Distillates (petroleum), heavy straight-run

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was well reported and conducted to OECD guidelines with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

64741-44-2

Cas Number:

64741-44-2

IUPAC Name:

64741-44-2

Constituent 2

Reference substance name:

Straight run middle distillate

IUPAC Name:

Straight run middle distillate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): MRD-91-960
Sponsors's code 91119

- Substance type: petroleum UVCB substance
- Physical state: amber liquid
- Analytical purity: 100%

- Storage condition of test material: room temperature

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., Kingston, NY
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 255-401 g

- Housing: acclimation - paired by sex for approximately one week, then housed individually thereafter
- study individually housed during and after exposure
- Diet (e.g. ad libitum): certified Purina Rodent Laboratory Chow 5002 (pellets), ad libitum during non-exposure periods, without food while in chamber
- Water: ad libitum during non exposure periods, without water while in chamber
- Acclimation period: approx. 27 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-73 degrees F
- Humidity (%): 48-81% RH
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose-only exposure chamber with 12 exposure ports, ten used for animal exposure, 2 for sampling
- Exposure chamber volume: 54 liters
- Method of holding animals in test chamber: each animal was placed in an acrylic nose-only exposure tube.

- System of generating particulates/aerosols: test material was delivered via a laboratory piston pump to an air atomizer. Compressed air was supplied to the atomizer at approximately 10 psi backpressure, causing the resultant aerosol droplets to be expelled into the chamber. A glass diffuser removed larger particles before the aerosol entered the exposure chamber.

- Method of particle size determination: conducted twice during the exposure using a Sierra model 210 cascade impactor. Glass fibre filters were used to collect sample on each of 8 stages with decreasing cutoff for particle size.
Chamber homogeneity was checked for each of the 12 ports during trials for the study.
Chamber static pressure was maintained slighlty negative to the exernal room pressure.

TEST ATMOSPHERE
- Brief description of analytical method used: exposure concentrations were determined on a nominal and actual basis.
nominal: calculated by weighing the flask containing test material before and after exposure and dividing the net loss by the total volume of air passing through the chamber
actual: determined gravimetrically by drawing a known volume of air through a pre-weighed glass fibre filter. At least one such sample was taken during each hour of exposure.

TEST ATMOSPHERE (if not tabulated)
mean exposure concentration: 2.53 mg/l (actual); 3.14 mg/l (nominal)
homogeneity: coefficient of variation for the 12 ports 3.3% indicating a high degree of homogeniety
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter): 2.4 microns
% aerosol % aerosol % aerosol

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric

Duration of exposure:

4 h

Concentrations:

Limit test at 2.53 mg/L (measured)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed every 15 minutes for the first hour and then at hourly intervals during the exposure period. Detailed individual observations on all animals were recorded pre-exposure, immediately post-exposure and then daily for fourteen days. Bodyweights were recorded for all animals pre-exposure (day 0) and on days 7 and 14
- Necropsy of survivors performed: yes

Statistics:

Means and standard deviations were calculated for relevant exposure and animal data

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.53 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No animals died during the study

Clinical signs:

other: See Other findings below

Body weight:

All animals gained weight throughout the study, weight gains were slightly lower for the first week than the second week in both sexes.

Gross pathology:

5 animals had slightly discoloured lungs (mottled in 2 rats and single or small numbers of dark red foci in 3 rats. This was probably related to exposure.
Other minor abnormalities included single incidences of enlarged kidneys, discoloured mandibular lymph nodes and alopecia on the extremities.
4 animals had no macroscopic abnormalities.

Other findings:

A few animals exhibited laboured breathing starting approximately thirty minutes into the exposure. Incidences of laboured breathing increased as the exposure progressed, and during the last two hours all the animals exhibited laboured breathing. Individual animals also displayed decreased activity, a closed eye, clear ocular discharge, brown ano-genital staining of the fur, and brown material on the fur of the dorsal lumbar area.

Most animals recovered by the day following exposure (although one male exhibited laboured breathing). Other abnormalities that were
observed on Day 1 included ungroomed fur, dry red material around the left eye, brown or yellow ano-genital staining, and brown material on the fur of the dorsal lumbar area. All the animals appeared normal by Day 3 post-exposure.

One animal developed alopecia on the head from Day 5 through Day 13 and exfoliation on the dorsal cervical area from Day 5 through Day 9. Another animal had alopecia of the extremities from Day 7 through 14 post-exposure. There were also single scattered incidences of scabs on the extremities and dorsal cervical area. These observations were considered incidental and probably not related to exposure to the test material.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based upon tne results of this study, the four hour LC50 is greater than 2.53 mg/1.

Executive summary:

In a key acute inhalation toxicity study, the test material (CAS no. 64741-44-2) was administered to Sprague-Dawley rats (5/sex/dose) via inhalation (in air; nose only) at a concentration of 2.53 mg/L for a period of 4 hours. 

Post-exposure animals were observed every 15 minutes for the first hour, and then at hourly intervals during the exposure period. Detailed individual observations on all animals were recorded pre-exposure, immediately post-exposure and then daily for fourteen days. Bodyweights were recorded for all animals pre-exposure (day 0) and on days 7 and 14 of the study period. Necroscopy was conducted for all surviving animals at termination and means and standard deviations calculated.

A few animals exhibited laboured breathing starting approximately thirty minutes into the exposure. Incidences of laboured breathing increased as the exposure progressed, and during the last two hours all animals exhibited laboured breathing. Individual animals also displayed decreased activity, a closed eye, clear ocular discharge, brown ano-genital staining of the fur, and brown material on the fur of the dorsal lumbar area. Most animals were observed to have recovered by Day 1 post-exposure (although one male exhibited laboured breathing). Other abnormalities observed on Day 1 included ungroomed fur, dry red material around the left eye, brown or yellow ano-genital staining, and brown material on the fur of the dorsal lumbar area. All animals appeared normal by Day 3 post-exposure. One animal developed alopecia on the head from Day 5 through Day 13 and exfoliation on the dorsal cervical area from Day 5 through Day 9. Another animal had alopecia of the extremities from Day 7 through 14 post-exposure. Also observed, were single scattered incidences of scabs on the extremities and dorsal cervical area. These observations were considered incidental and probably not related to exposure to the test material. All animals gained weight throughout the study; weight gains were slightly lower for the first week than the second week in both sexes.

There were no deaths during the study. Necroscopy revealed that 5 animals had slightly discoloured lungs (mottled in 2 rats and single or small numbers of dark red foci in 3 rats). This was probably related to exposure. Other minor abnormalities included single incidences of enlarged kidneys, discoloured mandibular lymph nodes and alopecia on the extremities. 4 animals had no macroscopic abnormalities.

Based upon the results of this study, the four hour acute inhalation LC₅₀ for the test material was determined to be greater than 2.53 mg/L.