Tetraisopropyl methylenebisphosphonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1993-03-08 to 1993-09-15

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study was designed to comply with the standards set forth by FHSA 16 CFR 1500.42.

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 material form:

other: liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: No data
- Weight at study initiation: 2.7 -3.2 kg
- Housing: The animals were housed 1/cage in suspended cages. Bedding was placed beneath the cages and changed at least three times/week.
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow (Diet #5321)
- Water: ad libitum
- Acclimation period: At least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Controlled but no data oe the values
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From 1993-08-10 to 1993-08-24

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The contralateral eye served as a control.

Amount / concentration applied:

0.1 ml of the test article was placed by syringe or syringe-type applicator into the conjunctival sac which was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together briefly to insure adequate distribution of the test article. One eye of each rabbit was dosed. The contralateral eye served as a control.

Duration of treatment / exposure:

Once

Observation period (in vivo):

The treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva on days 1, 2, 3, 7 and 14. Ocular reactions were graded according to the numerical Draize technique. Additional signs were described. Body weights were recorded pretest.
The general health of the animals was monitored at each observation time.

Number of animals or in vitro replicates:

6 females

Details on study design:

The primary eye irritation score for each rabbit was calculated from the weighted Draize scale. The method of calculation is indicated on the attached scale.
The irritation potential was determined by counting the number of rabbits with positive irritation on days 1, 2 or 3. Positive irritation is defined as any score for opacity or iritis, or 2 or more for redness or chemosis. The test article is an irritant if 4 or more rabbits had a positive score at any time period.

Results and discussion

In vitro

Results

Remarks on result:

not measured/tested

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.97

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.83

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Other effects:

There were no abnormal physical signs noted during the observation period.

Any other information on results incl. tables

 

N° animal	Sex	Item	Tissue	Reading	Day 1	Day 2	Day 3	Day 7	Day 14
C7359	Female	A	Cornea	Opacity	0h	2	2	0	0
		B		Area	0	1	1	0	0
		1°) Total (A x B) X5			0	10	10	0	0
		C	Iris		1	1	0	0	0
		2°) Total C x 5			5	5	0	0	0
		D	Conjunctiva	Redness	2	2	1	1	0
		E		Chemosis	2	2	2	1	0
		F		Discharge	2	2	0	0	0
		3°) (D+E+F) x2			12	12	6	4	0
		Totals = 1 + 2 + 3			17	27	16	4	0
		systemic observations			A	A	A	A	A
		Pretest body weight= 2.7 kg
N° animal	Sex	Item	Tissue	Reading	Day 1	Day 2	Day 3	Day 7	Day 14
C7360	Female	A	Cornea	Opacity	0h	2	3	2	0
		B		Area	0	2	1	1	0
		1°) Total (A x B) X5			0	20	15	10	0
		C	Iris		1	1	1	0	0
		2°) Total C x 5			5	5	5	0	0
		D	Conjunctiva	Redness	3	3	2	2	0
		E		Chemosis	3	3	2	2	0
		F		Discharge	2	2	2	1	0
		3°) (D+E+F) x2			16	16	12	10	0
		Totals = 1 + 2 + 3			21	41	32	20	0
		systemic observations			A	A	A	A	A
		Pretest body weight= 3.2 kg
N° animal	Sex	Item	Tissue	Reading	Day 1	Day 2	Day 3	Day 7	Day 14
C7361	Female	A	Cornea	Opacity	2	2	2	0	0
		B		Area	1	1	1	0	0
		1°) Total (A x B) X5			10	10	10	0	0
		C	Iris		1	1	1	0	0
		2°) Total C x 5			5	5	5	0	0
		D	Conjunctiva	Redness	2	2	2	1	0
		E		Chemosis	2	2	2	0	0
		F		Discharge	2	2	2	0	0
		3°) (D+E+F) x2			12	12	12	2	0
		Totals = 1 + 2 + 3			27	27	27	2	0
		systemic observations			A	A	A	A	A
		Pretest body weight= 3.1 kg
N° animal	Sex	Item	Tissue	Reading	Day 1	Day 2	Day 3	Day 7	Day 14
C7362	Female	A	Cornea	Opacity	0h	2	2	3p	0hp
		B		Area	0	1	2	3	0
		1°) Total (A x B) X5			0	10	20	45	0
		C	Iris		0	1	1	1	0
		2°) Total C x 5			0	5	5	5	0
		D	Conjunctiva	Redness	2	2	2	2	1
		E		Chemosis	2	2	2	2	2
		F		Discharge	2	2	2	2	2
		3°) (D+E+F) x2			12	12	12	12	10
		Totals = 1 + 2 + 3			12	27	37	62	10
		systemic observations			A	A	A	A	A
		Pretest body weight= 2.9 kg
N° animal	Sex	Item	Tissue	Reading	Day 1	Day 2	Day 3	Day 7	Day 14
C7363	Female	A	Cornea	Opacity	0	2	2	0	0
		B		Area	0	1	1	0	0
		1°) Total (A x B) X5			0	10	10	0	0
		C	Iris		1	1	1	0	0
		2°) Total C x 5			5	5	5	0	0
		D	Conjunctiva	Redness	2	2	2	0	0
		E		Chemosis	2	2	2	0	0
		F		Discharge	2	2	2	0	0
		3°) (D+E+F) x2			12	12	12	0	0
		Totals = 1 + 2 + 3			17	27	27	0	0
		systemic observations			A	A	A	A	A
		Pretest body weight= 2.9 kg
N° animal	Sex	Item	Tissue	Reading	Day 1	Day 2	Day 3	Day 7	Day 14
C7364	Female	A	Cornea	Opacity	2	2	2	0	0
		B		Area	1	1	1	0	0
		1°) Total (A x B) X5			10	10	10	0	0
		C	Iris		1	1	0	0	0
		2°) Total C x 5			5	5	0	0	0
		D	Conjunctiva	Redness	2	2	2	1	0
		E		Chemosis	2	2	2	1	0
		F		Discharge	2	2	2	0	0
		3°) (D+E+F) x2			12	12	12	4	0
		Totals = 1 + 2 + 3			27	27	22	4	0
		systemic observations			A	A	A	A	A
		Pretest body weight= 2.8 kg

A normal h = lack of normal luster p = panus

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The test article is an eye irritant but not corrosive

Executive summary:

The eye irritation of TIPMDP was tested on 6 female New Zealand Albino rabbits in an eye irritation study following the standards set forth by FHSA, 16 CFR 1500.42. 0.1 ml of the test substane was placed into the conjunctival sac of one eye of each rabbit. The other eye was use as control eye. The eyes were not washed. The eyes were examined and scored by the Draize technique on days 1, 2, 3, 7 and 14. Body weights were recorded pretest. The primary eye irritation score for each rabbit, each day, was calculated. Corneal opacity and iritis, noted in 6/6 eyes, cleared by day 14. Moderate conjunctival irritation, noted in 6/6 eyes, persisted to day 14 in one eye. There were no abnormal physical signs noted during the observation period. The test substance is an eye irritant but not corrosive.