N-ethyl-o(or p)-toluenesulphonamide

Endpoint summary

Description of key information

Acute oral toxicity (OECD TG 401): LD50 >5800 mg/kg bw

Acute dermal toxicity (OECD TG 402): LD50 >7945 mg/kg bw

Acute inhalation toxicity: not classified

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Aug 1985 - 03 Sep 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(adopted 12 May 1981)

GLP compliance:

yes

Test type:

standard acute method

Specific details on test material used for the study:

- Chemical name: N-substituted toluene sulphonamide
- Trade name/code: Ketjenflex 8
- Impurity: Approx. 10% o/p toluene sulfonamide
- Specific gravity: Approx. 1200 kg/m3 (at 25 ̊ C)
- Solubility: Organic solvents except petroleum hydrocarbons
- Flash point: 224 ̊ C
- Boiling point: > 340 ̊ C
- Vapour pressure: < 1mm Hg at 150 ̊ C
- Appearance: Light yellow, viscous liquid
- Storage: At ambient temperature in the dark
- Stability: Practically unlimited

Species:

rat

Strain:

Wistar

Remarks:

SPF quality - randomly bred

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Central institute for the Breeding of Laboratory Animals TNO (CPB), Zeist, The Netherlands
- Females (if applicable) nulliparous and non-pregnant: No information provided
- Age at study initiation: No information provided
- Weight at study initiation: Males: from 206 to 241 g. Females: from 136 to 157 g
- Fasting period before study: Feed was withheld overnight before dosing till approximately 3.5 to 5 hours after administration of the test substance.
- Housing: Animals were individually housed in Macrolon cages (acclimation period). The bedding material, purified saw dust (woody clean), was received from The Broekman Institute, Someren, The Netherlands.
- Diet (e.g. ad libitum): Standard laboratory animal diet (RMH-B, pellet diameter 10 mm), which was obtained from Hope Farms, Woerden, The Netherlands.
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: Quarantine period was 8 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Humidity (%): Relative humidity 50-80
- Photoperiod (hrs dark / hrs light): The artificial light sequence was 12 hours light, 12 hours dark.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 13.0 g/Kg Body weight

DOSE RANGE FINDING INVESTIGATION:
- Rationale for the selection of the starting dose: In order to establish an appropriate dose range three groups of Wistar rats, each compromising 1 male and 1 female, were dosed with a single oral dose of the test substance at 5000, 4200 and 3200 mg/Kg body weight, respectively. The female of the 4200 mg/Kg group was found dead on day 1. All animals showed signs of systemic toxicity (apathy, and reduced locomotive activity). As of day 1 no more abnormalities were observed during the 9-day observation period. Macroscopic examination at autopsy of the animal found dead showed bloody contents of the ileum; surviving animals revealed no gross abnormalities at autopsy.

Doses:

Single oral dose of the test substance at 4.2, 7.4 and 13.0 g/Kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: Day 0, 7 and 14
- Necropsy of survivors performed: no information provided
- Other examinations performed: clinical signs, body weight and pathology

Statistics:

LD50 calculation according to maximum likelihood (FINNEY)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5.8 other: g/kg/ bw

Based on:

test mat.

95% CL:

>= 4.4 - <= 7.4

Sex:

male

Dose descriptor:

LD50

Effect level:

6.9 other: g/Kg/ bw

Based on:

test mat.

95% CL:

>= 5.9 - <= 10

Sex:

female

Dose descriptor:

LD50

Effect level:

4.8 other: g/Kg/ bw

Based on:

test mat.

95% CL:

>= 0 - <= 7.5

Mortality:

In the low dose group 2 out of 10 animals died, in the medium dose group 7 out of 10 and in the high dose group 10 out of 10. There was insufficient data to assess a sex related effect. All deaths occurred within 3 days of dosing.

Clinical signs:

other: Signs of toxicity were apathy, reduced locomotive activity, labored breathing, tremors, or reduced or bloody faecal excretion. For surviving animals these signs were reversible since as of day 4 no more abnormalities were observed during the 14 days obser

Gross pathology:

Macroscopic observations at autopsy of animals found dead after day 1 revealed in 3 males and 4 females petechiae or haemorrhages of the stomach wall. In addition, 1 male and 4 females showed superficial liver necrosis in areas adjacent to the stomach, and 4 females showed marked haematuria. These findings were indicative of stomach perforation and damage to the urogenital tract, respectively. In 10 animals found dead on day 1 and in all animals sacrificed at the end of observation period, no treatment related gross abnormalities were observed.

Interpretation of results:

other: not classified

Remarks:

according to the EU classification criteria outlined in Annex I of 1272/2008/EC (CLP)

Conclusions:

The LD50 value of Ketjenflex 8 for the sexes combined amounted to approximately 5.8 g/kg body weight with a 95% confidence limit (4.4 -7.4 g/Kg body weight).

Executive summary:

Three groups of Wistar rats, each comprising of 5 males and 5 females, received a single oral dose of ketjenflex 8 at 4.2, 7.4 and 13.0 g/Kg body weight, respectively. In the low dose group 2 out of 10 animals died, in the medium dose group 7 out of 10 and in the high dose group 10 out of 10. There was insufficient data to assess a sex related effect. All deaths occurred within 3 days of dosing. Signs of toxicity were apathy, reduced locomotive activity, labored breathing, tremors, or reduced or bloody faecal excretion. For surviving animals these signs were reversible, at day 4 no more abnormalities were observed during the 14 days observation. Animals found dead showed body weight loss whereas surviving animals showed normal weekly body weight gain. Macroscopic observations at autopsy of animals found dead after day 1 revealed petechiae or haemorrhages of the stomach wall, superficial liver necrosis in areas adjacent to the stomach, and marked haematuria. These findings were indicative of stomach perforation and damage to the urogenital tract. Animals found dead on day 1 and in all animals sacrificed at the end of the study showed no treatment related gross abnormalities were observed. While the calculated LD50 for males and female were 6.9 mg/kg bw (95% CI: 5.9 - 10.0 mg/kg bw) and 4.8 mg/kg bw (95% CI: 0 - 7.5 mg/kg bw) respectively. The acute oral LD50 for the substance in male and female rats was determined to be 5.8 g/kg bw with 95% CI of 4.4 -7.4 mg/kg bw.

As a result, the substance N-Ethyl-o (or p)-toluenesulfonamide (NETSA) does not need to be classified for acute oral toxicity according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 800 mg/kg bw

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

Study period:

1958

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-guideline study, pre-GLP, doses not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Details on inhalation exposure:

Animals were exposed for 3 consecutive days of 8 hours.

No. of animals per sex per dose:

4

Control animals:

no

Key result

Sex:

male

Dose descriptor:

other: saturated vapours at 177 deg C.

Based on:

test mat.

Exp. duration:

8 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

None

Clinical signs:

other: Moderate discomfort, slight nasal discharge, inflammation, letargy.

No deaths resulted from the three days exposure. Whitish, aury vapours were given off at a sufficient rate to maintain a moderate inside the chamber. In all probability the atmosfere was kept saturated. Mild discomfort was noted within a few minutes after the start of each days exposure. This developed into moderate lethargy with mild to moderate inflammation of the nasal route. Breating remained about normal. There was moisteming of the nasal passages but only slight discharge. The animals looked normal at the start of each days test and no compications developed during a seven day holding period. The compound becomes dark in colour in one to two hours after being heated. It was comcluded that Santicizer 8 vapours given off at 350 deg F.are moderately irritating in a saturated atmoshere. They were not acutely toxic to rats.

Interpretation of results:

other: not classified

Remarks:

according to the EU classification criteria outlined in Annex I of 1272/2008/EC (CLP)

Conclusions:

No deaths occured in a 3 consecutive day 8 hours exposure of air saturated by Santicizer 8 vapours at 177 deg C .

Executive summary:

Four mature male rats (Sprague-Dawley) were placed in a metal chamber of approximately 35 liters for three consecutive eight hour days to a saturated atmosphere of Sanitizer 8 vapours produced by heating the liquid to 350 deg F (177 deg C). 250 mL of sample was placed in a three hals round bottom flask and the vapours were led into the chamber through a short lenght of hose. A gas burner was used to maintain the proper temperature. Food and water were applied ad lib. Observations were done for behaviour and since there were no deaths, all animals were held for seven days following the test. The average temperature inside the chamber was 76.0 deg F and the average humidity was 58.0%.

No deaths resulted from the three days exposure. Whitish, aury vapours were given off at a sufficient rate to maintain a moderate inside the chamber. In all probability the atmosfere was kept saturated. Mild discomfort was noted within a few minutes after the start of each days exposure. This developed into moderate lethargy with mild to moderate inflammation of the nasal route. Breating remained about normal. There was moisteming of the nasal passages but only slight discharge. The animals looked normal at the start of each days test and no compications developed during a seven day holding period. The compound becomes dark in colour in one to two hours after being heated. It was comcluded that Santicizer 8 vapours given off at 350 deg F.are moderately irritating in a saturated atmoshere. They were not acutely toxic to rats.

As a result, the substance N-Ethyl-o (or p)-toluenesulfonamide (NETSA) does not need to be classified for acute inhalation toxicity according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).

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:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: pre-GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

other: Not specified

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

Initial weight:
- Male: 1.9 kg
- Female: 1.8 and 2.2

Details on other conditions and test animal was not provided

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Remarks:

Applied undiluted

Details on dermal exposure:

Information not provided

Duration of exposure:

24 hours

Doses:

5,010 and 7,940 Mg/Kg

No. of animals per sex per dose:

1

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no information
- Necropsy of survivors performed: no information
- Other examinations performed: signs of intoxication, gross autopsy decedents, survivors

Statistics:

No information

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 7 940 mg/kg bw

Based on:

test mat.

Mortality:

Reduced appetite and activity ( three to five days)

Other findings:

Survivors ( 14 days): Viscera appeared normal

Interpretation of results:

other: Not classified

Remarks:

according to the EU classification criteria outlined in Annex I of 1272/2008/EC (CLP)

Conclusions:

The LD50 of Santicizer 8 in rabbits after 24 hours was > 7940 mg/kg bw under the conditions of this test.

Executive summary:

To determine the dermal toxicity of Santicizer 8, an acute dermal toxicity study was performed on three New Zealand albino rabbits at a dosage level of 5010 and 7940 mg/kg bw. The LD50 of the test substance after 24 hours was > 7940 mg/kg bw under the conditions of this test. Santicizer 8 therefore does not have to be classified for acute dermal toxicity.

As a result, the substance N-Ethyl-o (or p)-toluenesulfonamide (NETSA) does not need to be classified for acute dermal toxicity according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 945 mg/kg bw

Additional information

Acute oral toxicity (OECD TG 401)

Three groups of Wistar rats, each comprising of 5 males and 5 females, received a single oral dose of Ketjenflex 8 at 4.2, 7.4 and 13.0 g/Kg body weight, respectively. In the low dose group 2 out of 10 animals died, in the medium dose group 7 out of 10 and in the high dose group 10 out of 10. There was insufficient data to assess a sex related effect. All deaths occurred within 3 days of dosing. Signs of toxicity were apathy, reduced locomotive activity, labored breathing, tremors, or reduced or bloody faecal excretion. For surviving animals these signs were reversible, at day 4 no more abnormalities were observed during the 14 days observation. Animals found dead showed body weight loss whereas surviving animals showed normal weekly body weight gain. Macroscopic observations at autopsy of animals found dead after day 1 revealed petechiae or haemorrhages of the stomach wall, superficial liver necrosis in areas adjacent to the stomach, and marked haematuria. These findings were indicative of stomach perforation and damage to the urogenital tract. Animals found dead on day 1 and in all animals sacrificed at the end of the study showed no treatment related gross abnormalities were observed. While the calculated LD50 for males and female were 6.9 mg/kg bw (95% CI: 5.9 - 10.0 mg/kg bw) and 4.8 mg/kg bw (95% CI: 0 - 7.5 mg/kg bw) respectively. The acute oral LD50 for the substance in male and female rats was determined to be 5.8 g/kg bw with 95% CI of 4.4 -7.4 mg/kg bw. As a result, the substance does not need to be classified according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Acute dermal toxicity (OECD TG 402)

To determine the dermal toxicity of Santicizer 8, an acute dermal toxicity study was performed on three New Zealand albino rabbits at a dosage level of 5010 and 7940 mg/Kg. The LD50 of the test substance after 24 hours was > 7940 mg/kg bw under the conditions of this test. Santicizer 8 therefore does not have to be classified according to the EU classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Acute inhalation toxicity

Four mature male rats (Sprague-Dawley) were placed in a metal chamber of approximately 35 liters for three consecutive eight hour days to a saturated atmosphere of Sanitizer 8 vapours produced by heating the liquid to 350 deg F (177 deg C). 250 mL of sample was placed in a three hals round bottom flask and the vapours were led into the chamber through a short lenght of hose. A gas burner was used to maintain the proper temperature. Food and water were applied ad lib. Observations were done for behaviour and since there were no deaths, all animals were held for seven days following the test. The average temperature inside the chamber was 76.0 deg F and the average humidity was 58.0%.

No deaths resulted from the three days exposure. Whitish, aury vapours were given off at a sufficient rate to maintain a moderate inside the chamber. In all probability the atmosfere was kept saturated. Mild discomfort was noted within a few minutes after the start of each days exposure. This developed into moderate lethargy with mild to moderate inflammation of the nasal route. Breating remained about normal. There was moisteming of the nasal passages but only slight discharge. The animals looked normal at the start of each days test and no compications developed during a seven day holding period. The compound becomes dark in colour in one to two hours after being heated. It was comcluded that Santicizer 8 vapours given off at 350 deg F.are moderately irritating in a saturated atmoshere. They were not acutely toxic to rats.

The substance does not have to be classified for acute inhalation toxicity according to the EU classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Justification for classification or non-classification

Based on the available information, N-ethyl-o/p-toluenesulfonamide (NETSA) does not need to be classified for acute oral, dermal and inhalation toxicity, according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).