Pentane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-10-09 to 1997-02-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study is classified as reliable without restriction because it is in compliance with OECD principles of GLP and E.U. Council Decision on GLP, as well as the European Community Dangerous Substance Directive (67/548/EEC), Methods of Determination of Toxicity, Annex VIII.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Deviations:

yes

Remarks:

Protocol deviations were noted and were not expected to affect the overall study results.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EC, Annex VIII, Sub-chronic inhalation toxicity, 1988

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pentane

EC Number:

203-692-4

EC Name:

Pentane

Cas Number:

109-66-0

Molecular formula:

C5H12

IUPAC Name:

pentane

Details on test material:

- Name of test material (as cited in study report): n-pentane
- Substance type: C5 alphatics
- Physical state: liquid
- Analytical purity: 97.4%
- Expiration date of the lot/batch: 5 years from date of received (i.e., June, 2001 and December, 2001)
- Storage condition of test material: room temperature
- Other: The testing laboratory was stated to have analyzed for stability, identity, strength, purity, and composition of the test material, but the information was not provided in the study report.

Test animals

Species:

rat

Strain:

other: Crl: CDBR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Kignstone Facility, Stone Ridge, New York
- Age at study initiation: 7 to 8 weeks old
- Weight at study initiation: males: 229.8 to 255.8 grams; females: 184.8 to 213.4 grams
- Housing: individually housed in suspended stainless steel and wire mesh cages with absorbent paper below during study period and individually housed in 1.5 cubic meter statinless steel and glass whole body inhalation chambers during exposure
- Diet (e.g. ad libitum): ad libitum during nonexposure periods
- Water (e.g. ad libitum): ad libitum during nonexposure periods
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 64 to 72 °F
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours light

IN-LIFE DATES: From: 1996-11-18 To:1997-02-21

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: not reported

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: vapor generator into a whole body inhalation chamber (1.5 cubic meter)
- Source and rate of air: air flow rate was 300 litres per minute
- Temperature, humidity, pressure in air chamber: 66 to 72°F, 40 to 70% relative humidity, under slightly negative pressure to the room
- Air flow rate: 300 litres per minute

TEST ATMOSPHERE
- Brief description of analytical method used: Hourly measurements from five different locations in the chamber were made by on-line gas chromatography.
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

analytical concentrations for the 5000; 10,000; and 20,000 mg/m3 concentrations were as follows: 5097±79; 10,203±151; and 20,483±734 mg/m3

Duration of treatment / exposure:

6 hours a day plus chamber equilibrium time (theoretically=23 minutes)

Frequency of treatment:

5 days a week for 13 weeks; males had three additional treatments during the 14th week and females had four additional treatments

Doses / concentrations

Remarks:

Doses / Concentrations:
5097±79, 10,203±151, and 20,483±734 mg/m3
Basis:
analytical conc.

No. of animals per sex per dose:

10 animals/sex/dose

Control animals:

yes

Details on study design:

- Dose selection rationale: Doses were selected based on a range finding study with concentrations up to 21,000 mg/m3 without any noted effects.

Positive control:

not reported

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily prior to exposure, once a day on nonexposure days, during the first and sixth hour of exposure


BODY WEIGHT: Yes
- Time schedule for examinations: prior to study initiation, weekly thereafter, and at study termination


FOOD CONSUMPTION:
- Food consumption for each animal determined: Yes, specified in grams


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 data


WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: prior to study initiation and during the final week of the study
- Dose groups that were examined: all dose groups


HAEMATOLOGY: Yes
- Time schedule for collection of blood: at terminal sacrifice
- Anaesthetic used for blood collection: Yes, IP injection of sodium pentobarbital
- Animals fasted: Yes
- How many animals: all 40 animals
- Parameters checked in table were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at terminal sacrifice
- Animals fasted: Yes
- How many animals:all 40 animals
- Parameters checked in table were examined.


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see table)

Other examinations:

The following organs were weighed: adrenals, brain, epididymis, kidneys, liver, lungs plus trachea, prostate, seminal vesicles (with coagultion gland), spleen, testes or ovaries, thymus, and uterus.

Statistics:

Bartlett's test for equal variance (p<0.01); parametric procedures included a one-way ANOVA with F distribution followed by Dunnett's test and a standard regression analysis for linear response (p<0.05 and p<0.01); nonparametric proceduresincluded the Kruskal-Wallis test followed by Dunn's summed rank test and Jonckheere's test for monotonic trends (p<0.05 and p<0.01)

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):

no effects observed

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

no effects observed

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

Details on results:

not reported

Effect levels

Key result

Dose descriptor:

NOAEC

Effect level:

20 000 mg/m³ air (nominal)

Sex:

male/female

Basis for effect level:

other: lack of any effects

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

There were sporadic statistically significant results. However, none of the results were considered clinically significant or related to treatment.

Applicant's summary and conclusion

Conclusions:

Inhalation exposure to n-pentane at concentrations ≤20,000 mg/m3 did not cause any observable adverse effects in male or female rats.

Executive summary:

In a subchronic inhalation toxicity study, n-pentane was administered to 10 rats/sex/concentration by whole body exposure at analytical concentrations of 5097±79; 10,203±151; or 20,483±734 mg/m3 6 hours a day, 5 days a week for 13 weeks. Animals were sacrificed in the fourteenth week after 3 (males) or 4 (females) exposures. There were no treatment-related effects observed for clinical signs, body weight, food consumption, hematology, clinical chemistry, ophthalmology, gross pathology, organ weights, or histopathology. This study is classified as reliable without restrictions because it is in compliance with OECD principles of GLP and E.U. Council Decision on GLP, as well as the European Community Dangerous Substance Directive (67/548/EEC), Methods of Determination of Toxicity, Annex VIII. In addition the study was performed according to OECD 413 guidelines.