3,5-dichlorobenzoyl chloride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1969

Report date:

1969

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,5-dichlorobenzoyl chloride

EC Number:

220-813-6

EC Name:

3,5-dichlorobenzoyl chloride

Cas Number:

2905-62-6

Molecular formula:

C7H3Cl3O

IUPAC Name:

3,5-dichlorobenzoyl chloride

Test material form:

other: granular

Details on test material:

- Appearance: White, granular solid with a faint odour which formed a liquid when heated to 30 °C for the purpose of administration.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Adult
- Weight at study initiation: 2.0 - 3.1 kg
- Diet (e.g. ad libitum): Purina Rabbit Chow available ad libitum.
- Water (e.g. ad libitum): Water available ad libitum.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL.

Duration of treatment / exposure:

A single treatment.

Observation period (in vivo):

14 days.

Number of animals or in vitro replicates:

9

Details on study design:

The eyes were judged free of irritation and corneal damage (confirmed by sodium fluorescein examination) prior to initiation of the study.

Administration: A single application of 0.1 mL was made into the conjunctival sac of the left eye of nine rabbits. Three eyes were irrigated with 20 mL of tap water two seconds after application, three eyes were irrigated four seconds after application, and three eyes were not irrigated but were held closed for one second. Untreated right eyes served as controls.

Observations and Records:

Gross Signs of Eye Irritation and Systemic Toxicity - Observations recorded at 24, 48, and 72 hours and 4, 7, 10, and 14 days following application. Eye irritation graded and scored according to the numerical scoring system of Draize (see below).
Body Weights - Recorded initially and terminally.
Terminal Fluorescein Examination: On Day 7, Day 10, or Day 14, treated eyes were examined with 2.0% sodium fluorescein stain for evidence of corneal damage.


SCORING SYSTEM: Draize Scale for Ocular Irritation.

Draize Scale for Scoring Ocular Irritation

1. CONJUNCTIVAE

(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal............................................................................................................................................0
Vessels definitely injected above normal................................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red.........................................................................................................................................3

(B) Chemosis
No swelling..................................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids.......................................................................................2
Swelling with lids about half closed.........................................................................................................3
Swelling with lids half closed to completely closed...............................................................................4

(C) Discharge
No discharge...............................................................................................................................................0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals)......................................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids...............................................2
Discharge with moistening of the lids and hairs a considerable area around the eye...................3

THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20

2. IRIS

(D) Values
Normal.........................................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these orcombination of any thereof) iris still reacting to light
(sluggish reaction is positive).................................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10

3. CORNEA

(E) Degree of Opacity (most dense area used)
No opacity...................................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible......................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity................................................................................4

(F) Area of Cornea Involved
One quarter (or less) but not zero..........................................................................................................1
Greater than one quarter but less than half...........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.......................................................................................4

THE TOTAL SCORE =(E x F) x 5 MAXIMUM TOTAL = 80

MAXIMUM TOTAL SCORE POSSIBLE = 110

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: No numerical values reported.

Remarks:

Reported as slight to moderate conjunctival erythema subsiding by day 14.

Results 2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: No numerical values reported.

Remarks:

Reported as slight chemosis subsiding by day 10

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: No numerical values reported.

Remarks:

Reported as corneal opacity at 24 hours

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks on result:

other: No numerical values reported.

Remarks:

Reported as slight iritis subsiding by day 4

Any other information on results incl. tables

Principal Toxic Effects - None considered related to mucous membrane absorption; however, blinking and preening of the treated eye was noted immediately following instillation. Slight terminal weight loss was also observed in four animals.

Gross Signs of Eye Irritation

-Irrigated Groups: From 24 hours, irritation included slight to marked (one eye) conjunctival erythema (subsiding by day 10), slight chemosis and discharge (subsiding by 72 hours or in one eye by day 7), and slight iritis (at 24 hours). A red spot on the iris of one eye was noted from 48 hours through day 10 but could possibly have been a self-inflicted injury.

-Non-irrigated Group: From 24 hours, irritation included slight to moderate conjunctival erythema (subsiding by day 14), slight chemosis (subsiding by day 10), slight to moderate discharge (subsiding by day 10), slight iritis (subsiding by day 4), and in one eye slight corneal opacity at 24 hours. On day 10 and day 14, alopecia surrounding the eye was observed in two animals.

-Terminal Fluorescein Examination - On day 7, day 10, or day 14, the examination confirmed the absence of corneal damage in all treated eyes.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Not possible to determine classification with available information. Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of this study, the test material caused some eye irritation with no sign of toxic effects. All symptoms were fully recovered by the end of the observation period.

Executive summary:

The potential of the test material to cause eye irritation in the New Zealand White rabbit was investigated in a study which was conducted using methodology broadly equivalent to the standardised guideline OECD 405.

A single application of 0.1 mL was made into the conjunctival sac of the left eye of nine rabbits. Three eyes were irrigated with 20 mL of tap water two seconds after application, three eyes were irrigated four seconds after application, and three eyes were not irrigated but were held closed for one second. Untreated right eyes served as controls.

Observations for gross signs of eye irritation and systemic toxicity were made at 24, 48, and 72 hours and 4, 7, 10, and 14 days following application. Eye irritation was graded and scored according to the Draize scale.

Blinking and preening of the treated eye was noted immediately following instillation.

-Irrigated Groups: From 24 hours, irritation included slight to marked (one eye) conjunctival erythema (subsiding by day 10), slight chemosis and discharge (subsiding by 72 hours or in one eye by day 7), and slight iritis (at 24 hours).

-Non-irrigated Group: From 24 hours, irritation included slight to moderate conjunctival erythema (subsiding by day 14), slight chemosis (subsiding by day 10), slight to moderate discharge (subsiding by day 10), slight iritis (subsiding by day 4), and in one eye slight corneal opacity at 24 hours. On day 10 and day 14, alopecia surrounding the eye was observed in two animals.

Terminal fluorescein examination confirmed the absence of corneal damage in all treated eyes.

Under the conditions of this study, the test material caused some eye irritation with no sign of toxic effects. All symptoms were fully recovered by the end of the observation period.