Reaction mass of 4-hydroxybenzene-1,3-disulphonic acid and 4-hydroxybenzenesulphonic acid and sulphuric acid and water

Endpoint summary

Description of key information

LD50 oral = 1410 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

Aug 25 - Sept 27, 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well described GLP compliant study conducted to recognized international test guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG colony
- Age at study initiation: males - 7 weeks, females - 8 weeks
- Weight at study initiation: males - 194-202 g; females 181-196 g
- Fasting period before study: overnight
- Housing: in groups of 5
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): not provided
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: August 25 To: September 27, 1988

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

1250, 1600 and 2000 mg/kg for females; 2000 mg/kg for males

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 28 days
- Frequency of observations and weighing: observations daily starting on day of exposure; body weight weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

Probit analysis

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 410 mg/kg bw

Based on:

act. ingr.

Mortality:

2 of 5 males at 2000 mg/kg; 2 of 5, 3 of 5, and 4 of 5 females died at 1250, 1600 and 2000 mg/kg, respectively. Death almost always occurred within one day of dosing.

Clinical signs:

other: Main clinical signs were hypoactivity, hunched posture, irregular breathing in all animals at all doses on day 1 and then reversible within 3 days for males at 2000 mg/kg and within 2 days for females at 1250 mg/kg. For females at 1600 and 2000 mg/kg the

Gross pathology:

Red discolouration of the GI tract filled with blood; white discouloration of the mucosa of the stomach and intestine; pale adrenals, stomach haemorrhages and abdomen filled with flied (in animals that died spontaneously). No sex specific differences.

Other findings:

NOAEL = 1250 mg/kg bw

Mortality: number of deaths at each dose: 2/5, 3/5 and 4/5 at 1250, 1600 and 2000 mg/kg for females, and 2/5 at 2000 mg/kg for males.

Time of death was Day 1 for all but one animal at 1600 mg/kg that died on day 13.

Clinical signs: hypoactivity, hunched posture, irregular breathing were observed in all animals from all dose groups on day 1 and was reversible within 3 days for males at 2000 mg/kg. For females, the above symptoms plus abnormal gait, ptosis and piloerection were seen in all animals at 1600 and 2000 mg/kg and were not reversible.

Necropsy findings: Red discolouration of the GI tract filled with blood, white discolouration of the mucosa of the stomach and intestine, pale adrenals, growing together of the stomach and nearby organs, stomach haemorrhages and abdomen filled with fluid (in animals that died).

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The test substance has an acute oral LD50 of 1410 mg/kg bw. The NOAEL is 1250 mg/kg/bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 410 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1962

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not a guideline study; some details on methodology, but concentration of test substance that the animals were exposed to is not reported. Indicated only as "saturated air".

Principles of method if other than guideline:

Exposure to concentrated vapour is continued for time periods in a logarithmic series with a ratio of the two extending from 15 minutes to 8 hours until the inhalation period killing about half the number of rats within 14 days of observation is defined.

GLP compliance:

no

Test type:

fixed concentration procedure

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

For exposures of 2, 5 or 10 minutes, a static technique was used by saturating the air with 50-100 g of test substance for 24 hours in a closed chamber. For exposures beyond 10 minutes a flowstream of saturated vapour was used.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

>= 0.25 - <= 8 h

Concentrations:

Not reported. Air was saturated with 50-100 g of test substance

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not reported
- Necropsy of survivors performed: no
- Other examinations performed: none reported

Sex:

not specified

Dose descriptor:

LC50

Effect level:

>= 50 - ca. 100 other: mg

Based on:

test mat.

Exp. duration:

8 h

Mortality:

3 of 6 animals died within 14 days after an 8 hour exposure. No deaths were reported for shorter duration exposures (i.e, 15, 30, 45 minutes; and 1, 2 and 4 hours).

Interpretation of results:

harmful

Remarks:

Migrated information under saturated air conditions Criteria used for interpretation of results: expert judgment

Conclusions:

3 of 6 animals died within the 14-day observation period following an 8 hour exposure to a saturated air vapour of test substance

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

50 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1968-04-23

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to the OECD Guideline, Pre GLP study. Not a full study report.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

6 animals were used for study instead of 10 (5 male and 5 female animals)

Principles of method if other than guideline:

None

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not available
- Age at study initiation: Not available
- Weight at study initiation: 2703 grams (Abraded skin), 2730 grams (Intact skin)
- Fasting period before study: Not available
- Housing: Not available
- Diet (e.g. ad libitum): Not available
- Water (e.g. ad libitum): Not available
- Acclimation period: Not available


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not available
- Humidity (%): Not available
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): Not available


IN-LIFE DATES: 1968-04-23

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: Not available
- % coverage: Not available
- Type of wrap if used: Not available


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not available
- Time after start of exposure: Not available


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg bw
- Concentration (if solution): Not available
- Constant volume or concentration used: yes
- For solids, paste formed: Not available


VEHICLE
- Amount(s) applied (volume or weight with unit): Not available
- Concentration (if solution): Not available
- Lot/batch no. (if required): Not available
- Purity: Not available

Duration of exposure:

Not available

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Total 6 animals were taken for the study. Sex was not mentioned.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Not available
- Necropsy of survivors performed: Not available
- Other examinations performed: Clinical signs, body weight

Statistics:

None

Preliminary study:

None

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

0/3 (Abraded skin), 0/3 (Intact skin)

Clinical signs:

other: Sodium Cumene Suphonate elicited moderate primary irritation on the test sites.

Gross pathology:

Not available

Other findings:

- Organ weights: None
- Histopathology: None
- Potential target organs: None
- Other observations: None

None

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The LD50 > 2000 mg/kg bw and test substance is considered practically non toxic.

Executive summary:

The LD50 was >2000 mg/kg bw. This test substance is practically non toxic.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The key study is a 1988 GLP guideline study of male and female rats exposed by oral gavage to toluene-4-sulphonic acid (CAS No, 104-15-4). The LD50 value was 1410 mg/kg bw. Given the predominance of deaths occurring within the day of exposure and the necropsy findings, it is likely that the deaths were a result of the acidity / corrosivity of the test substance. The internal examination findings (e.g., GI tract filled with blood; stomach haemorrhages and abdomen filled with fluid) suggest a secondary effect (i.e., corrosion) rather than a chemical toxicity.

In addition to the key study, there are 2 supporting acute oral studies a 1977 test of xylenesulphonic acid (CAS No. 25321-41-9) and a 1962 published study of benzenesulphonic acid (CAS No. 98-11-3). Both of these studies, as well as two additional published studies support the LD50 value of 1410 mg/kg bw reported in the key study.

There are not data for dermal acute toxicity. The aromatic sulphonic acids are corrosive and therefore with regard to animal welfare, dermal studies are not recommended. There are however acute dermal toxcity studies for the closely related hyrotropes that are the salt form of the sulphonic acids. The LD50 for the salts is >2000 mg/kg bw.

A single acute inhalation study concluded the acids are harmful at saturated air conditions as 3 of 6 animals died. A concentration was not reported.

Justification for selection of acute toxicity – oral endpoint
Between all analogous substances of the multiconstituent, the monosulphonated acid is the most conservative one. The study on toluene sulphonic acid has been chosen because the better describes and conducted following official guideline

Justification for classification or non-classification

Since it is not possible to directly assess the toxicity of sulphonic acids due to the corrosion/irritation effects, read-across from the hydrotopes resdults could be taken into account.

The studies with the salts (hydrotropes) provide valid read-across for the acids. The specific cation is not expected to have an appreciable effect on fate, ecotoxicity or mammalian toxicity and therefore the dataset for the entire hydrotropes category can be applied broadly. 

The aromatic sulphonic acids are almost completely ionized in watery environments even at low pH. The salts of these acids are the hydrotropes (or “sulphonates”) which include ammonium, calcium, potassium and sodium cations. In principle the salts get dissociated when in contact with water, so forming back to the acids. Because of their close chemical similarities and because much of the production of the aromatic sulphonic acids goes to manufacturing the salts, the extensive dataset for the hydrotropes can also be used as a source of read-across for endpoints in an aromatic sulphonic acid dossier. This is particularly relevant for studies that are conducted in water (e.g., ecotoxicity and biodegradation) as well as for mammalian toxicity studies where the relatively high acidity of the acid form has an immediate and harsh local effect, whereas the salt form provides an indication of potential systemic toxicity beyond the site of application or initial contac

No basis for acute toxicity classification is found.