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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
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
PM Number: 03041-00
CAS Registry Number: 000094-60-0
HAEL Laboratory Number: 95-0212
EAN: 907570
SRID or Lot I.D. Number: X24652-38
Physical State and Appearance: Colorless liquid
Received at Performing Laboratory: August 24, 1995

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Housing:
All animals were individually housed in suspended, stainless-steel, mesh cages.

Environmental Conditions:
A photoperiod of 12 hours light from 6 a.m. to 6 p.m. was maintained. Room temperature was maintained at 66-71 oF. Relative humidity was maintained at 4 7-61 %.

Diet and Water:
PMI,. Feeds, Inc. Certified Rodent Diet (5002) pellets and water (Monroe County (NY) Water Authority) were available ru!. libitum. No known contaminants which would interfere with the outcome of the study were expected to be present in feed or water from these sources. Analyses of feed and semi-annual analyses of water are maintained on file within the testing laboratory.

Isolation:
Animals were isolated and monitored for at least five days after arrival to the testing facility.

Animal Identification:
All animals were identified by cage numbers and uniquely-numbered metal ear tags.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Control animals:
no
Details on study design:
Randomization:
A clinical examination was performed on each animal to ensure that only healthy animals wereutilized. The procedure for including animals in the study was to randomly select and assignanimals from the same shipment to the study. Randomization was done by computergenerated lists using the Automated Animal Toxicology System. After assignment of animals to the study, the body weights were determined to ensure that individual body weights did not exceed 20% of the mean weight for each sex.

Clinical Observations:
Animals were observed three times on the day of dosing (Day 0), and once each day thereafter for the duration of the experiment. Observations included, but were not limited to, changes in the skin; fur; feces; urine; eyes; mucous membranes; respiratory, circulatory, and autonomic and central nervous systems; somatomotor activity; and behavior pattern.

Body Weight Determinations:
Body weights were collected on Days 0 (prior to treatment), 7, and 14.

Necropsy
Animals that died during the study were necropsied as soon as possible. Surviving animals were necropsied at the completion of the 14-day observation period.
Statistics:
The LD50 was obtained using the method of Wei! (1952). The results were as follows:

LD50 for male rats: 5000 mg/kg (95% C.I. = No range calculable)
LD50 for female rats: 2812 mg/kg (95% C.I. = 2357- 3354 mg/kg)

No dose/mortality curve was constructed since graphs become statistically useful only with the use of large numbers of animals and dose groups.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2 812 mg/kg bw
Based on:
test mat.
Mortality:
For male rats, mortality was 40% at a dose of 5000 mg/kg. For the females, mortality was 20% at 2500 mg/kg and 100% at 4000 and 5000 mg/kg. No mortality was noted after Day 2 of the study for any group. Details are presented in Table 1.
Clinical signs:
Abnormal clinical signs evident during the study included slight to severe weakness, prostration, diarrhea, and a reduced amount or lack of feces. Weakness was noted only on the day of dosing or the day following dosing. Severe weakness and prostration were only seen prior to death. By Day 2 of the study, all surviving animals appeared clinically normal. The time of each observation and the number of animals involved at each dose level are listed in Table 2.
Body weight:
All animals which survived to scheduled necropsy gained weight during both weeks of the study. Details are presented in Table 3.
Gross pathology:
The major treatment-related changes observed at necropsy provided evidence that the test material was a gastric irritant. These changes included necrosis and hemorrhage in the glandular gastric mucosa and the presence of increased amounts of mucus in the small intestines. Selected organs from two females that died on Day 2 of the study were processed for microscopic examination.

Any other information on results incl. tables

Table 1: Mortality

DOSE (mg/kg)

 NUMBER OF RATS EXPOSED (Male, Female)   NUMBER OF DEATHS (Male, Female)  TIME OF DEATH
 2500  0,5  NA,1  Day 1
 4000  0,5  NA,5  Day 1 or 2
 5000  5,5  2,5  Day 1 or 2
 NA = not applicable

Table 2: Clinical Observations

 DOSE (mg/kg) TIME  CLINICAL SIGNS  NUMBER OF AFFECTED ANIMALS 
 2500  Day 0

appeared clinicall normal

slight weakness

4/5 Females

1/5 Females

 2500  Day 1

death

appeared clinically normal

1/5 Females

4/4 Females 

 2500  Days 2 -14 appeared clinically normal  4/4 Females
 4000  Day 0

 appeared clinically normal

slight weakness

moderate weakness

 2/5 Females

1/5 Females

2/5 Females

 4000  Day 1

death

moderate weakness

reduced amount of feces

3/5 Females

2/2 Females

2/2 Females 

 4000  Day 2 death 2/2 Females
 5000  Day 0

slight weakness

moderate weakness

severe weakness

prostration

diarrhea

3/5 Males

4/5 Females

2/5 Males, 1/5 Females

1/5 Males

1/5 Females

 5000  Day 1

death

slight weakness

moderate weakness

lack of feces

diarrhea

2/5 Males, 4/5 Females

3/5 Males

1/1 Females

3/5 Males

1/1 Females

 5000  Day 2

death

appeared clinically normal

1/1 Females

3/5 Males

 5000  Days 3 -14 appeared clinically normal 3/5 Males

Table 3: Body Weight

 animal no. (sex) DOSE (mg/kg)  Day 0 Body Wt. (gm) Day 7 Body Wt. (gm)  Day 14 Body Wt. (gm) 
 591 (M) 5000  205 266 316
 592 (M) 5000  206 265 320
 593 (M) 5000  201 died day 1  *
 594 (M) 5000  214 died day 1  *
 595 (M) 5000  200 264 321
 651 (F) 2500  157 207  240 
 652 (F) 2500  163 213  254 
 653 (F) 2500  163 died day 1  *
 654 (F) 2500  158 212  239 
 655 (F) 2500  166 219  240 
 656 (F) 4000  155 died day 1   *
 657 (F) 4000   162 died day 2  (133)
 658 (F) 4000  157 died day 1   *
 659 (F) 4000  156 died day 1   *
 660 (F) 4000  160 died day 2  (132)
 596 (F) 5000  168 died day 1  *
 597 (F) 5000  177 died day 2  (153)
 598 (F) 5000  173 died day 1  *
 599 (F) 5000  181 died day 1  *
 600 (F) 5000  184 died day 1  *

* A terminal body weight was not recorded for any animal which died within 24 hours of dosing.

Applicant's summary and conclusion

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
Based on the oral LD50 for male and female rats, the test material was classified as slightly toxic in rats according to the criteria set forth by Hodge and Sterner (1949) and requires no toxicity classification as defined in the 18th Adaptation on the EC Classification, Packaging, and Labelling of Dangerous Substances.
Executive summary:

In this acute oral toxicity study, mortality was 40% at a dose of 5000 mg/kg for male rats. For female rats, mortality was 20% at 2500 mg/kg and 100% at 4000 and 5000 mg/kg. No mortality was noted after Day 2 of the study. Abnormal clinical signs evident during the study included slight to severe weakness, prostration, diarrhea, and a reduced amount or lack of feces. Weakness was noted only on the day of dosing or the day following dosing. Severe weakness and prostration were only seen prior to death. By Day 2 of the study, all surviving animals appeared clinically normal. All animals which survived to termination of the 14-day observation period gained weight. The cause of death for rats which died after exposure to the test material was not determined. However, necrosis and hemorrhage in the glandular gastric mucosa may have contributed to the deaths. Based on these findings at necropsy, the test material was considered to be a gastric irritant. The acute oral LD50 for this test material was greater then 5000 mg/kg for male rats and was calculated to be 2812 mg/kg for female rats. Based on the oral LD50 for male and female rats, the test material was classified as slightly toxic in rats according to the criteria set forth by Hodge and Sterner (1949) and requires no toxicity classification as defined in the 18th Adaptation on the EC Classification, Packaging, and Labelling of Dangerous Substances.