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Description of key information

Guideline acute oral, dermal and inhalation toxicity studies were identified. The L50 / LC50 values determined were as follows:
Oral           - 7600 mg/kg
Dermal      - > 4300 mg/kg
Inhalation - 4100 mg/m3

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Read across justification included in Section 13
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system 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
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
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:
other: 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
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it is GLP compliant and was generally conducted according to OECD 403 guidelines.
Justification for type of information:
Read across justification included in Section 13
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Kingston, New York 12484
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: 222 to 317 grams (males), 185 to 246 grams (females)
- Housing: Individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 to 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24 °C
- Humidity (%): 24 to 91%
- Air changes (per hr): 23 to 28 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: March, 1986 To: June, 1986
Route of administration:
other: inhalation: aerosol and vapour mixture
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Nominal concentrations of test article for each exposure determined gravimetrically. Analytical concentration determined using a gravimetric procedure for aerosol level and MIRAN for the vapour level. Actual exposure level is the sum of the aerosol and vapour level. Actual concentrations of the airborne test article measured near the breathing zone at one hour intervals during the exposure period. Particle size distribution measurements made near the breathing zone at one-hour intervals during the exposure period.

The Plexiglas exposure chamber had a total volume of 100L. The airflow rate (1pm) was 17.5, the air change (min) was 5.7 and the equilibrium time (min) was 26.3.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2.3, 3.5, or 4.9 mg/L
No. of animals per sex per dose:
Ten
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily observations of test animals, weekly weighing of test animals
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Sex:
female
Dose descriptor:
LC50
Effect level:
3.6 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
5.4 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4.1 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
Mortality was seen at all doses, within three days following exposure. 11 animals died at the highest dose; 10 animals died at the middle dose; 1 animal died at the lowest dose.
Clinical signs:
other: Signs included labored breathing and gasping during exposure, which continued in the week following exposure, as well as reduced activity, eyes closed, oral and nasal discharge, and matted coats. All surviving animals were normal by day 15.
Body weight:
Body weight gain was decreased in all surviving animals, but values at day 15 generally indicated recovery from treatment.
Gross pathology:
Discoloration of lungs, red staining around snout on spontaneously dying animals.
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The inhalation LC50 was determined to be 5.4 mg/L in males, 3.6 mg/L in females, and 4.1 mg/L in combined sexes. The test material is classified as harmful by inhalation according to EU criteria.
Executive summary:

In an acute inhalation toxicity study, groups of young adult Sprague-Dawley rats (10 per sex) were exposed by inhalation route to naval distillate for 4 hours at 2.3, 3.5, or 4.9 mg/L of aerosol. Animals then were observed for 14 days.

 

Animals had laboured breathing and nasal discharge, but survivors were normal by study termination. Following exposure, animals in all groups lost weight, but body weight at study termination indicated recovery. The inhalation LC50 was determined to be 5.4 mg/L in males, 3.6 mg/L in females, and 4.1 mg/L in combined sexes. The test material is classified as harmful by inhalation according to EU criteria.

 

This study received a Klimisch score of one and is classified as reliable without restrictions because the study was GLP compliant and was generally conducted according to OECD 403 guidelines.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
4 100 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1979-09-19 to 1979-10-04
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 434.
Justification for type of information:
Read across justification included in Section 13
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: L.I.T. Rabbitry
- Age at study initiation: adult
- Weight at study initiation: 2.0 to 2.5 kilograms
- Fasting period before study: no
- Housing: individually housed in stainless steel laboratory cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: one week


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
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: rabbit's back
- % coverage: 30%
- Type of wrap if used: plastic wrap secured with porous adhesive tape, the entire trunk was wrapped with elastic tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was wiped to remove excess test material
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 mL
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes
- For solids, paste formed: no


VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle used
- Concentration (if solution): no vehicle used
- Lot/batch no. (if required): no vehicle used
- Purity: no vehicle used
Duration of exposure:
24 hours
Doses:
5 mL of undiluted test material
No. of animals per sex per dose:
4 males and 4 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: measured on days 0, 7, and 14
- Necropsy of survivors performed: yes
Preliminary study:
none performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Remarks on result:
other: approx > 4300 mg/kg bw/day
Mortality:
No rabbits died during the study.
Clinical signs:
other: During the 14 day study, erythema followed by a drying and flaking of the skin was observed at the test site in all test rabbits. No signs of systemic toxicity were noted.
Gross pathology:
The gross post-mortem examinations at 14 days revealed four rabbits with congested kidneys, two with haemorrhages in the trachea, and one with a congested liver. None of these observations were found to be treatment-related.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 for diesel fuel was > 5 mL/kg bw (approx 4300 mg/kg bw).
Executive summary:

In an acute dermal toxicity study, 4 male and 4 female New Zealand white rabbits were shaved 24 hours prior to application of test material. This area constituted 30% of the total body surface area. Afterwards, the animals were returned to their stock cages for 24 hours to allow the skin to heal. On testing day, the exposure sites of four animals (2 males and 2 females) were abraded. Minor abrasions were made through the stratum corneum, but not the dermis. A single dose of 5 mL of undiluted test material per kilogram body weight was applied to gauze sponges backed with plastic wrap to help prevent evaporation of the test material. The sponges and plastic wrap were then taped to the shaved area of the rabbit's backs with adhesive tapes. The entire trunk was wrapped with elastic tape and the rabbits were then returned to their cages. After 24 hours, the bandaging was removed and the skin wiped with gauze sponges to remove excess test material. Animals were observed for mortality, local reactions, and behavioural abnormalities daily for 14 days. Body weights were recorded on days 0, 7, and 14. on day 14 all surviving rabbits were subjected to gross necropsy.

During the 14 day study, erythema followed by a drying and flaking of the skin was observed at the test site in all test rabbits. No signs of systemic toxicity were noted. None of the rabbits lost weight during the testing period. The gross post-mortem examinations at 14 days revealed four rabbits with congested kidneys, two with haemorrhages in the trachea, and one with a congested liver. None of these observations were found to be treatment-related. The test material is classified as practically nontoxic.

This study has a Klimisch score of 1 and is classified as reliable without restriction because it was conducted according to or similar to guideline study OECD 434.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute toxicity data are available for oral, dermal and inhalation routes. The L50 / LC50 values were as follows:

Oral - 7600 mg/kg

Dermal - > 4300 mg/kg

Inhalation - 4100 mg/m3

Justification for classification or non-classification

The data available do not meet the classification criteria for acute oral and dermal toxicity.

Data on acute inhalation indicate that that material warrants classification as Category 4 inhalation.