Etidronic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study meets generally accepted scientific principles, but was not conducted in compliance with GLP.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1965

Report date:

1965

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Method: other: Insufficient detail to fully assess comparability with OECD guideline.

GLP compliance:

no

Remarks:

Conducted prior to adoption of GLP

Test material

Test material information

Constituent 1

Reference substance name:

Etidronic acid

EC Number:

220-552-8

EC Name:

Etidronic acid

Cas Number:

2809-21-4

Molecular formula:

C2H8O7P2

IUPAC Name:

(1-hydroxyethane-1,1-diyl)bis(phosphonic acid)

Test animals / tissue source

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


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


IN-LIFE DATES: No data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Amount applied: 0.1 ml (although the recommended dose of 0.1 ml was achieved for the formulation, this means that the limit dose for the active
acid was not attained).

Duration of treatment / exposure:

up to 24 hour(s)

Observation period (in vivo):

Seven days (skin reactions scored at 1, 24, 48, 72, 120 and 168 hours)

Number of animals or in vitro replicates:

Three

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, all animals with warm isotonic saline
- Time after start of exposure: 24 hours for animals 1 and 2, and four seconds for animal 3.


SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: No data

Results and discussion

In vivo

Results

Irritation parameter:

other: maximum irritation score

Basis:

animal: average of1 and 2

Time point:

other: from all time points

Score:

ca. 90

Max. score:

110

Reversibility:

not reversible

Remarks on result:

other: 24 hours exposure

Irritant / corrosive response data:

24 hour exposure: Copious discharge, translucent cornea with iris details moderately obscured, particularly the lower half, moderately severe erythema, and swelling with partial eversion of the lids developed within one hour of instillation. After 24 and 48 hours corneal opacity increased and the conjunctivae became bright red. The lower half of the cornea became opaque within 72 hours and remained so throughout the seven day observation period. With the lower portion of the iris invisible and not responding to light, it was evident that sight had been destroyed. The upper half of the eye was only moderately affected due to the fact that the dose was concentrated in the conjunctival sac.

4 second exposure: After one hour there was moderate lacrimation, mild oedema and erythema, and mild corneal cloudiness with iris details clearly visible. Congestion increased slightly by 24 hours, but decreased thereafter with only very slight redness remaining after seven days.

Other effects:

Discomfort immediately following instillation.

Any other information on results incl. tables

Table 1 Summary of Eye Irritation

Animal	Evaluation time point
	1	24	48	72	120	168
24 hour exposure
1	42	57	75	90	90	90
2	49	69	83	90	90	90
Average	45.5	63	79	90	90	90
4 second exposure
3	31	36	29	22	13	4

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In an eye irritation study (reliability score 2) conducted prior to the adoption of OECD test guidelines and GLP, Dequest 2010 was corrosive to the eyes of rabbits.

Executive summary:

In an eye irritation study (reliability score 2) conducted prior to the adoption of OECD test guidelines and GLP, 0.1 ml undiluted Dequest 2010 was placed into the conjunctival sac of the right eye of each of three albino rabbits. The eyes of animals 1 and 2 were rinsed with warm isotonic saline after 24 hours exposure. The eye of animal 3 was washed after four seconds. Observations were made for seven days, and reactions scored according to the method of Draize. After 24 hours exposure there was copious discharge, translucent cornea with iris details moderately obscured, particularly the lower half, moderately severe erythema, and swelling with partial eversion of the lids developed within one hour of instillation. After 24 and 48 hours corneal opacity increased and the conjunctivae became bright red. The lower half of the cornea became opaque within 72 hours and remained so throughout the seven day observation period. With the lower portion of the iris invisible and not responding to light, it was evident that sight had been destroyed. The upper half of the eye was only moderately affected due to the fact that the dose was concentrated in the conjunctival sac. After a four second exposure moderate lacrimation, mild oedema and erythema, and mild corneal cloudiness with iris details clearly visible were observed within an hour. Congestion increased slightly by 24 hours, but decreased thereafter with only very slight redness remaining after seven days. Dequest 2010 was considered to be corrosive to the eyes of rabbits.