Tetraisopropyl methylenebisphosphonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

from 1989-12-27 to 1990-02-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No indication on the purity of the substance

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

To determine the irritation potential of the test article when applied dermally. This study was designed to comply with the FHSA standards set forth by 16 CFR 1500.41.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetraisopropyl methylenebisphosphonate

EC Number:

216-765-0

EC Name:

Tetraisopropyl methylenebisphosphonate

Cas Number:

1660-95-3

Molecular formula:

C13H30O6P2

IUPAC Name:

tetraisopropyl methylenebis(phosphonate)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: No data
- Weight at study initiation: 2.0 -2.5 kg
- Housing: The animals were housed 2/cage in suspended wire mesh cages. Bedding was placed beneath the cages and changed twice/week.
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow (Diet #5321)
- Water (e.g. ad libitum): yes
- Acclimation period: At lest one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Controled but no data available
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From 1990-01-02 to 1990-01-05

Test system

Type of coverage:

occlusive

Preparation of test site:

other: clipped, abraded on left side and intact on right side

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL /site

Duration of treatment / exposure:

24 hour oclusive exposure

Observation period:

72 hours

Number of animals:

6 (3 males and 3 females)

Details on study design:

TEST SITE
Prior to application of the test article, the back and sides of each animal were clipped free of hair. The left side of each animal was abraded with a bent tip needle. Three abrasions, approximately 2-3 cm apart, extending the length of the exposure site were made. The abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to produce bleeding. The right side of each animal remained intact.

EXPERIMENTAL DESIGN
The test article was used as received and dosed by volume, 0.5 ml/site, for a total dose of 1.0 ml/rabbit. The test article was applied to two areas, 1 intact and 1 abraded, on the prepared site, on the back of each of six rabbits.
The treated sites were covered with 2.5 cm square gauze patches which were secured with adhesive tape. The torso was wrapped with plastic which was secured with adhesive tape. The sites were occluded for 24 hours at which time the patches were removed.

TYPE AND FREQUENCY OF OBSERVATIONS
Animals were observed for skin reactions at 24 and 72 hours after application of the test article. Erythema and edema were scored according to the numerical Draize technique. Body weights were recorded pretest. Additional signs were described.
The general health of the animals was monitored at each observation time.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24h and 72h

Score:

1.17

Max. score:

1.17

Reversibility:

no data

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h and 72h

Score:

0.75

Max. score:

1.17

Reversibility:

no data

Remarks on result:

other: Intact skin

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h and 72h

Score:

0.835

Max. score:

1.17

Reversibility:

no data

Remarks on result:

other: Abraded skin

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24h and 72h

Score:

0.335

Max. score:

0.67

Reversibility:

no data

Remarks on result:

other: Intact skin

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24h and 72 h

Score:

0.42

Max. score:

0.67

Reversibility:

no data

Remarks on result:

other: Abraded skin

Any other information on results incl. tables

Individual scores

Animal number		C7859	C7860	C7861	C7808	C7813	C7814	Mean Scores
Pretest body weight (kg)		2.4	2.5	2.0	2.3	2.0	2.0
Erythema & eschar formation
Intact Skin	24h	1	1	1	2	1	1	1.17
	72h	0	0	0	1	0	1	0.33
Abraded skin	24h	1	1	1	2	1	1	1.17
	72h	1	0	0	1	0	1	0.50
Edema
Intact skin	24h	2	0	1	0	0	1	0.67
	72h	0	0	0	0	0	0	0
Abraded skin	24h	2	0	1	0	0	1	0.67
	72h	1	0	0	0	0	0	0.17
Sum of mean score								4.68
Primary dermal irritation index = sum of mean score /4								1.17

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The substance was not considered to be irritant.

Executive summary:

The dermal irritation of TIPMDP was tested on 6 New Zealand Albino rabbits in a primary dermal irritation following the standards set forth by FHSA, 16 CFR 1500.3(c)(4). 0.5 ml of the test substance was applied to 1 intact and 1 abraded site on the clipped back for a total dose of 1.0 ml/rabbit. The sites were occluded for 24 hours. The skin reactions were evaluated by the Draize technique at 24 and 72 hours after dosing. Body weights were recorded pretest. The Primary Irritation Index was calculated.

Erythema , slight to well defined at 24 hours, was absent to slight at 72 hours. Edema, absent to well defined at 24 hours, was absent at 72 hours. Abnormal systemic signs of diarrhea and few feces were noted during the observation periods. The substance was not found to be irritating to the skin.