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

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

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

Details on test material:

- Name of test material (as cited in study report): 3,4-diaetoxy-1-butene
- Physical state: Clear,colorless liquid
- Purity: >99%, The purity and stability of the test substance were determined by the Chemical Quality Services Division
- Stability under test conditions: The purity and stability of the test substance were determined by the Chemical Quality Services Division

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: strain Swiss CD-l, Cr1 :CD-1®(ICR)BR, were received from Charles River Laboratories Inc ., Raleigh, NC .
- Age at study initiation: 47 days
- Weight at study initiation: 19 .88 g to 26 .72 g
- Fasting period before study: no data
- Housing: The mice were housed two or three per cage in suspended, stainless-steel, wiremesh cages. Cages and racks were washed once per week . Absorbent paper, used to collect excreta, was changed at least three times per week.
- Diet (e.g. ad libitum): commercial diet, PMI certified rodent diet 5002 pellets. The feed was analyzed by the manufacturer for concentrations of specified heavy metals, aflatoxin, chlorinated hydrocarbons, organophosphates, and specified nutrients.
- Water (e.g. ad libitum): water were available ad libitum for the duration of the study
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 41-56
- Air changes (per hr): no details
- Photoperiod (hrs dark / hrs light): photoperiod of 12 hours, from 6a.m. to 6 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil

Duration of treatment / exposure:

animals were dosed with the test substance and were euthanatized at 24 and 48 hours after dosing for extraction of the bone marrow

Frequency of treatment:

single treatment

Post exposure period:

24h and 48h

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 500, 1000, and 2000 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

- Route of administration: oral gavage
- Doses / concentrations: 80 mg/kg
cyclophosphamide was included only at the 24-hour sampling time.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

In the preliminary study, it was determined that the LD 50/3 of the test substance in male and

female mice was > 2000 mg/kg, the maximum dose level suggested in the OECD Guideline

474 for the mouse micronucleus assay .

In the main study, one male in the high-dose group exhibited signs of hypothermia and impaired respiration, and died

on the day following dosing . In order to maintain equal numbers of animals in all dose groups,

this animal was replaced for femur harvest with an additional animal that had been dosed at

2000 mg/kg . Clinical signs in the other animals included decreased feces output in high-dose

females, and weakness in three males from the high-dose group ; all three of these males

became moribund following the observed weakness . It is known that the moribund condition of

these males did not affect the outcome of the study because the PCE/NCE ratios for each of

these animals was similar to other animals in the study .

Statistical analysis revealed a statistically significant trend for depression in bone marrow

among the female groups at the 24 hour sacrifice with respect to dose . Although no single

value was significantly different from the negative control, this trend provides direct evidence

of bone marrow exposure to the test substance. The positive control groups,

treated with 80 mg/kg cyclophosphamide, showed significant bone marrow depression when

compared with the negative controls . No significant effect of the test substance on micronuclei

per 1000 PCE was detected . By contrast, the animals treated with 80 mg/kg cyclophosphamide

showed highly significant increases in micronucleated PCEs as compared with the negative

control, and statistically significant decreases in percent PCE (bone marrow depression) at 24

hours for both the male and female groups .