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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 July 2002- 15 August 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: according to OECD principles of GLP and based on OECD no. 401 (1987), available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Furfural
- Physical state: clear yellow liquid
- Analytical purity: >99%
- Lot/batch No.: FF 280302
- Expiration date of the lot/batch: March 28, 2003
- Storage condition of test material: stored in the original container as supplied by the sponsor (i.e. glass bottle) at room temperature.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Breeding facility, Jai Research Foundation
- Age at study initiation: 9-11 weeks at time of dosing
- Weight at study initiation: 199-264 g (males) and 151-194 g (females)
- Fasting period before study: minimum 17 hours and 15 minutes
- Housing: 5 animals of the same sex
- Diet: Rat pellet diet (Amrut brand) (Pranav Agro Industries Ltd., Pune, Maharashtra, India ad libitum (except for the pre-dose fast and for approximately 3 hours after dosing)
- Water: Filtered drinking water ad libitum
- Acclimation period: minimum of 5 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature: 19-24°C
- Humidity: 64-66%
- Air changes: 25/hour
- Photoperiod: 12 hours dark, 12 hours light

IN-LIFE DATES: From: 30 July 2002 To: 15 August 2002

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 7, 10, 12, 14, 20.5 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
Doses:
70, 100, 120, 140, 205 mg/kg
No. of animals per sex per dose:
10 animals per sex per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Examined for mortality and morbidity 1, 2 and 3 hours and once thereafter on the day of dosing, and at least twice per day thereafter. Clinical signs were recorded daily and body weights weekly (days 0, 7 and 14).
- Necropsy of survivors performed: yes
Statistics:
Acute oral LD50 calculated using the probit analysis (Finney DJ, 1971, Probit Analysis, 3rd edition, Cambridge University Press p.333)

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
100 mg/kg bw
Based on:
test mat.
95% CL:
63 - 159
Remarks on result:
other: 5/10 mortalities at 100 mg/kg
Sex:
female
Dose descriptor:
LD50
Effect level:
105 mg/kg bw
Based on:
test mat.
95% CL:
88 - 125
Remarks on result:
other: 4/10 mortalities at 100 mg/kg, 6/10 mortalities at 120 mg/kg
Sex:
male/female
Dose descriptor:
LD50
Effect level:
108 mg/kg bw
Based on:
test mat.
95% CL:
97 - 121
Mortality:
mortality at dose levels
0: males 0/10 females 0/10
70: males 0/10 females 2/10
100: males 5/10 females 4/10
120: males 6/10 females 6/10
140: males 7/10 females 8/10
205: males 10/10 females 10/10
Clinical signs:
Lethargy, tremors, abdominal breathing, tachypnea, exophthalmos, piloerection in some treated animals. Bronchial rales were observed in the 100 and 140 mg/kg dose group.
Lethargy was observed in all the treated animals at all dose levels during the 1 h observation and persisted throughout the dosing day. One animal belonging to 100 mg/kg body weight dose group was found lethargic till 48 h after dosing.
Tremors were observed in 2 animals at 100mg/kg, 1 animal at 120 mg/kg and 5 animals at 140 mg/kg dose levels.
Abdominal breathing was noted in all the animals at 205 mg/kg dose level and in most of the animals from other dose groups during the observation at 1, 2 and 3 h after dosing.
Tachypnea was observed in two animals at 100 mg/kg dose level. Whereas, bronchial rales were noticed in two animals at 100 mglkg and one animal at 140 mglkg dose levels.
Exophthalmos was exhibited by most of the animals from 205, 140, 120 and 100 mg/kg dose groups and by few animals from 70 mg/kg dose group.
Few anirnals 140, 120 and 70 mg/kg dose groups showed piloerection on the day of dosing.
All surviving animals except one from the 100 mg/kg dose group were found normal at 24 h after dosing.
Body weight:
There was a normal increase in the body weight of control and the treated group animals. The per cent body weight changes of treatment groups were at comparable levels with control group for each sex
Gross pathology:
External examination of "found dead" animals revealed froth from nostrils. Terminally sacrificed animals did not reveal any lesion of pathological significance. Visceral examination of "found dead"animals showed prominent lesions in lungs (congestion/ haemorrhage, oedema, consolidation, emphysema); liver (mottling / haemorrhage) and intestine (mucus exudation). These lesions could be considered as test substance related. Terminally sacrificed animals revealed various inflammatory / vascular changes with low level of occurrence which could be considered as spontaneous / incidental findings and unrelated to test substance.

Applicant's summary and conclusion

Conclusions:
In an acute oral toxicity study in rats, LD50 values of 100, 105 and 108 mg/kg bw/day were established for male rats, female rats and combined sexes, respectively.
Executive summary:

In an acute oral toxicity study in rats, to modern guidelines, acute oral LD50 values of 100, 105 and 108 mg/kg bw/day were established for male rats, female rats and combined sexes, respectively.