Chlorosulphuric acid

Endpoint summary

Description of key information

Acute oral toxicity: 

The acute oral toxicity study need not be conducted because the substance is classified as corrosive to the skin. The experimental pH of test chemical is <1. Hence this endpoint is considered for waiver.

Acute Inhalation Toxicity:

The acute inhalation toxicity dose (LC50) was considered based on different studies conducted on rats and mice for the test chemical. The LC50 value is 38.5 mg/m3(0.0385 mg/L). The study concluded that LC50 is <0.05 mg/L, for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 1” for acute inhalation toxicity.

Acute Dermal toxicity:

The acute dermal toxicity study need not be conducted because the substance is classified as corrosive to the skin and it is a strong acid (pH<=2.0). The experimental pH of test chemical is <1. Hence this endpoint is considered for waiver.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Data waiving:

other justification

Justification for data waiving:

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

Justification for type of information:

Oral poisoning is hardly conceivable because the local effects probably do not allow swallowing. However, even the intake of minor amounts into the mouth can rapidly become life threatening. Serious local chemical burns (danger of suffocation due to swelling of the voice box, damage to the blood vessels, danger of perforation) and acute reactions to the heart/circulatory system (shock) are to be expected as a consequence of the corrosive effects.

Endpoint conclusion

Quality of whole database:

Waiver

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:

data from handbook or collection of data

Justification for type of information:

Data is from authoritative database.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute Inhalation toxicity of the given test chemical in rat.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

38.5 mg/m3

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

- Frequency of observations and weighing: The animals were observed for clinical signs and mortality.

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LC50

Effect level:

38.5 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50% mortality was observed.

Mortality:

50% mortality was observed.

Clinical signs:

other: Increased relative liver weight, pulmonary oedema and marked irritation of the mucous membranes were seen.

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

The acute inhalation toxicity dose LC50 value was considered to be 38.5 mg/m3, when rats were treated with the given test chemical via inhalation route for 4-hour exposure.

Executive summary:

Acute inhalation toxicity study of the given test chemical was conducted in rats at the dose concentration of 38.5 mg/m3 via inhalation route for 4-hour exposure. The animals were observed for clinical signs and mortality. 50% mortality was observed. Increased relative liver weight, pulmonary oedema and marked irritation of the mucous membranes were seen. Therefore, LC50 value was considered to be 38.5 mg/m3, when rats were treated with test chemical via inhalation route for 4-hour exposure.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

38.5 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from authoritative database.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

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

Justification for type of information:

The study need not be conducted because the test substance is a strong acid (pH<=2.0). The experimental pH of test chemical is <1. Hence this endpoint is considered for waiver.

Endpoint conclusion

Quality of whole database:

Waiver

Additional information

Acute oral toxicity: 

The acute oral toxicity study need not be conducted because the substance is classified as corrosive to the skin. The experimental pH of test chemical is <1. Hence this endpoint is considered for waiver.

Acute inhalation toxicity:

In different studies, the given test chemical has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for test chemical. The studies are summarized as below –

1. Acute inhalation toxicity study of the given test chemical was conducted in rats at the dose concentration of 38.5 mg/m3 via inhalation route for 4-hour exposure. The animals were observed for clinical signs and mortality. 50% mortality was observed. Increased relative liver weight, pulmonary oedema and marked irritation of the mucous membranes were seen. Therefore, LC50 value was considered to be 38.5 mg/m3, when rats were treated with test chemical via inhalation route for 4-hour exposure.

2. Acute inhalation toxicity study of the given test chemical was conducted in rats at the dose concentration of 40 mg/m3 via inhalation route for 4-hour exposure. The animals were observed for clinical signs and mortality. 50% mortality was observed. The animals showed strong irritation to the airways, motor disturbance and clonic cramps. Besides lung damage, the section revealed histological determined changes to the liver and kidneys, brain congestion as well as focal bleeding in the heart. Therefore, LC50 value was considered to be 40 mg/m3, when rats were treated with test chemical via inhalation route for 4-hour exposure.

3. Acute inhalation toxicity study of the given test chemical was conducted in mice at the dose concentration range of 25 - 52 mg/m3 via inhalation route for 2-hour exposure. The animals were observed for clinical signs and mortality. 50% mortality was observed. The animals showed strong irritation to the airways, motor disturbance and clonic cramps. Besides lung damage, the section revealed histological determined changes to the liver and kidneys, brain congestion as well as focal bleeding in the heart. Therefore, LC50 value was considered to be 52.5 mg/m3, when mice were treated with test chemical via inhalation route for 2-hour exposure.

All the above studies are contradicted with the following studies –

4. Acute inhalation toxicity study of the given test chemical was conducted in four groups of 10 male and 10 female Crl: CD.BR rats at the dose concentration of 0. 1765, 2758, and 5864 mg/m3 (total analytical) or0, 4100, 3800, and 10,000 mg/m3 (nominal concentrations) via inhalation route by nose-only exposures to liquid aerosols for 4-hour exposure. The given test chemical (Purity-99%; Impurity-0.4% H2SO4 and 0.5% free SO3) was tested in an inhalation chamber under dynamic conditions. The control group was exposed only to dry filtered compressed air.

The animals were weighed just prior to exposure (Day 0), and on days 1, 3, 5, 7, 11, and 14 post-exposure. The animals were observed for signs of intoxication a minimum of twice per hour during the exposure and, with the exception of weekends and Day 14, twice daily during the 2-wk post-exposure period. On weekends, the animals were observed once daily for morbidity and mortality and on day 14 the animals were observed once just prior to necropsy.

At the end of the 2-wk observation period, all surviving animals were anesthetized with sodium pentobarbital (45 mg/kg, ip), exsanguinated from the abdominal aorta, and necropsied.

Continuous data, such as body weight changes from Day 0, were first evaluated for normality and homogeneity of variance by residual plots and then analyzed with a two-way analysis of variance (ANOVA). If a significant (p ≤ 0.05) treatment-group by sex effect was observed, then the treatment-group means were compared to those of the control group using least-square-means (SAS, 1982) and Bonferroni t-test (Miller, 1981). The combined male and female response, as well as the separate male and female responses, were used, when possible, to calculate the LC50s, 95 % confidence limits, and slopes using a log probit regression analysis (Finney, 1971).

Combined male and female mortalities of 0% (0/20), 40% (8/20), 65% (13/20), and 45% (9/20) occurred among animals exposed to concentrations of 0, 1765, 2768, and 5864 mg/m3 , respectively.

Exposure to test chemical produced signs of sensory irritation (bradypnea and apnea) and pulmonary irritation (dyspnea, rales, and gasping) (Alarie, 1973) and mortality during and immediately following the exposure. With the exception of mortality, the severity and incidences of these effects increased with increasing concentration. The persistence of signs of pulmonary irritation after cessation of exposure indicated that CSA produced significant lower airway irritation (Alarie, 1966). The appearance of red-stained nuzzles and red spotting on the drop. Sheets concluded to be expired nasal exudates were indicative of nasal muccsa irritation. Signs of central nervous system depression, (ataxia and prostration) observed during the fourteen-day observation period were judged to be secondary to hypoxia produced by respiratory distress.

The reduction in body weight and body weight gain were more pronounced in males than in females. In the males the effect on body weight paralleled the mortality response data; that is, a greater effect occurred in the 2768 mg/m3 exposed males than in the 5864 mg/m3 exposed males. The female body weight data was consistent with concentration. It was not possible to determine from these data if the body weight effects were secondary to the respiratory distress or a systemic toxic effect.

The organ weight response observed in the males was consistent with the organ weight response observed in feed restricted rats (Scharer, 1977) and was considered a function of the reduced body weights exhibited by the animals in the 1765 and 2768 mg/m3 exposure groups. In the absence of an effect on the absolute fixed brain and gonad weights, these changes were not considered treatment-related.

In females, the absolute fresh liver weight reductions in the 1765 and 5864 mg/m3 groups, without a concurrent effect on relative fresh liver weights, were considered an effect of the reduced body weights. The fixed spleen weight reductions observed in the 2768 mg/m3 exposure group were judged to be unrelated to treatment in the absence of a similar effect in the 5864 mg/m3 group.

No treatment-related effect was observed in necropsy. Therefore, the LC50 value was considered to be >1765 mg/m3, for male and female rats, and male rats separately and calculated to be 4779 mg/m3 for female rats, when Four groups of 10 male and 10 female Crl:CD.BR rats were treated with test chemical via inhalation route by nose-only exposures to liquid aerosols for 4-hour exposure.

5. Acute inhalation toxicity study of the given test chemical was conducted in Groups of five male and five female Crl:CD®(SD)BR rats at the dose concentration of 3400, 2250, 1500, 563, 282, or 70 mg/m3 via inhalation route by vapour for 1-hour exposure.

The animals were observed for 14 days post-exposure. Mortality was observed during the observation period at the three highest dose levels. Mortality was observed over the two-week period in groups exposed to 3400, 2250, or 1500 mg/m3. Delayed mortality was not clearly concentration dependent. One female exposed to 1500 mg/m3 survived. Clinical signs of respiratory irritation seen in the 563 mg/m3 exposure group resolved within 8 hours after exposure. Body weight gain was comparable among groups exposed to 563, 282, or 70 mg/m3. Compound-related gross lesions in animals exposed to 3400, 2250, or 1500 mg/m3 included lung haemorrhage, enlarged livers, pale and small spleens and small thymuses (1500 mg/m3 females). Microscopic examination revealed degenerative and inflammatory changes of the respiratory tract particularly tracheal lesions in all groups exposed to 3400, 2250, or 1500 mg/m3. The test material also produced liver hypertrophy and degenerative changes in spleens and thymuses. Airway obstructions from tracheal lesions were the probable cause of death. There were no compound-related gross or histopatbologic changes detected in animals exposed to 563, 282, or 70 mg/m3. The no-observed-effect concentration for toxicity was 282 mg/m3.

Considering the observations of the above study, the LC10 value was considered to be 926 mg/m3, when Groups of five male and five female Crl:CD®(SD)BR rats were treated with test chemical via inhalation route by vapour for 1-hour exposure.

Thus, based on the above summarised studies on test chemical, maximum studies concluded that the LC50 value is <0.05 mg/L, for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 1” for acute inhalation toxicity.

Acute Dermal toxicity:

The acute dermal toxicity study need not be conducted because the substance is classified as corrosive to the skin and it is a strong acid (pH<=2.0). The experimental pH of test chemical is <1. Hence this endpoint is considered for waiver.

Justification for classification or non-classification

Based on the above studies on test chemical, it can be concluded that LC50 value is <0.05 mg/L, for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “category 1” for acute inhalation toxicity. For acute oral and acute dermal toxicity wavier was added so, not possible to classify.