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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 April 1986 - 06 May 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed under GLP and according to internationally accepted guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: flakes
Details on test material:
- Trade name/code: Ketjenflex-9
- Batch no.: PA 20/1/86
- Appearance: Fl akes
- Purity: Mixture of toluene sulfonamides (o/m/p= 41/8/51); water content 0.35%, sulphate content= 135 ppm
- Solubility: Insoluble in water
- Stability: Stable
- Storage: At ambient temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, Brussels, Belgium
- Age at study initiation: no data, young.
- Weight at study initiation: The body weights of the males on day 0 ranged from 354 to 435 those of the females from 225 to 273 g.
- Fasting period before study: Feed was withheld overnight before dosing till approximately 4 hours after administration of the test substance.
- Housing: Four days prior to dosing the animals were individually housed in polycarbonate cages.
- Diet (e.g. ad libitum): ad libitum, standard laboratory animal diet (RMH-By pellet diameter 10 mm), which was obtained from Hope Farms, Woerden, The Netherlands.
- Water (e.g. ad libitum): ad libitum, tap-water
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 40-80
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: 14 April 1986 - 06 May 1986

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: details not provided
- Amount of vehicle (if gavage): Fixed volume for all concentrations in ml/kg; does not exceed 10 ml/kg
- Justification for choice of vehicle: details not provided
- Lot/batch no. (if required): details not provided
- Purity: details not provided

MAXIMUM DOSE VOLUME APPLIED: does not exceed 10 ml/kg

DOSAGE PREPARATION (if unusual): no data
Doses:
1800, 2100, 2400 mg/kg bw day
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: The animals are observed for a period of 14 days, i .e. every two hours on the day of administration of the test substance and once every day thereafter. Individual body weights of the animals are determined on the day of dosing, weekly thereafter and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
The LD50 value, where possible a seperate value for males and females, is calculated from the observed mortality data, using any established statistical procedure, e.g. that of Litchfield and Wilcoxon (l949), Weil (1952) or Finney (1971).

Results and discussion

Preliminary study:
Based on literature data on the LD50 values of the separate components of the test substance and the LD50 value of a related substance as provided
by the sponsor, three dose levels were selected: 1800, 2400 and 3200 mg/kg body weight. However, the highest dose presented a too viscose suspension that could not be adequately administered as one single dose. It was therefore decided to select one dose level in between 1800 and 2400 mg/kg, namely 2100 mg/kg.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 400 mg/kg bw
Mortality:
Only in the high dose group 5 out of 10 animals died. There was no evident sex related effect. One female animal of the mid dose group had received only approximately 25% of its dose due to clogging of the test material in the dosing cannula. However this is not considered to have affected the outcome of this study, since no mortality was found in this treatment group. All deaths occurred within 3 days of dosing.
Clinical signs:
Major signs of toxicity were lethargy, unbalanced gait, dyspnea for the mid and low dose groups, and for the high dose group in addition to the afore mentioned symptoms, coma, bloody eye encrustation, absent or bloody stool and slimy salivation. All animal s which became comatose (5-3 hours postdosing) died within approximately 48 hours of that stage. For surviving animal s these signs were reversible since as of day 4 generally no more abnormalities were observed during the 14-day observation period.
Body weight:
Female group mean body weight gain of the 2400 mg/kg dose group was stagnant during the 14-day observation period. Weekly group mean body weight gain was normal for all other animals.
Gross pathology:
Macroscopic examination of animals found dead generally revealed test substance related petechiae and/or haemorrhages of the stomach frequently combined with bloody intestinal content and marked haematuria. One male of the high dose group revealed an atrofic testis, which was not considered to be test substance related. Macroscopic examination of surviving animals at the end of the study showed no test substance related gross abnormalities.

Any other information on results incl. tables

Mortality:

Sex

Dose

(mg/kg)

# deaths

Total #

animals

Day 1

Day 2

Day 3

Day

4-15

1800

0

5

0

0

0

0

M

2100

0

5

0

0

0

0

2400

2

5

0

1

1

0

1800

0

5

0

0

0

0

F

2100

0

5

0

0

0

0

2400

3

5

2

1

0

0

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LD50 value for the sexes combined was estimated to be approximately 2400 mg/kg body weight.
Executive summary:

According to OECD401 and under GLP an acute oral toxicty study was performed with o/p-TSA. Three groups of Wistar rats, each comprising 5 males and 5 females, received a single oral dose of o/p-TSA at 1800, 2100 and 2400 mg/kg body weight, respectively. Only in the high dose group 5 out of 10 animals died. There was no evident sex related effect. All deaths occurred within 3 days of dosing. Major signs of toxicity were lethargy, ataxia and dyspnea for surviving animals, whereas for dead animals also coma was observed. For surviving animals these signs were reversible since as of day 4 no more abnormalities were observed during the 14-day observation period. Macroscopic examination of animal s found dead generally revealed test substance related petechiae and/or haemorrhages of the stomach frequently accompanied by bloody intestinal content and marked haematuria. Macroscopic examination of surviving animals at autopsy revealed no treatment related gross abnormalities. The LD50 value for the sexes combined was estimated to be approximately 2400 mg/kg body weight.