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Description of key information

Read across: Oral: LD50 10,000 -20,000 mg/kg, rats
Read Across: Dermal: LD50 > 2000 mg/kg, rats, limit test

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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Between 28 February 1972 and 21 March 1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study not conducted to guidelines or GLP.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Adult albino male Sprague-Dawley rats were fasted for 24 hours, then given a single dose and placed in screen bottom cages with free access to water and laboratory chow for a two week observation period.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20000 mg/kg bw
Doses:
5000, 10000, 20000 mg/kg bw
No. of animals per sex per dose:
6 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
Use of statistics not indicated.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 10 000 - < 20 000 mg/kg bw
Remarks on result:
other: 95% CL not indicated
Mortality:
5/6 males died on the third day following dosing in the 20000 mg/kg bw group.
Clinical signs:
No data.
Body weight:
No data.
Gross pathology:
No data.

Table 2: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

 

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity (#/total)

Male

Female

Combined

Male

Female

Combined

5000

0/6

0/0

0/6

 

unknown

unknown

unknown

 10000 0/6   0/0  0/6    unknown  unknown  unknown
 20000  5/6  0/0  0/6  72  unknown  unknown  unknown
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
Mortality occurred at 20000 mg/kg bw. The LD50 is considered to be between 10000 and 20000 mg/kg bw but has not been determined precisely.
Executive summary:

In an acute oral toxicity study, groups of Sprague-Dawley rats (6 males) were given a single oral dose of C14-24 alkaryl calcium salt derivatives at 5,000, 10,000 or 20,000 mg/kg bw and observed for 14 days. Mortality occurred at 20,000 mg/kg bw, therefore the LD50 is considered to be between 10,000 and 20,000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD Guidelines and to GLP, but not fully reported.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Approximately 24 hour prior to topical application of the test material, the hair of each control and treated animal was closely clipped.
A single dose of 2000 mg/kg of the undiluted test material was administered dermally to five male and female animals.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Dose level: 2 g/kg
Dose volume not specified
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On day of dosing and day 7 and 14 following dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs observed each day
Statistics:
None, there was no mortality.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: 95% CL not indicated. LD50 is greater than 2000 mg/kg bw.
Mortality:
Mortality did not occur in treated animals.
Clinical signs:
No clinical signs of toxicity were observed in treated animals.

Body weight:
Significant decreases in bodyweight were observed in treated males on days 2, 7 and 14.
Gross pathology:
Skin irritation was observed for all treated animals. Multiple pinpoint scabs were observed in 3 treated males and 1 treated female.

Table 2: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

Dose
(mg/kg bw)

Conc.
in vehicle (%)*

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity (#/total)

Male

Female

Combined

Male

Female

Combined

Control

 0/5

0/5 

 0/10

 

 0/5

0/5 

 0/10

2000

 0/5

 0/5

0/10 

 

 5/5

 5/5

10/10

No signs of systemic toxicity were observed. All treated animals exhibited skin irritation. Significant differences in mean body weight were observed between treated and control males on days 2, 7 and 14. At necropsy, multiple pinpoint scabs were observed in three treated males and one treated female.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
No mortality occurred at a maximum tested level of 2000 mg/kg bw and the study has been completed as a limit test. The LD50 is considered to be more than 2000 mg/kg.
Executive summary:

In an acute dermal toxicity study, groups of Sprague-Dawley rats (5/sex) were given a single dermal dose of the calcium sulfonate read across substance (Analogue of CAS 70024 -69 -0), at 2000 mg/kg bw and observed for 14 days. No mortality occurred in this limit test; therefore an exact LD50 has not been determined. The test article, when administered dermally as received to 5 male and 5 female Sprague Dawley rats had an acute dermal LD50 of greater than 2.0 g/kg. No evidence of systemic toxicity was observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity data of read across substances:

In the key acute oral toxicity study (Swan, 1972), Sprague-Dawley rats (6 males) were given a single oral dose of the calcium sulfonate read across substance, CAS 70024-69-0, at doses of 5,000, 10,000 or 20,000 mg/kg bw. Thereafter, the animals were observed for 14 days. Mortality occurred only at 20,000 mg/kg dose group. Therefore, the LD50 value is between 10,000 and 20,000 mg/kg bw.

A number of supporting acute oral toxicity studies with calcium sulfonate read across substances in rats also revealed that the LD50 values are above the limit for classification.

In one supporting acute oral toxicity study (Sanitised, F., 1989), Sprague-Dawley rats (5/sex/dose) were given a single oral dose (5,000 mg/kg bw) of the calcium sulfonate read across substance (analogue of 70024-69-0). Thereafter the animals were observed for 14 days. No mortality occurred in this limit test, therefore the LD50 is above 5,000 mg/kg bw.

Furthermore, another supporting study investigating the acute oral toxicity of the calcium sulfonate read across substance, CAS 115733-09-0, is available (Sanitised, A., 1981). In this study, Sprague-Dawley rats (5/sex/dose) were given a single oral dose of 5,000 mg/kg bw. Thereafter the animals were observed for 14 days. No mortality occurred in this limit test, therefore the LD50 is above 5,000 mg/kg bw.

In one supporting study (Sanitised, C., 1984) to assess the acute oral toxicity of the calcium read across substance (CAS 68783-96-0), groups of Sprague-Dawley rats (5/sex/dose) were given a single oral dose of the test item at 5,000 mg/kg bw and observed for 14 days. No mortality occurred in this limit test, therefore an LD50 has not been determined. The test article, when administered as received to 5 male and 5 female Sprague-Dawley rats, had an acute oral LD50 of greater than 5,000 mg/kg.

Considering the acute oral toxicity study (Sanitised, E., 1985), groups of Sprague-Dawley rats (5/sex/dose) were given a single oral dose of the calcium read across substance (CAS 61789-86-4) at doses of  0 or 5000  mg/kg bw and observed for 14 days. No mortality occurred in this limit test, therefore the LD50 has not been determined. The test article, when administered in peanut oil to 5 male and 5 female Sprague-Dawley rats, had an acute oral LD50 of greater than 5;000 mg/kg.

In another supporting study referring to the acute oral toxicity (Ohees, 1968a) adult albino male rats of the Sprague-Dawley strain, 200 - 300 grams in weight, were treated with the calcium read across substance (CAS 61789-86-4) for the evaluation of the acute oral toxicity. The animals were given a single calculated dose and observed for a two week period at the dosage levels of 5,000 mg/kg, 10,000 mg/kg and 20,000 mg/kg. A LD50 in excess of 20,000 mg/kg of body weight was found.

In another supporting study (Regel, 1970),the acute oral toxicity of the calcium sulfonate read across substance (CAS 61789-86-4) was assessed. Adult albino male rats of the Sprague-Dawley strain were given single calculated doses (5,000 mg/kg and 10,000 mg/kg) of the test item and observed for a two week period. Under the specified test conditions the substance has an estimated oral LD50 in excess of 10,000 mg/kg bw.

Referring to an additional supporting study (Ohees, 1968b), adult albino male rats of the Sprague-Dawley strain, 200-300 grams in weight, were treated with the calcium sulfonate read across substance (CAS 61789-86-4) to identify the acute oral toxicity. The animals were given a single calculated dose via stomach tube syringe and observed for a two week period. The concentration of test material was 50% in corn oil. The number of animals used per dose was 6 males (at a dose of 5,000 mg/kg), 2 males (at a dose of 10,000 mg/kg) and 2 males (at a dose of 20,000 mg/kg). Under the conditions specified the test substance has an estimated oral LD 50 in excess of 20,000 mg/kg bw.

In addition to the above mentioned studies, another supporting study is given for this endpoint. In order to investigate the acute oral toxicity of the calcium sulfonate read across substance (CAS 61789-86-4)in rats (Gabriel, 1981), five groups of five male albino rats of the Sherman-Wistar strain weighing between 200 and 300 grams were treated with the following dosage levels: 1,000, 2,000, 4,000, 8,000 mg/kg and 16,000 mg/kg. Therefore, the LD50 is greater than 16,000 mg/kg.

In accordance with EU CLP (Regulation (EC) No. 1272/2008), classification is not required for acute oral toxicity or specific target organ effects.

Acute dermal toxicity data of read across substances:

In the key acute dermal toxicity study (Sanitised, G., 1989), groups of Sprague-Dawley rats (5/sex) were given a single dermal dose of the calcium sulfonate read across substance, (Analogue of CAS 70024-69-0), at 2,000 mg/kg bw and observed for 14 days. No mortality occurred in this limit test. The acute dermal LD50 was greater than 2,000 mg/kg. No evidence of systemic toxicity was observed.

An acute dermal toxicity supporting study with another calcium sulfonate read across substance (CAS 115733-09-0) in male and female New Zealand white rabbits (5/sex) were treated with a single dose of 5,000 mg/kg bw dermally for 24 h and observed for 14 days (Sanitised, B., 1981). As no mortality occurred, this study also showed the LD50 value > 5,000 mg/kg bw and thereby to be above the limit for classification.

Furthermore, in an additional supporting study (Sanitised, J., 1993) to investigate the acute dermal toxicity, groups of New Zealand White rabbits (5/sex) were given a single dermal dose of the calcium sulfonate read across substance (CAS 68783-96-0) at 2,000 mg/kg bw and observed for 14 days. No mortality occurred in this limit test; therefore an LD50 has not been determined. The test article, when administered dermally as received to 5 male and 5 female New Zealand White rabbits had an acute dermal LD50 of greater than 2,000 mg/kg. No evidence of systemic toxicity was observed.

In another supporting study (Costello, 1986), the acute dermal toxicity of the calcium sulfonate read across substance (CAS 61789-86-4) was investigated in New Zealand White rabbits. The test article was dosed as supplied, at a dose level of 4,000 mg/kg. A group of 10 rabbits (5 males & 5 females) with healthy intact skin was used. The treated area was covered with a large porous gauze patch. The dressings were removed after 24 hours and any excess material removed, where practical, using water or an appropriate solvent. The animals were observed for a 14 day period for signs of toxicity (systemic and topical) and for mortalities. In males the symptoms after removal of the substance and the patch were mild erythema and mild to severe oedema.  At 7 days mild to moderate erythema and slight to severe oedema were noted. Dry flaking skin was noted for 2/5 animals at 9 days and for 1/5 animals at 13 days. At 14 days slight to mild skin irritation was noted. However, all animals appeared normal throughout the 14 day observation period. In females the symptoms were the same, with the following derivations: Mild to moderate erythema and mild to severe oedema after 24 hours. Dry flaking skin was noted for 2/5 animals at 9 days. At 14 days mild to moderate skin irritation was noted. The death of 1/5 animals on day 9 was not preceded by any adverse symptoms. A lack of faecal material in the cage pan on days 9 through 11 and signs of dehydration on days 10 and 11 were noted for 1/5 animals. Other than the above observations all animals appeared normal throughout the 14 day observation period. In conclusion, the test article when dosed as supplied appears to have an acute dermal LD50 greater than 4.0 g/kg (4,000 mg/kg bw, respectively).

In accordance with EU CLP (Regulation (EC) No. 1272/2008), classification is not required for acute dermal toxicity or specific target organ effects.

Acute inhalation toxicity of read across substances:

Testing by the inhalation route is inappropriate since exposure of humans via inhalation is unlikely due to the low vapour pressure (0.01 Pa at 25 °C ) of the read-across substance (CAS 231297 -75 -9) of benzenesulfonic acid, di-C10 -14 -alkyl derivs., calcium salts.

Therefore, the potential for the generation of inhalable forms is low.

In accordance with REACH regulation, Annex VIII, section 8.5.2, column two, testing for acute inhalation toxicity can be waived.

As a weight-of-evidence approach, the acute inhalation toxicity of the calcium sulfonate read across substance (CAS 61789-86-4, product as manufactured diluted in mineral oil (65/35)) was investigated in CD (Sprague-Dawley derived) rats according to EPA OPP 81-3 (Acute inhalation toxicity). The substance (1.9 mg/L as maximum attainable respirable aerosol) was administered for 4 hours (whole-body exposure) into the breathing zone of the animals (5 male and 5 female rats) as an aerosol. The animals were observed for additional 14 days after exposure. The mean achieved atmosphere concentration was 1.9 mg/L (nominal atmosphere concentration 41 mg/L). The mean mass median aerodynamic diameter was 4.2 µm, and the inhalable fraction (< 10 µm) was 93 %. Clinical signs and mortality rates were determined at approximately fifteen-minute intervals during the first hour of exposure and hourly for the remainder of the exposure period. All animals were observed individually upon removal from the chamber (half-hour after exposure was completed) and hourly for two hours post-exposure. Detailed physical observations were recorded at each interval. During days 2 - 15 (post-exposure), detailed observations were recorded for animals once daily; viability was assessed twice daily. The animals were sacrificed at the end of the study, dissected and examined macroscopically. The symptoms in this group were reduced activity, closed eyes and in a few animals laboured breathing towards exposure completion. Signs exhibited by animals upon removal from the chamber and during the two-hour-post exposure observation period on day 1 included secretory signs, some respiratory signs, hunched appearance and matted coats. During test week 1, test animals exhibited decreasing signs of treatment such as secretory signs and matted coat. These signs mostly abated by day 8 and during test week 2, animals exhibited few continuing signs of treatment. No animal died (mortality 0 %). The body weights of the animals were slightly less than pre-test values after test week 1. This was considered a minimal response to exposure, because in test week 2 the body weights were considered unremarkable. The gross pathology did not reveal effects of the test material. Therefore the LC50 value is > 1.9 mg/L.

In accordance with EU CLP (Regulation (EC) No. 1272/2008) , classification is not required for acute inhalation.


Justification for selection of acute toxicity – oral endpoint
best study available

Justification for selection of acute toxicity – inhalation endpoint
Inhalation is not relevant route of exposure.

Justification for selection of acute toxicity – dermal endpoint
best study available

Justification for classification or non-classification

The calcium sulfonate read across substance, (CAS 70024 -69 -0), had an acute oral LD50 between 10,000 and 20,000 mg/kg bw. In addition, several supporting acute toxicity studies for calcium sulfonate read across substances revealed LD50 values above the limit for classification. Concerning the acute dermal toxicity, the calcium sulfonate read across substance, (Analogue of CAS 70024-69-0), had an acute dermal LD50 of greater than 2000 mg/kg. Moreover, the calcium sulfonate read across substance, (CAS 115733-09-0), also had an LD50 value above the limit for classification. Concerning the acute toxicity after inhalatory exposure, first of all the substance does not bear a significant risk by this route of exposure. Moreover, two calcium read across substances (CAS 61789 -86 -4 and CAS 68783 -96 -0) were investigated and an LC50 value aboe 1.9 mg/L (the maximum attainable concentration) was found.

Therefore, Benzenesulfonic acid, di-C10 -14 -alkyl derivs., calcium salts does not meet the criteria for classification and labelling for oral, dermal or inhalatory toxicity in accordance with European Regulation (EC) No. 1272/2008.

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