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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:
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
Justification for type of information:
Read-across from supporting substance (structural analogue or surrogate)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): p-toluolsulfonsaure
- Substance type: organic
- Physical state: liquid
- Analytical purity: >98%
- Impurities (identity and concentrations): 0.3% H2SO4
- Composition of test material, percentage of components:
- Isomers composition: p-TS: ca 84.6%; m-TS: ca 4.6%; o-TS: ca 10.6%
- Purity test date: August 1, 1988
- Lot/batch No.: GPAD 185
- Expiration date of the lot/batch: not provided
- Stability under test conditions: stable
- Storage condition of test material: in the dark at 20 C
- Other:

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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

Administration / exposure

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

Results and discussion

Effect levels
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:
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 symptoms were irreversible in 1 or 2 animals. Other clinical signs included abnormal gait, ptosis and piloerection in several animals from all doses on day 1 and then reversible within 2 days for males at 2000 mg/kg and females at 1250 mg/kg. For females at 1600 and 2000 mg/kg these symptoms were observed throughout the 28 day observation period.
Body weight:
At the end of 28-days, body weight increased in 2 of 3 males that survived. Increased in 2 of 3 surviving females exposed to 1250 mg/kg, and in 1 of 2 surviving females exposed to 1600 mg/kg. Body weight decreased in single surviving female exposed to 2000 mg/kg. Both increases and decreases at 28 days were at most and least +/- 27% of initial body weights.
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

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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.