Sulphuric acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published investigative non-guideline, non-GLP study.

Data source

Reference

Reference Type:

publication

Title:

Clearance Of Sulfuric Acid-Introduced 35S From The Respiratory Tracts Of Rats, Guinea Pigs And Dogs Following Inhalation Or Instillation

Author:

Dahl AR, Felicetti SA & Muggenburg BA

Year:

1983

Bibliographic source:

Fundamental & Applied Toxicology 3 (4) 293-297

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Deviations:

not applicable

Principles of method if other than guideline:

The study was performed to elucidate the toxicokinetics of the sulphate anion following the inhalation exposure of various species to aerosols of sulphuric acid.

GLP compliance:

no

Remarks:

: older, published study

Test material

Test material information

Constituent 1

Reference substance name:

Sulphuric acid

EC Number:

231-639-5

EC Name:

Sulphuric acid

Cas Number:

7664-93-9

Molecular formula:

H2O4S

IUPAC Name:

sulfuric acid

Details on test material:

35-S radiolabelled sulphuric acid

Radiolabelling:

yes

Remarks:

35S-sulphuric acid

Test animals

Species:

other: Rat, guinea pig and dog

Strain:

other: F344, Hartley, beagle

Sex:

male

Administration / exposure

Route of administration:

other: inhalation and instillation

Vehicle:

water

Duration and frequency of treatment / exposure:

See below for methodological details

Doses / concentrations

Remarks:

Doses / Concentrations:
See below for methodological details

No. of animals per sex per dose / concentration:

See below for methodological details

Control animals:

no

Results and discussion

Preliminary studies:

No information.

Toxicokinetic / pharmacokinetic studies

Details on excretion:

Clearance into the blood and gastrointestinal tract was measured along with determination of 35S remaining at the site of administration at sacrifice. Different rates of clearance from different sites within the dog lung were indicated with rates of clearance increasing with decreasing airway diameter. Half-times of clearance from all sites in the lung and for all species were from 2–9 min. There appeared to be some species differences, with clearance for dogs being slower than for guinea pigs, which was slower than for rats. Upper respiratory tract clearance was much slower than for lung and may not have been primarily by way of the blood.

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

Not applicable. The study was performed to elucidate the fate of the sulphate anion.

Any other information on results incl. tables

A considerable variability in clearance rates from blood and lungs was noted in rats and dogs. The half-time for 50% clearance from the lungs of all animals was in the range of 2-9 minutes.  The rate of clearance for dogs was slower than guinea-pigs, which was slower than for rats.  The clearance rates from the upper respiratory tract, trachea, and larynx were much slower than for lung for all three species of animals.  The authors conclude that the half time for the clearance of sulphuric-acid in dogs, guinea-pigs, and rats is shorter than values reported in the literature involving isolated perfused lungs; smaller lung airways may clear faster than larger airways.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Sulphate is rapidly absorbed from the lungs following inhalation exposure to sulphuric acid.

Executive summary:

The clearance of 35S-radiolabeled sulphuric acid aerosols from the respiratory tract was studied in rats, guinea pigs, and dogs exposed nose-only to l-20 mg/m³ (MMAD 0.4-l .2 µm) for 30 seconds, and in rats and guinea pigs following intranasal installation (Dahl et al. 1983). The results indicated that the sulphur from sulphuric acid is rapidly cleared from the lungs into the blood following inhalation exposure.  The lung clearance half-times were 170,230, and 261 seconds in rats, guinea pigs, and dogs, respectively.  Very little sulphate from the sulphuric acid placed in the nose was absorbed into the rest of the body.  Five minutes after treatment, 97.1% and 96.8% of the dose remained in the nose of rats and guinea pigs, respectively.  To further study absorption of sulphuric acid by the respiratory tract of dogs, 35S-labeled sulphuric acid was instilled in one dog l-2 cm past the nares, in a second generation bronchus of another dog, and in a seventh generation bronchus of a third dog.  Clearance from the nasal region was insignificant.  Clearance half-time from the second generation bronchus was 200 seconds; from the seventh generation bronchus it was 110 seconds.