary Ltd.

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Single dose of 0.5 g of SH-0850, applied to the test area.

Duration of treatment / exposure:

Duration of exposure: 4 hours.

Observation period:

72 hours after patch removal.

Number of animals:

3 animsl

Details on study design:

Dosage
The test item was used as supplied, as a single dose of 0.5 g of SH-0850, applied to the test area. The untreated skin of each animal served as a control.

Application of the Test Item
Patch testing was used to detect primary irritating effects of the test item. Three male animals in acceptable health condition were selected for this test.
Approximately 24 hours prior to the test, the hair was clipped from the back and flanks of the animals. Removal of hair was performed in two steps. The majority of hair was clipped with an electronic hair clipper and the remaining hair was moistened with water and shaved with a razor.
The test item was applied to an approximately 6 cm² area of intact skin as follows:
• A single layer of a fine medical gauze (open-weave with large holes) of approximately 5x5 cm was placed over the application area,
• The appropriate amount of test item was carefully spread over the application area (the gauze helped maintain the test item in place),
• Three more layers of gauze were placed over the test item,
• These gauze patches were kept in contact with the skin by a patch of clear plastic with a surrounding adhesive hypoallergenic plaster to ensure continued good contact between the moistened test item and the shaved skin.
• The entire trunks of the animals were wrapped with plastic wrap for 4 hours.
• Medical elastic tubing was placed over the plastic to keep it in place.
An initial test was performed using one animal. One hour after application of the test item, the application site was examined. No severe irritation or corrosive effect was found in the initial test, therefore the bandage was replaced and the exposure continued for a further 3 hours (a total 4 hours exposure). Two additional animals were then included in the study.

Duration of Exposure
Duration of exposure: 4 hours. After the treatment period, the test item was removed with water at body temperature.

OBSERVATIONS AND SCORING
Clinical Observations
Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes and then at 24, 48 and 72 hours after patch removal.

Scoring and Assessment of Local Reactions
The dermal irritation scores were evaluated according to the scoring system by Draize (1959). The animals were observed for 72 hours and the duration of the study was sufficient to evaluate fully the reversibility or irreversibility of the effects observed.

Measurement of Body Weight
Body weights were recorded at the beginning and at the end of experiment.

Termination
At the end of the observation period, euthanasia of the animal was by intramuscular injections of CP-Ketamin 10 % and CP-Xylazin 2 % followed by i.v. RELEASE 300 mg/ml inj. A.U.V. anaesthesia (see details in 3.1.2.). Death was verified by checking pupil and cornea reflex, absence of respiration and pulse.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

At observation one, 24, 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals.
As no clinical signs were observed the study was terminated after the 72 hours observation.
The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0.00, 0.00 and 0.00 respectively.

Other effects:

MORTALITY
There was no mortality observed during the study.

BODY WEIGHTS
There was no effect of treatment on body weight.

CLINICAL OBSERVATION
General Daily Examination
There were no treatment-related clinical signs noted.

Any other information on results incl. tables

SCORING OF ERYTHEMA FORMATION

Animal No./Sex	Body weight (g)		1 h	24 h	48 h	72 h
	At the beginning of the experiment	At the end of the experiment
00722/M	2720	2761	0	0	0	0
00723/M	2764	2789	0	0	0	0
00713/M	2865	2892	0	0	0	0
TOTAL	-	-	0	0	0	0

 

SCORING OF OEDEMA FORMATION

Animal No./Sex	Body weight (g)		1 h	24 h	48 h	72 h
	At the beginning of the experiment	At the end of the experiment
00722/M	2720	2761	0	0	0	0
00723/M	2764	2789	0	0	0	0
00713/M	2865	2892	0	0	0	0
TOTAL	-	-	0	0	0	0

 

M = male

h = hour

 

MEAN VALUES OF SKIN IRRITATION SCORES

(24, 48, 72 hours reading)

Animal Number	Sex	Erythema	Oedema
00722	Male	0.00	0.00
00723	Male	0.00	0.00
00713	Male	0.00	0.00

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

According to Directive 2001/59/EC, SH-0850 does not require classification as a skin irritant.
According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, SH-0850 does not require classification as a skin irritant.
According to the classification system based on the scheme devised by Draize (1959), SH-0850 is a "non-irritant".

Executive summary:

An acute skin irritation study was performed with SH-0850 in New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test item was evaluated according to the Draize method (OECD No.: 404, 2002).

 

A weight of 0.5 g for solid test item was applied to the skin of the experimental animals. The test item was applied as a single dose. Sufficient water to damp the material was used to ensure good contact with the skin and an adhesive clear plastic patch was applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control.

 

After 4 hours, the remaining test item was removed with water at body temperature.

 

To assess skin irritation, animals were examined at 1, 24, 48 and 72 hours after the patch removal. Additional general examinations were performed daily.

 

There was no mortality or systemic clinical changes related to SH-0850 administration.

 

There was no effect of treatment on body weight.

 

At observation one, 24, 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals.

 

As no clinical signs were observed the study was terminated after the 72 hours observation.

 

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0.00, 0.00 and 0.00 respectively.

 

According to Directive 2001/59/EC, SH-0850 does not require classification as a skin irritant.

 

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, SH-0850 does not require classification as a skin irritant.

 

According to the classification system based on the scheme devised by Draize (1959), SH-0850 is a "non-irritant".