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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:
20.08.1985 - 10.09.1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
GLP compliance:
no
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): Meprosan
- Physical state: liquid
- Analytical purity: >99 %

Test animals

Species:
rat
Strain:
other: WISW (SPF THO)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 4799 Borchen, Germany
- Weight at study initiation: male: 124 g; female: 107 g
- Fasting period before study: 16 hrs
- Housing: 1 -5 animals each cage (Makrolon Typ III)
- Diet (e.g. ad libitum): R10 Alleindiät für Ratten, Ssniff Spezialfutter GmbH, 4770 Soest, ad libidum
- Water (e.g. ad libitum): tap water, ad libidum
- Acclimation period: 4-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15x
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.09 - 3.33 cm3/kg
Doses:
1990, 2510, 2835, 3160 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Animals were weighed before treatment and on day 1, 7 and 14; observations were recorded up to 6 hrs following treatment and daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Statistics:
Determination of LD50 according to Litchfield and Wilcoxon (J. Pharmacol. Exp. Ther. 96, 1949, p. 99)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 230 mg/kg bw
95% CL:
2 009 - 2 475
Mortality:
1990 mg/kg bw: 2/5 (male), 1/5 (female) within 4 days; 2510 mg/kg bw: 3/5 (male), 5/5 (female) within 11 days
2835 mg/kg bw: 5/5 (male), 4/5 (female) within 11 days; 3160 mg/kg bw: 3/5 (male), 5/5 (female) within 4 hours
Clinical signs:
5 - 30 min after treatment, the animals showed slight to severe sedation and ataxia, lateral and prone position, labored breathing, staggering. Later
on hypothermia, ruffled fur, trembling, bloody noses and snouts, and blood in the urine. Signs persisted in some animals until the end of the 14-day observation period, i.e.sedation, ataxia, ruffled fur, hypothermia, staggering were noted, along with a clear body weight reduction.
Body weight:
Body weight was decreased in all treated animal groups (-7% to -25%) at the end of the observation period.
Gross pathology:
Animals that died: hyperemia and distension was noted in the stomach, small intestine, and the bladder, and bloody contents were noted in these organs. Corrosion of the stomach wall was noted in some of the animals.
Animals sacrificed at termination: hyperemia, discoloring of the instestinal mucosa, swelling of the stomach mucosa was noted in some instances. Adhesions of the stomach, liver and spleen were noted in 3 survivors.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 was 2230 mg/kg bw in male and female rats in an OECD 401 study.
Executive summary:

The acute oral toxicity was determined in a valid OECD 401 study in groups of 5 male and female rats, receiving a dose of 1990, 2510, 2835, 3160 mg/kg bw by oral gavage.

The clinical signs. i.e. sedation, ataxia, ruffled fur, hypothermia and staggering, persisted in some animals until the end of the 14-day observation period. Dead animals suffered from gastro-intestinal hemorrhage as result of the corrosive activity of the isobutyric acid.

The oral LD50 was 2230 (2009 - 2475) mg/kg bw (Hüls AG, 1985).