Acetic anhydride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 12 1995 to Feb 7 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, available as unpublished report. No restrictions, fully adequate for assessment.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 413

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Acetic anhydride

EC Number:

203-564-8

EC Name:

Acetic anhydride

Cas Number:

108-24-7

Molecular formula:

C4H6O3

IUPAC Name:

acetyl acetate

Details on test material:

- Name of test material (as cited in study report): acetic anhydride
- Physical state: liquid
- Analytical purity: 99% +
- Purity test date: Responsibility of sponsor
- Lot/batch No.: 50218009
- Expiration date of the lot/batch: Responsibilty of Sponsor
- Storage condition of test material: Ambient temperature, dry.

Test animals / tissue source

Species:

rat

Strain:

other: CD (Sprague Dawley)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Manston Rd, Margate, Kent, UK.
- Age at study initiation: 7-8 wks at randomisation
- Weight at study initiation: 227g (males), 184 g (females)
- Age at start of exposures: 10-11 wks
- Housing: 5/cage (same sex) in suspended stainless steel cages with wire mesh front, back and floor and stainless steel sheet sides.
- Diet (e.g. ad libitum): SDS Rat & Mouse no. 1 SQC modified maintenance diet, Special Diet Services, Witham, Essex, UK.
- Water (e.g. ad libitum): Tap water provided in ploypropylene bottles
- Acclimation period: 4 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 ºC
- Humidity (%): 40-65 %
- Air changes (per hr): No details. Cages for each test group kept in separate ventilated cabinets.
- Photoperiod (hrs dark / hrs light): 12/12 (0730-1930)

IN-LIFE DATES: From: 12 July 1995 To: 7 February 1996

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

1, 5, 20 ppm Target concentration
0.98, 4.96, 20.0 ppm Analytical concentration
1.23, 6.5, 26.3 ppm Nominal concentration

Duration of treatment / exposure:

6 hrs/day, 5 days/week for 13 weeks

Observation period (in vivo):

13 weeks treatment; 13 weeks post-exposure

Number of animals or in vitro replicates:

15/sex/group (including 5/sex/group for withdrawal period)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: Ocular changes were described as part of the clinical observations.

Time point:

other: At least once daily.

Remarks on result:

other: score not provided

Results 2

Irritation parameter:

other: Ophthalmic examination by indirect ophthalmoscope.

Time point:

other: All animals pre-study, all main study animals in week 13, all withdrawal animals in week 26.

Remarks on result:

other: Prior to examination, pupils were dilated using 0.5% Mydriacyl.

Results 3

Irritation parameter:

cornea opacity score

Remarks:

Not measured

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Results 4

Irritation parameter:

iris score

Remarks:

Not measured

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Not measured

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Results 6

Irritation parameter:

chemosis score

Remarks:

Not measured

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Any other information on results incl. tables

Partially closed eyes were observed during the first two expsoures in high dose animals.

During week 13, corneal changes were evident in a number of animals in the intermediate and high doses groups and comprised corneal lack-lustre and corneal opacities (bi-lateral in less than half of the cases). There were no treatment related findings in week 26.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: Clinical signs and ophthalmoscopy

Conclusions:

In the presence of acetic anhydride vapour, reversible ocular irritation with mild corneal effects were reported.

Executive summary:

Following whole-body inhalation exposure to 0, 1, 5 or 20 ppm acetic anhydride for 6hr/day for 13 weeks, signs of eye irritation were seen in 20 ppm animals during the first two exposures only.

Corneal lesions were observed in most animals exposed to 20 ppm and in a few exposed to 5 ppm after 13 weeks of exposure. These findings were consistent with exposure to an irritant or mildly corrosive atmosphere and were not observed histologically. There were no treatment related changes after 13 weeks of withdrawal.