Petroleum kerosene fraction, co-processed with renewable hydrocarbons of plant and/or animal origin

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

1985-01-24 to 1985-02-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restrictions because it was carried out in a method similar/equivalent to OECD TG 412.

Justification for type of information:

Read across justification included in Section 13

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

1985-01-24 to 1985-02-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restrictions because it was carried out in a method similar/equivalent to OECD TG 412.

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 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

yes

Remarks:

Only one dose tested

GLP compliance:

yes

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., Portage, Michigan
- Age at study initiation: Approximately 6 weeks old
- Weight at study initiation: Males: 126 to 191 grams; Females: 111 to 161 grams
- Fasting period before study: No
- Housing: Each group was maintained in a 1 m3 exposure chamber made of glass and stainless steel. Ten rats were held per cage batteries which were arranged in two tiers of two batteries within each exposure chamber.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 26
- Humidity (%): 20 to 60%

IN-LIFE DATES: From: 1985-01-24 To: 1985-02-22

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposure chamber
- Method of holding animals in test chamber: In cages
- Source and rate of air: HVAC system separate from the general laboratory system
- System of generating particulates/aerosols: Spraying Systems atomizer (No. 64 SS air nozzle, No. 1650 SS liquid nozzle, 1/4 J SS body)
- Air flow rate: 200-240 L/min


TEST ATMOSPHERE
- Brief description of analytical method used: Exposure concentration was determined with a Scott Model 216 Total Hydrocarbon Analyzer (THA).
- Samples taken from breathing zone: no

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Nominal and actual exposure concentrations were determined. Nominal concentrations were calculated from the test material use rates. Actual concentrations were determined using a Total Hydrocarbon Analyzer for 15 minutes of every hour.

Duration of treatment / exposure:

Four weeks

Frequency of treatment:

6 hours/day, 5 days/week for four consecutive weeks

Remarks:

Doses / Concentrations:
24 mg/m³
Basis:
other: analytical conc. (vapour)

No. of animals per sex per dose:

Twenty

Control animals:

yes

Details on study design:

- Dose selection rationale: Based on survival in a range-finding study

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations included mortality and overt signs of toxicity.

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: Prior to exposure and weekly during exposure

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Study termination
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Study termination
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 2 were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see table 3)

Other examinations:

The heart, lung and trachea, liver, kidneys, brain, spleen, adrenals, thyroid/parathyroid, pituitary, testes and ovaries were weighed.

Statistics:

All continuous data was analyzed using an analysis of variance and Bartlett's test with group comparisons made using an appropriate t-test. Unequal data and data with heterogeneous variances were compared using nonparametric methods using rank transformed data as described by Conover andIman.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Dose descriptor:

NOAEC

Effect level:

>= 24 mg/m³ air (analytical)

Sex:

male/female

Basis for effect level:

other: No treatment-related effects observed.

Critical effects observed:

not specified

There were no treatment-related effects on clinical condition, growth rate, organ or organ body weight ratios or on any of the haematological or clinical chemistry determinations.

Furthermore, there were no treatment-related microscopic changes observed in any of the organs examined.

Conclusions:

There were no treatment-related effects observed at the only concentration tested (mg/m3).

Executive summary:

In a subacute inhalation toxicity study, hydrodesulfurised kerosine (CAS number 64742-81-0) was administered to 20 Sprague-Dawley rats/sex/concentration by dynamic whole body exposure at a concentration of 24 mg/m³(0.024 mg/L) for 6 hours per day, 5 days/week for 4 weeks.

 

There were no compound related effects in mortality, clinical signs, body weight, haematology, clinical chemistry, organ weights, or gross and histologic pathology. Therefore, the NOAEC is greater than or equal to 24 mg/m³. This was the highest dose tested. The test material is not classified according to EU criteria based on no upper limit for the NOAEC.

 

This study received a Klimisch score of 1 and is rated as reliable without restriction because it was carried out in a method similar/equivalent to OECD TG 412.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

yes

Remarks:

Only one dose tested

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Kerosine (petroleum), hydrodesulfurized

EC Number:

265-184-9

EC Name:

Kerosine (petroleum), hydrodesulfurized

Cas Number:

64742-81-0

IUPAC Name:

Kerosine (petroleum), hydrodesulfurized

Constituent 2

Reference substance name:

Hydrodesulfurised kerosine

IUPAC Name:

Hydrodesulfurised kerosine

Test material form:

other: low viscosity liquid hydrocarbon

Details on test material:

- Name of test material (as cited in study report): Hydrodesulfurised kerosine (petroleum), CAS No. 64742-81-0
- Substance type: Kerosine
- Lot/batch No.: API #81-07

Test animals

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., Portage, Michigan
- Age at study initiation: Approximately 6 weeks old
- Weight at study initiation: Males: 126 to 191 grams; Females: 111 to 161 grams
- Fasting period before study: No
- Housing: Each group was maintained in a 1 m3 exposure chamber made of glass and stainless steel. Ten rats were held per cage batteries which were arranged in two tiers of two batteries within each exposure chamber.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 26
- Humidity (%): 20 to 60%

IN-LIFE DATES: From: 1985-01-24 To: 1985-02-22

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposure chamber
- Method of holding animals in test chamber: In cages
- Source and rate of air: HVAC system separate from the general laboratory system
- System of generating particulates/aerosols: Spraying Systems atomizer (No. 64 SS air nozzle, No. 1650 SS liquid nozzle, 1/4 J SS body)
- Air flow rate: 200-240 L/min


TEST ATMOSPHERE
- Brief description of analytical method used: Exposure concentration was determined with a Scott Model 216 Total Hydrocarbon Analyzer (THA).
- Samples taken from breathing zone: no

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Nominal and actual exposure concentrations were determined. Nominal concentrations were calculated from the test material use rates. Actual concentrations were determined using a Total Hydrocarbon Analyzer for 15 minutes of every hour.

Duration of treatment / exposure:

Four weeks

Frequency of treatment:

6 hours/day, 5 days/week for four consecutive weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
24 mg/m³
Basis:
other: analytical conc. (vapour)

No. of animals per sex per dose:

Twenty

Control animals:

yes

Details on study design:

- Dose selection rationale: Based on survival in a range-finding study

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations included mortality and overt signs of toxicity.

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: Prior to exposure and weekly during exposure

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Study termination
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Study termination
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 2 were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see table 3)

Other examinations:

The heart, lung and trachea, liver, kidneys, brain, spleen, adrenals, thyroid/parathyroid, pituitary, testes and ovaries were weighed.

Statistics:

All continuous data was analyzed using an analysis of variance and Bartlett's test with group comparisons made using an appropriate t-test. Unequal data and data with heterogeneous variances were compared using nonparametric methods using rank transformed data as described by Conover andIman.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEC

Effect level:

>= 24 mg/m³ air (analytical)

Sex:

male/female

Basis for effect level:

other: No treatment-related effects observed.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

There were no treatment-related effects on clinical condition, growth rate, organ or organ body weight ratios or on any of the haematological or clinical chemistry determinations.

Furthermore, there were no treatment-related microscopic changes observed in any of the organs examined.

Applicant's summary and conclusion

Conclusions:

There were no treatment-related effects observed at the only concentration tested (mg/m3).

Executive summary:

In a subacute inhalation toxicity study, hydrodesulfurised kerosine (CAS number 64742-81-0) was administered to 20 Sprague-Dawley rats/sex/concentration by dynamic whole body exposure at a concentration of 24 mg/m³(0.024 mg/L) for 6 hours per day, 5 days/week for 4 weeks.

 

There were no compound related effects in mortality, clinical signs, body weight, haematology, clinical chemistry, organ weights, or gross and histologic pathology. Therefore, the NOAEC is greater than or equal to 24 mg/m³. This was the highest dose tested. The test material is not classified according to EU criteria based on no upper limit for the NOAEC.

 

This study received a Klimisch score of 1 and is rated as reliable without restriction because it was carried out in a method similar/equivalent to OECD TG 412.