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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2nd August 1982- 30th august 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
other: OECD 401 (Acute Oral Toxicity)
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Schiff bases, benzylidene, C16-18 (even numbered) and C18-unsaturated alkyl
Molecular formula:
Not applicable - UVCB
IUPAC Name:
Schiff bases, benzylidene, C16-18 (even numbered) and C18-unsaturated alkyl

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
60 animals consisting of 30males and 30 females were selected according to body weight. Rats were housed in groups according to ses or individually in stainless steel 1/2" wire mesh cages. Size in accordance with the "Guide for the Care and Use of Laboratory Animals" of the institute of Laboratory resources, National Research Council. Waste material was removed daily and cages and feeders were sanitized every two weeks. Light cycle was 12hours light and 12hours dark. Food and water was provided ad libitum and checked daily, added or replaced as required. Cages were marked with an animal group number and dose levels. all rats had ear tags.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
0.25%
Details on oral exposure:
Rats were exposed to the test material via oral gavage at a dose volume of 5ml/kg. The vehicle was 0.25% methylcellulose
Doses:
5ml/kg for 1600, 2000, 2500, 3200 and 4000mg/kg and 10ml/kg for 5000mg/kg
No. of animals per sex per dose:
10 rats 5 females and 5 males per dose group
Control animals:
no
Details on study design:
Six groups of 10 rats ( 5 females and 5 males) were fasted for 18 hours and administered test substance at 1600, 2000, 2500, 3200 4000 and 5000mg/kg by oral gavage . The rats were observed immediately after dosing and at 1, 4 and 24hrs and once a day for 14days for pharmacotoxic, CNS effests and mortality. On the 14th day body weights were recorded. The surviving rats were sacrificed by CO2 and a gross necropsy performed.

Results and discussion

Preliminary study:
Acute Oral Single Dose Toxicity study was conducted by administering 5gm/kg (5000mg/kg) of the test article as recieved to one group of ten rats (5 males and 5 females) by oral intubation. Bodyweights were recorded prior to dosing , at death and on Day 14. Observations were made immediately and at 1, 4 and 24hrs following doesing and daily for the remainder of the study. Signs observed included; decreased activity, piloerection, decreased body tone, abnormal gait, diarrhea, abnormal stance, ptosis, flaccid body tone, chromodacryorrhea, poor grooming, exophthalmus, arched back, hypersensitivity, vascoconstriction, dried red exudate around nasal cavity and eyes, discoluoration aroung oral cavity, prostration, body drop, brownexudate around oral and nasal cavities and on ventral fur and genital-anal areas. 6 animals died at the 5gm/kg dose level.Necropsy of animals dying on study revealed discoloed and distended intestines and stomach, mottled lungs and erosions in the glandular porition of the stomach mucosa. Congested testes, hemorrhage in the thymus and adhesions between the stomach and spleen were also observed. Terminal necropsy revealed intestines congested, discolured and fluid-filled.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 420 mg/kg bw
Based on:
test mat.
Mortality:
2/10 animals died 1600mg/kg, 4/10 died at 2000 mg/kg, 5/10 died at 2500 mg/kg , 8/10 died at 3200 mg/kg and 4000mg/kg and 9/10 died at 5000 mg/kg
Clinical signs:
Signs observed includes diarrhea, hypersensitivity, piloerection, poor grooming, decreased body tone, abnormal gait, chromaturia, abnormal stance, chromodacryorrhea, decreased activity, enophthalmus, body drop, arched back, flaccid body tone, tremors and cyanosis.
Body weight:
No effect on body weight was reported.
Gross pathology:
Necropsy of those animals dying on study revealed ascites fluid and diffusely red stomach, intestines and cecum. The thymus and adrenals were distended and congested. Haemmorrhagic area were visible on stomach mucosa with the gastric mucosa completely necrotized. Congested testes were also observed. Terminal necrosy revealed no compound related lesions in the remaining animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the results from Acute Oral Toxicitystudy in rats, the calculated LD50 for the test substance was determined to be 2420 mg/kg. Therefore in accordance with the CLP guidiance for classification and labelling, the test substance is not classified for Acute Oral Toxicity. The substance is classified as Acute Oral Category 5 by GHS.
Executive summary:

Six groups of ten rats were aministered 1600, 2000, 2500, 3200, 4000mg/kg  and 1 5000mg/kg. 2 animals died 1600mg/kg, 4 died at 2000mg/kg, 5 died at 2500mg/kg , 8 died at 3200mg.kg and 4000mg/kg and 9 died at 500mg/kg. Signs observed includes diarrhea, hypersensitivity, piloerection, poor grooming, decreased body tone, abnormal gait, chromaturia, abnormal stance, chromodacryorrhea, decreased activity, enophthalmus, body drop, arched back, flaccid body tone, tremors and cyanosis. Discolouration was observed around eyes, nasal cavity, genital area and ventral fur. Necropsy of those animals dying on stughy revealed ascites fluid and diffusely red stomach, intestines and cecum. The thymus and adrenals were distended and congested. Haemmorrhagic area were visible on stomach mucosa with the gastric mucosa completely necrotized. Congested testes were also observed. Terminal necrosy revealed no compound related lesions in the remaining animals.

Based upon the results from Acute Oral Toxicitystudy in rats, the calculated LD50 for the test substance was determined to be 2420 mg/kg. There fore in accordance with the CLP guidiance for classification and labelling, the test substance is not classified for Acute Oral Toxicity. The substance is classified as Acute Oral Category 5 by GHS.