Acetic anhydride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP compliant, near guideline study, available as unpublished report, adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Principles of method if other than guideline:

5 animals per gender per group
Starved for 16 hours before administration of the test material.
Single oral gavage administration
Seven dose levels.
Animals monitored over 14 days.
Autopsy of animals that died during study
Survivors sacrificed at study termination, then autopsy.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

SPF-bred: WIGA, Sulzfeld
mean staring weight males = 254g
mean starting weight females = 190g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

Emulsion in olive oil

Details on oral exposure:

formulated from 3.16 - 31.6 % in olive oil.

Doses:

316, 464, 681, 1000, 1470, 2150, 3160 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

5 animals per gender per group. Single oral dose using 7 dose levels .
Animals monitored over 14 days and symtoms and deaths recorded at 1 hour, 24 hours, 48 hours, 7 days and 14 days post dose.
At the end of the 14 days the animals were killed following exposure to CO2 prior to examination of major internal organs.
Animals that died during the study were autopsied.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

630 mg/kg bw

Mortality:

Death usually occurred within 24 hours of dosing.

Clinical signs:

other: Toxic signs included dyspnoea. apathy, lying down, staggering, shaking, trembling, diarrhoea, hypertension, arched back and general poor condition.

Gross pathology:

Animals that died during the study - heart: acute dilation; acute inflamation. Stomach: hardened lining and bloody ulceration. GI tract with redenned membranes.
Surviving animals - Stomach: ulcerative spots. Adhesions of the forestomach, liver, spleen, diaphram and peritoneum.

Any other information on results incl. tables

Mortality

Dose	Concentration	Number of Animals	Mortality within
mg/kg	%		1 hour	24 hours	48 hours	7 days	14 days
3160	31.6	5 male	0/5	5/5	5/5	5/5	5/5
		5 female	0/5	5/5	5/5	5/5	5/5
2150	21.5	5 male	0/5	5/5	5/5	5/5	5/5
		5 female	0/5	5/5	5/5	5/5	5/5
1470	14.7	5 male	0/5	5/5	5/5	5/5	5/5
		5 female	0/5	5/5	5/5	5/5	5/5
1000	10	5 male	0/5	3/5	3/5	3/5	3/5
		5 female	0/5	3/5	3/5	3/5	3/5
681	6.81	5 male	0/5	1/5	1/5	1/5	1/5
		5 female	0/5	5/5	5/5	5/5	5/5
464	4.64	5 male	0/5	0/5	0/5	0/5	0/5
		5 female	0/5	1/5	1/5	1/5	2/5
316	3.16	5 male	0/5	0/5	0/5	0/5	0/5
		5 female	0/5	0/5	0/5	0/5	0/5

Applicant's summary and conclusion

Executive summary:

The LD50 of acetic anhydride in rats was estimated to be 630 mg/kg bodyweight following oral, gavage, administration of the test material.