Sulphuric acid

Endpoint summary

Description of key information

A single acute oral toxicity study is available; this is broadly comparable to OECD Guideline 401.  No acute dermal toxicity studies are available.  A large number of non-standard acute inhalation studies are available; studies were performed in various species and using various exposure times.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-guideline study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Surviving animals were observed for 21 days and not the guideline required 14 days.

Principles of method if other than guideline:

The study protocol is broadly compliant with OECD 403, with the exception that exposure was for 1, 2, 4, or 8 hours and that the surviving animals were observed for 21 rather than 14 days.

GLP compliance:

no

Remarks:

: study pre-dates GLP.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: aerosols of sulphuric acid were generated by mixing sulphur trioxide vapour with humid air.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

>= 1 - <= 8 h

Concentrations:

250, 500, 750 and 1000 mg/m3 air; 0.25, 0.5 and 1 mg/l

No. of animals per sex per dose:

Four/sex/dose

Control animals:

no

Sex:

male/female

Dose descriptor:

LC50

Effect level:

375 mg/m³ air

A relationship between increased mortality and higher test material concentrations (c) and also with exposure time (t) was observed in both species tested, but rat mortality increased more rapidly than mouse mortality for both variables.  Mortality was not proportional to ct; and the LC50 values are dependent on the exposure time.  The LC50 (4h) was ~375 mg/m3, while the LC50 (8h) was ~425 mg/m3.  These values are based on total deaths occurring in the 21 days after exposure.  It is suggested that the fibrosis occurring in the rat may cause malfunction of the epiglottis and subsequently result in foreign body aspiration and subsequent pneumonia. 

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Although the LC50 values from the inhalation toxicity study theoretically trigger Classification with (R23) 'Toxic by inhalation', classification is not proposed. The effects of sulphuric acid following inhalation are entirely due to local irritation of the respiratory tract: there is no evidence for the systemic toxicity of sulphuric acid in any study as effects are limited to the site of contact. Classification for acute inhalation toxicity is not considered to be appropriate.

Executive summary:

Groups of F344 rats (5/sex) were exposed (whole body) to aerosols of sulphuric acid (generated by combining sulphur trioxide and humid air) at a number of concentrations and exposure times between 1-8 hours. Histopathology of the respiratory tract revealed ulceration of the nasal turbinates, trachea and larynx immediately following exposure; laryngeal fibrosis and inhalation pneumonia were seen in decedents at 1 -2 weeks following exposure. A clear relationship between mortality and Ct is not apparent from the results of this study; the 4 -hour LC50 value (relevant for classification purposes) was found to be approximately 375 mg/m3 (0.375 mg/l).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

375 mg/m³ air

Quality of whole database:

Klimisch score = 2. Study comparable to current guidelines; pre-dates GLP.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

 

The single available acute oral toxicity study (Smyth et al, 1969) performed with sulphuric acid reports an LD50 value of 2140 (1540 -2990) mg/kg bw. The study is reported in summary form only but the protocol design is comparable to OECD 401. The results of this study indicate that sulphuric acid is of low acute systemic toxicity when administered by gastric intubation. However it should be noted that the route of administration used in this study eliminates the potential for local corrosive effects of the test material on the upper gastrointestinal tract (mouth, pharynx and oesophagus). Following accidental/intentional oral ingestion of sulphuric acid by humans, the local effects on the upper gastrointestinal tract are likely to dominate the clinical presentation and the potential for systemic toxicity is likely to be low. Further testing of sulphuric acid for acute oral toxicity in animals (i.e. in a guideline- and GLP-compliant study) is not proposed for acute oral toxicity and for reasons of animal welfare, due to the corrosivity of the substance.

 

Acute dermal toxicity

 

No data on acute dermal toxicity in animals are available. Although this is a potential route of exposure for workers, testing is not justified for scientific reasons and on animal welfare grounds. The effects of acute dermal exposure to sulphuric acid on animals can be readily predicted, and the data from human exposure are sufficient to characterise the effects.

 

Acute inhalation toxicity

 

A number of acute inhalation toxicity studies have been performed with sulphuric acid, using various species and exposure times.

 

In all tested species (rats, mice, rabbits and guinea pigs) the concentration of acid aerosol, the length of exposure and particle size are important factors in determining lethality by inhalation.  Among the different species tested, the guinea pig appears to be the most sensitive to the acute inhalation toxicity of sulphuric acid mist/aerosols.  In the guinea pig, the apparent LC50 for an 8 hour-exposure period to sulphuric acid mist/aerosol with a particle size of approximately 1 um ranges from 0.018-0.050 mg/l depending on the age of the animals, with younger guinea pigs apparently more sensitive to than older animals. In the more reliable studies performed in other species, LC50 values vary with exposure duration and are in the range 0.375-0.425 mg/l in the rat, 0.600-0.850 mg/l in the mouse and 1.47-1.61 mg/l in the rabbit.  The sensitivity of the guinea pig may be caused by its tendency to bronchoconstriction and laryngeal spasm compared with the other tested species.  The main macroscopic and or microscopic alterations observed in respiratory tract following acute inhalation exposure were haemorrhage, oedema, atelectasis and thickening of the alveolar wall in the guinea pig lung; haemorrhage and oedema of the lungs, ulceration of the nasal turbinates, trachea and larynx in rats and mice. These lesions are directly related to the corrosive/irritant effects of sulphuric acid and there is no indication of systemic toxicity following acute inhalation exposure.

Justification for selection of acute toxicity – oral endpoint
A waiver is presented for this endpoint

Justification for selection of acute toxicity – inhalation endpoint
Guideline-comparable study

Justification for classification or non-classification

Based on the results of the acute oral toxicity study, no classification for acute oral toxicity is proposed according to current EU criteria.

No classification is proposed for acute dermal toxicity in the absence of an appropriate study; the acute dermal toxicity of sulphuric acid is dominated by local corrosivity and irritancy and is therefore sufficiently addressed by the current classification of the substance as corrosive.

Although the LC50 values from the various inhalation toxicity studies performed with sulphuric acid theoretically trigger classification for acute inhalation toxicity, classification is not proposed. The effects of sulphuric acid following inhalation are entirely due to local irritation/corrosivity of the respiratory tract: there is no evidence for the systemic toxicity of sulphuric acid in any study as effects are limited to the site of contact. As the substance already carries classification for its corrosive effects, classification for acute inhalation toxicity is not considered to be appropriate.