Reaction mass of 1,2-Diacetoxy-3-butene and 1,2-Dihydroxy-3-butene, monoacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented guideline study conducted under GLP-conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-Butene-1,2-diol, diacetate

IUPAC Name:

3-Butene-1,2-diol, diacetate

Constituent 2

Reference substance name:

1,2-diacetoxybut-3-ene

EC Number:

421-720-5

EC Name:

1,2-diacetoxybut-3-ene

Cas Number:

18085-02-4

Molecular formula:

C8 H12 O4

IUPAC Name:

1,2-diacetoxybut-3-ene

Constituent 3

Reference substance name:

DIACETOXYBUTENE

IUPAC Name:

DIACETOXYBUTENE

Details on test material:

- Name of test material (as cited in study report): 3,4-DIACETOXY-1-BUTENE
- Physical state: Liquid, clear/colorless
- Other: Source: Eastman Kodak Chemical Company

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Crl:CD(SD)BR VAF plus; Charles River Kingston (Stone Ridge, NY)
- Age at study initiation: male rats were 6 weeks of age; female rats were 7 weeks of age
- Weight at study initiation: male rats weighed 129 to 157 grams; female rats weighed 135 to 162 grams
- Fasting period before study: overnight before single dose gavage
- Housing: rats were singly housed in suspended, stainless-steel, wire mesh cages. Cages and racks were washed once a week. Absorbent paper, used to collect excreta, was changed at least three times a week.
- Diet (e.g. ad libitum): Certified Rodent Diet (PMI® #5002, pelleted) was available ad libitum
- Water (e.g. ad libitum): Water was available ad libitum through an automatic watering system
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 54-61
- Air changes (per hr): no details
- Photoperiod (hrs dark / hrs light): photoperiod of 12 hours light from 6 a.m. to 6 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The test subst ance, a liquid, was administered as received

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on results of a range-finding test, doses of 500, 1000, and 2000 mg/kg of the test substance were selected as the dose levels for the oral toxicity study .

Doses:

500, 1000 and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were collected on Days 0(prior to treatment), 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed:
1. clinical signs: Animals were observed three times on the day of dosing (Day 0), and once each day thereafter for the duration of the experiment . Observations included, but were not limited to, examination of the hair, skin, eyes, mucous membranes, motor activity, feces, urine, respiratory system, circulatory system, autonomic nervous system, central nervous system, and behavior patterns.
2. other: necropsy: Any animal that died during the study was necropsied as soon as possible. All surviving animals were euthanatized and necropsied at the completion of the 14-day observation period .

Statistics:

No dose/mortality curve was constructed since graphs become statistically useful only with the use of large numbers of animals and dose groups . No furhter data given.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

794 mg/kg bw

95% CL:

483 - 1 305

Remarks on result:

other: combined LD50

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

891 mg/kg bw

95% CL:

451 - 1 759

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

707 mg/kg bw

95% CL:

318 - 1 574

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 5
Male: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 2
Male: 500 mg/kg bw; Number of animals: 5; Number of deaths: 2
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 5
Female: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 3
Female: 500 mg/kg bw; Number of animals: 5; Number of deaths: 2

Clinical signs:

other: Signs of toxicity related to dose levels: Clinical signs observed during the 14-day observation period included slight to severe weakness, vasodilation, and reduced feces. Severe weakness was noted only in animals assigned to the 2000 mg/kg dose group,

Gross pathology:

Effects on organs: The cause of death for the rats which died after treatment with the test substance was not determined. The treatment-
related changes observed at necropsy for the 2000 mg/kg animals and for the 1000 mg/kg female rats, which died within 24 hours of dosing, consisted of minimal to moderate hemorrhage in the glandular gastric mucosa. No treatment- related changes were observed at necropsy for the remaining
1000 mg/kg animals for any 500 mg/kg animals.

Any other information on results incl. tables

The test substance was a gastric tract irritant as evidenced by hemorrhage in the glandular gastric mucosa of rats from the 1000 and 2000 mg/kg bw dose groups. The acute oral LD50 for this test substance was calculated to be 891 mg/kg bw for male rats and 707 for female rats. Based on the oral LD50 calculated by combining the male and female mortality data (794 mg/kg bw), the test substance was classified as slightly toxic in rats according to the criteria set forth by Hodge and Sterner (1949) and harmful if swallowed as defined in the 18th Adaptation on the EC Classification, Packaging, and Labeling of Dangerous Substances.

Table 1: Results from the acute oral study (body weights)

 

Dose mg/kg bw	Day 0	Day 7	Day 14
Male rats
500	136	Died Day 1	/
500	137	222	284
500	138	Died Day 1	/
500	151	246	316
500	157	255	320
1000	145	Died Day 1	/
1000	129	Died Day 1	/
1000	146	236	306
1000	155	240	317
1000	146	207	297
2000	151	Died Day 1	/
2000	143	Died Day 1	/
2000	154	Died Day 1	/
2000	142	Died Day 1	/
2000	143	Died Day 1	/
Female rats
500	148	213	245
500	138	189	217
500	135	203	231
500	145	Died Day 1	/
500	147	Died Day 1	/
1000	148	Died Day 1	/
1000	157	Died Day 1	/
1000	161	205	245
1000	162	Died Day 1	/
1000	154	214	247
2000	146	Died Day 1	/
2000	142	Died Day 1	/
2000	147	Died Day 1	/
2000	144	Died Day 1	/
2000	144	Died Day 1	/