Diethyl (hydroxymethyl)phosphonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and appropriate guidelines

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

n/a

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Diethyl (hydroxymethyl)phosphonate

EC Number:

221-391-6

EC Name:

Diethyl (hydroxymethyl)phosphonate

Cas Number:

3084-40-0

Molecular formula:

C5H13O4P

IUPAC Name:

diethyl (hydroxymethyl)phosphonate

Constituent 2

Reference substance name:

Diethoxyphosphoryl methanol

IUPAC Name:

Diethoxyphosphoryl methanol

Test material form:

liquid

Details on test material:

Clear transparent liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Source: Harlan Italy s.r.l.
Rabbit, New Zealand White Specific Pathogen Free (SPF)
Number of animals and sex - 3 female rabbits (nulliparous and non-pregnant)
Age at order - 29 to 35 weeks old.
Weight range at arrival- 2.86 to 3.78 kg
Husbandary: The rabbits were housed individually in plastic cages with perforated floors.
Light: 12 hr artificial light 12 hr dark.
Animal room environmental controls were set to maintain temperature within the range 16 to 20°C, and relative humidity within 40 to 70%.
Accommodation: Individually in labelled cages
Acclimatisation period was at least 5 days before start of the treatment
Diet- STANRAB (P) SQC, Special Diets Services, Witham, Essex CM8 3AD, UK ad libitum thorought the day.
Water- Drinking water was supplied to each cage via a water bottle ad libitum.

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL of the test substance

Duration of treatment / exposure:

4h

Observation period:

Examination of the treated skin was made on removal of the dressings (for 3 minute or
one hour exposures) and approximately 1, 24, 48 and 72 hours later.

Number of animals:

3 animals

Details on study design:

As the irritancy of the substance was unknown, a single animal was dosed to address potential irritation of the test item. As the response to treatment was considered to be within acceptable limits, a futher 2 animals were dosed, bringing the animal's group size to 3. On the day before dosing a suitable test site was clipped free of hair on both sides of the mid-line of the dorsal surfaces of the trunk of each animal. The test item was used in the form suplied (liquid). A quantity of 0.5ml of the test material was spread evenly over a 2.5cmx 2.5cm cotton gauze pad and placed onto the animal's skin with the test item in direct contact with the skin. A strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage. At the end of the exposure period the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with lukewarm water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper. Mortality and morbidity were observed twice daily. Bodyweight was taken on Day 1 and on termination (Day 4). Examination of the treated skin was made on removal of the dressings (for 3 minute or one hour exposures) and approximately1, 24, 48 and 72 hours after the end of the 4 hour exposure period. Following completion of the observation period the animals were humanely killed by an
intravenous injection of sodium pentobarbital.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Reversibility:

no data

Remarks on result:

other: No signs of dermal irritation were observed.Thus, no need to present data on reversibility.

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Reversibility:

no data

Remarks on result:

other: No signs of dermal irritation were observed.Thus, no need to present data on reversibility.

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Reversibility:

no data

Remarks on result:

other: No signs of dermal irritation were observed.Thus, no need to present data on reversibility.

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Reversibility:

no data

Remarks on result:

other: No signs of dermal irritation were observed.Thus, no need to present data on reversibility.

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Reversibility:

no data

Remarks on result:

other: No signs of dermal irritation were observed.Thus, no need to present data on reversibility.

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Reversibility:

no data

Remarks on result:

other: No signs of dermal irritation were observed.Thus, no need to present data on reversibility.

Irritant / corrosive response data:

Corrosion: There was no evidence of a corrosive effect on the skin
Colouration: No staining of the treated skin by the test substance was observed
Toxicity/Mortality: There was no indication of a systemic toxicity effect in the animals during the test period and no mortality occurred.
Changes in body weight during the course of the study were not remarkable.

Other effects:

Very slight erythema was evident at the test site of one animal one hour after bandage removal; no other dermal reaction was observed in any animal throughout the duration of the study.

Any other information on results incl. tables

No further information

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Not classified Criteria used for interpretation of results: EU

Conclusions:

The Primary Irritation Index was calculated to be 0.0; E06-16 was classified as ‘non-irritant’
according to the criteria of the ECETOC and did not require labelling in accordance with
Commission Regulation 1272/2008.

Executive summary:

n/a