Barium sulfate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonably well described inhalation study. No guideline is stated. Furthermore, no NOAEC could be derived. Therefore, the study could not be used for risk assessment purposes.

Data source

Reference

Reference Type:

publication

Title:

Die histologischen Veränderungen an der Lunge nach kurzzeitiger Inhalation von Bariumsulfat (Tierversuche)

Author:

Holuša, R. et al.

Year:

1973

Bibliographic source:

Beitr. Silikose-Forsch. (Pneumokon.) 25:1 - 14.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

During a 2-month period, Wistar rats were exposed to 40 mg/m^3 barium sulfate on 5 weekdays for 5 hours per day. During the 2-month inhalation exposure period animals were sacrificed and the lungs and lymph nodes were histologically investigated at a 14 day interval. After the 2-month exposure period a post-inhalation period followed in which the animals were observed for an additional 2 and 4 weeks.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Barium sulfate

EC Number:

231-784-4

EC Name:

Barium sulfate

Cas Number:

7727-43-7

Molecular formula:

BaO4S

IUPAC Name:

barium sulfate

Details on test material:

- Name of test material (as cited in study report): Barium sulphate (BaSO4) (From Merck)
- Particle size distribution: 1-2 µm
No further information on the test material was stated.

Test animals

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

No information on the test animals was given in the publication.

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

other: no data

Remarks on MMAD:

MMAD / GSD: No data

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A box of 6.5 m^3 in which the rats were held. They were exposed following the Klosterkötter and Einbrodt (1965) procedure.
No further information on details on inhalation exposure was stated.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

2 months

Frequency of treatment:

On 5 weekdays for 5 hours per day

Doses / concentrations

Remarks:

Doses / Concentrations:
40 mg/m^3 BaSO4
Basis:
nominal conc.

No. of animals per sex per dose:

84 animals were exposed. How many of each sex was not stated.

Control animals:

not specified

Details on study design:

- Post-exposure observation period: After the inhalation-exposure period, a post-inhalation period of 2 and 4 weeks followed. During this period, the lungs and extrapulmonary lymph nodes were removed and were dyed for histological examination at 2 weeks and 4 weeks.
No further information on study design was stated.

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: No data
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
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: No data
HAEMATOLOGY: No data
CLINICAL CHEMISTRY: No data
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data
No further information on observations and examinations performed and frequency were stated.

Sacrifice and pathology:

The first animals were sacrificed 20 hours after den first exposure of 5 hours. Further animals were killed after every 10th exposure to the test substance. The lungs and extrapulmonary lymph nodes were removed and were dyed for histological examination.
No further information on sacrifice and pathology were stated.

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

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 specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

HISTOPATHOLOGY: non-neoplastic
An initial rapidly progressing cellular reaction of the lung parenchyme was followed by a proliferation of alveolar macrophages and a peculiar modification of bronchiolar epithel. These epithelial changes regress slowly during the experiments without causing lung damage.

Effect levels

Dose descriptor:

conc. level:

Effect level:

40 mg/m³ air (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: see 'Remark'

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

An initial rapidly progressing cellular reaction of the lung parenchyme was followed by a proliferation of alveolar macrophages and a peculiar modification of bronchiolar epithel. These epithelial changes regress slowly during the experiments without causing lung damage.