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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
N-ethyl-o(or p)-toluenesulphonamide
EC Number:
232-465-2
EC Name:
N-ethyl-o(or p)-toluenesulphonamide
Cas Number:
8047-99-2
Molecular formula:
C9H13NO2S
IUPAC Name:
N-ethyl-o(or p)-toluenesulphonamide
Test material form:
liquid: viscous
Remarks:
Colour: light yellow
Details on test material:
Ketjenflex 8 (NETSA)
Chemical name in report: N-ethyl-o/p-toluenesulfonamide (or N-substituted toluene sulphonamide)
Description: light yellow viscous liquid
Purity 100% (or 90%)

Test substance storage: at room temperature in the dark
Stability under storage conditions: stable
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

Test animals

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.

Administration / exposure

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)

Results and discussion

Effect levelsopen allclose all
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:
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 observation
Body weight:
Animals found dead showed body weight loss whereas surviving animals showed normal weekly body weight gain.
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.

Applicant's summary and conclusion

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).