Fusel oil

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study that contains sufficient key data to indicate that the results can be considered reliable.

Data source

Reference

Reference Type:

publication

Title:

Increased ethanol toxicity in old rats: changes in LD50, in vivo and in vitro metabolism, and liver alcohol dehydrogenase activity.

Author:

Wiberg, G., Trenholm, H., Coldwell, B.

Year:

1970

Bibliographic source:

Toxicol. Appl. Pharmacol. 16:718-727.

Materials and methods

Principles of method if other than guideline:

The study followed the basic principles of an OECD 401 study, apart from the fact that the route was ip rather than oral. Observations were for only 24 hours, no necropsy and histopathology reported as carried out. Two series of experiments were carried out, one at constant dosing volume and one at constant dosing concentration.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethanol

EC Number:

200-578-6

EC Name:

Ethanol

Cas Number:

64-17-5

Molecular formula:

CH3CH2OH

IUPAC Name:

ethanol

Details on test material:

- Name of test material (as cited in study report): No data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Woodlyn Farms, Guelph, Ontario.
- Age at study initiation: young animal cohort: 100 days old. Old animal cohort: 10 - 12 months.
- Fasting period before study: overnight
- Housing: individually in stock cages.
- Diet: ad libitum, standard lab chow (ex Master Fox Cubes, Toronto Elevators Ltd)
- Water: ad libitum, tap

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

water

Details on exposure:

Constant concentration series: 15% w/v solution.
Constant volume series: concentrations for younger animals 24-28%., for older animals 17-22%
Dose interval used 1.05.

Doses:

- Doses: Not stated but 6 to 8 dose levels with interval 1.05.
- Doses per time period: One
- Exposure duration: not applicable.

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 24 hours
- Necropsy not conducted

Statistics:

LD50 estimated by the moving average method of Weil (Biometrics, 8, 249, 1952) or by the graphical technique of Litchfield and Wilcoxon (J Pharmacol Exp Ther, 96, 99, 1949)

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

6 710 mg/kg bw

95% CL:

> 6 310 - < 7 130

Remarks on result:

other: young animals, constant concentration

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

5 100 mg/kg bw

95% CL:

> 5 010 - < 5 140

Remarks on result:

other: older animals, constant concentration

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

5 500 mg/kg bw

95% CL:

> 5 330 - < 5 620

Remarks on result:

other: younger animals, constant volume

Effect levels 4

Sex:

male

Dose descriptor:

LD50

Effect level:

4 070 mg/kg bw

95% CL:

> 3 870 - < 4 280

Remarks on result:

other: older animals, constant volume

Mortality:

Time of death: All within 24 hour, individual times not reported.

Clinical signs:

Description, severity, time of onset and duration of clinical signs at each dose level: not reported.

Body weight:

no data

Gross pathology:

no data

Other findings:

- Necropsy findings, included doses affected, severity and number of animals affected: not conducted.
- Potential target organs: cause of death was respiratory failure.

Applicant's summary and conclusion

Conclusions:

Toxicity does not appear to be solely related to concentration. Dilute solutions are less toxic.

Executive summary:

An acute toxicity study using intraperitoneal dosing examined the effect of age of male rats on the oral LD50. Using a relatively large number of animals and 6 -8 doses at a constant gavage volume, an LD50 value of 5500mg/kg was obtained for young animals (~100 days old) whereas a significantly lower figure of 4070mg/kg was obtained for older rats (~11 -12 months old). A second study used a constant dosing concentration (variable volume) and derived LD50 values approximately 25% higher, suggesting that dilute solutions are less toxic. Animals were only observed for a period of 24 hours, although it is unlikely that significant deaths would have occured after this point due to the known toxicokinetics of metabolism. For those animals that died death was due to respiratory failure.