Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1979-05-22 to 1979-08-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it was conducted according to, or similar to guideline study OECD 420.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity liquid hydrocarbon
Details on test material:
- Name of test material (as cited in study report): API #79-6, diesel fuel
- Substance type: petroleum distillate product composed of hydrocarbon chain
- Physical state: liquid
- Analytical purity: not provided by sponser
- Impurities (identity and concentrations): not reported
- Composition of test material, percentage of components: 41.7% paraffins, 30.9% cycloparaffins, 27.4% aromatics
- Isomers composition: not reported
- Purity test date: not reported
- Lot/batch No.: not reported
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not provided by sponser
- Storage condition of test material: test test material was stored in Elar's test material storage room

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: you adults
- Weight at study initiation: 200 to 400 g
- Fasting period before study: feed was withheld overnight prior to dosage
- Housing: housed individually in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: two weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported


IN-LIFE DATES: not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no vehicle
- Amount of vehicle (if gavage): no vehicle
- Justification for choice of vehicle: no vehicle
- Lot/batch no. (if required): no vehicle
- Purity: no vehicle


MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg


DOSAGE PREPARATION (if unusual): not reported


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: N/A
Doses:
2.5, 5, 10, 15, and 20 mL/kg
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weight was recorded on days 0, 7, and 14
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
9 mL/kg bw
95% CL:
>= 5.58 - 14.51
Remarks on result:
other: approx 7600 mg/kg bw
Mortality:
Mortality rates of the five dose groups (2.5, 2.0, 10, 15, and 20 mL/kg) were 12.5, 20, 70, 40, and 90% respectively.
Clinical signs:
Clinical signs observed were oily urine stains and oily diarrhoea, which resulted in hair loss, irritation, redness, and sores. In many cases, the anal area had open sores. In the highest dose (20 mL/kg) the entire ventral side and legs were affected. In some instances there was blood around the eyes, nose, and mouth. Other symptoms noted included lethargy, pus, or blood at the urinary orifice.
Body weight:
weight gain/loss ranged from:
-12 to +74 in the 2.5 mL/kg dose
-18 to +54 in the 5 mL/kg dose
-58 to +15 in the 10 mL/kg dose
-95 to +17 in the 15 mL/kg dose
-50 to 46 in the 20 mL/kg dose
Gross pathology:
Rats that survived for the duration of the study had few abnormalities and abnormal signs that were observed included enlarges Peyer's patched on the intestine. In both surviving animals and those that died prematurely, many exhibited mild irritation in their lungs or congestion to fluid filled abcesses. In the animals that died prematurely, almost all had intestinal damage including hemorrhaging in the stomach and thinning of the intestinal walls. A few rats has white spots on their caecums and increased gas was noticed in the gastrointestinal tract.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test material had an oral LD50 of 9.0 mL/kg (approx 7600 mg/kg) body weight. The test material is not classified according to EU criteria.
Executive summary:

In an acute oral toxicity study, five groups of ten rats (5 males and 5 females) were given a single dose of the appropriate amount of diesel fuel (marketplace sample) (2.5, 5.0, 10, 15, or 20 mL/kg) via oral gavage. Dose levels were chosen to produce expected mortality rates between 10 and 90%. Signs of mortality and toxicity were observed daily for the duration of the study (14 days). Body weight was measured on days 0 and 7, and upon death. Gross necropsy was performed on each animal when they died or by day 14.

Mortality rates of the five dose groups (2.5, 5, 10, 15, 20 mL/kg) were 12.5, 20, 70, 40, and 90% respectively. Signs of toxicity were observed in all dose groups. Severity increased with increased dose. Clinical signs observed were oily urine stains and oily diarrhoea, which resulted in hair loss, irritation, redness, and sores. In many cases, the anal area had open sores. In the highest dose (20 mL/kg) the entire ventral side and legs were affected. In some instances there was blood around the eyes, nose, and mouth. Other symptoms noted included lethargy, pus, or blood at the urinary orifice. Gross pathology observations were also similar in each dose group. In rats who survived for the duration of the study (14 days), there were few abnormalities. In these rats minor observations included enlarged Peyer's patches on intestines. Both animals that died and survived exhibited mild irritation and congestion in the lungs, in addition to fluid-filled abscesses in the lungs. The majority of the animals that died before day 14 showed intestinal damage including, hemorrhaging, thinning of intestinal walls, and increased gas in the gastrointestinal tract.

Under the conditions of this study, the test material had an oral LD50 of 9.0 mL/kg (approx 7600 mg/kg) and a 95% confidence interval of 5.58 and 14.51 mL/kg. the test material was determined to have a median lethal dose according to the study report. The test material is not classified according to EU criteria.

This study received a Klimisch score of 1and is classified as reliable without restriction because it was conducted similar to guideline study OECD 401.