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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 November 1988 to 23 December 1988
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted to an appropriate test guideline with no or minor deviations.
Reason / purpose:
reference to same study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
according to
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Details on test material:
Batch an other numbers SNC No. 1986: 88009
Toxicology reference No. St88/253Source: Shell Nederland Raffindarerij BV Rotterdam
Date received: 18 Oct 1988
Appearance: clear colourless liquid
Analysis: 94.51-97.51% cis isomer with 1.5% trans isomer
Density: 1.224 g/mL @ 15.2C
Date released 18 Nov 1988
Storage: dark at ambient temperature
Stability: stable for the duration of the study (no changes from 21 Nov1988 to 19 Jan 1989
Used undiluted in oral test

Test animals

Fischer 344
Details on test animals and environmental conditions:
Fischer 344 rats aged 8-9 weeks were obtained from Charles River U.K. Ltd. On arrival they were housed in single sex groups of up to 12 rats to a cage. The animals were quarantined for a minimum of five days in a non-barriered animal room with access restricted to essential personnel. At least five days before dosing the animals were rehoused (as single sex groups of up to four rats) in cages with stainless steel wire-mesh walls, floors and tops. Each cage measured 38 cm x 25 cm x 18 cm. Paper-lined trays for excreta were placed beneath each cage and changed three times weekly. A pelleted diet (PRD, Labsure Animal Foods) and water from the public supply were provided ad libitum. There were no excursions of animal room environmental
conditions beyond target values of 19° to 23°C and 30% to 70% R.H. that were considered to have influenced the outcome of the study. Lighting (fluorescent tubes) was automatically controlled to provide a 12 hour day and 12 hour night. Animals assigned to the study were identified by cage-labels displaying the animal numbers, experiment number, sex and dose-level and by ear-notches denoting the animal number.

Administration / exposure

Route of administration:
oral: gavage
unchanged (no vehicle)
Details on oral exposure:
Single dose by gavage.
38, 51, 68, 90, 120, 160, or 213 mg/kg bodweight
No. of animals per sex per dose:
Control animals:
Details on study design:
Groups of five male and five female rats were fasted overnight, weighed and given a single dose of the test material by gavage, using a ball pointed cannula and syringe. Approximately three hours after dosing on Day ). the animals were allowed food again ad libitum.

A careful clinical examination was made up to three times daily for the first three days and once daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 7 and Day 14 bodyweights were recorded, and changes in bodyweight calculated.

All animals were subject to necropsy. Animals surviving to the end of the study were killed by an intraperitoneal injection of sodium pentobarbitone. The cranial, thoracic and abdominal cavities and viscera were examined and any gross pathological changes recorded.

The 14 day LD50, 95% confidence limit, and dose morality slope were calculated using a method based on probit analysis (Finney 1977)

Results and discussion

Effect levelsopen allclose all
Dose descriptor:
Effect level:
93 mg/kg bw
95% CL:
76 - 113
Remarks on result:
other: slope = 6.4
Dose descriptor:
Effect level:
78 mg/kg bw
95% CL:
68 - 90
Remarks on result:
other: slope not estimated
Dose descriptor:
Effect level:
85 mg/kg bw
95% CL:
76 - 96
Remarks on result:
other: slope = 8.7
Mortalities occurred on days 1,2, and 3. Only 3 rats survived treatment at 90 mg/kg and above; the majority of deaths occurred within 4 hours of dosing.
Clinical signs:
Common signs of reaction to treatment observed among rats dosed at 38, 51, or 68 mg/kg were limited to voiding of soft faeces or diarrhoea within 4 hrs of dosing and piloerection and/or unkempt appearance druing day 2. Recovery of surviving rats was complete by day 3. Principal clinical signs observed prior to death were increased lachrymation and salivation, abasia or taxia, and diarrhoea. Less commonly lethargy, cyanosis, and unkempt appearance were observed and isolated cases of hypothermia, piloerection and hunched posture were observed.
Body weight:
All surviing rats gained weight relative to their day 1 body weight.
Gross pathology:
Principal abnromalities found in decedents were abnormal contents, inflammation and haemorrahage of the stomach, darkening of the liver, lung congestion and discolouration of the renal medulla. No macroscopic abnormalities were found in surving animals.

Any other information on results incl. tables

Mortality following acute oral adminstration of test material
Dose M F  M/F
38 0/5 0/5 0/10
51 0/5 0/5 0/10
68 0/5 0/5 0/10
90 3/5 5/5 8/10
120 5/5 5/5 10/10
160 4/5 5/5 9/10
213 5/5 5/5 10/10

Applicant's summary and conclusion

Interpretation of results:
Migrated information Criteria used for interpretation of results: EU
The acute oral LD50 of the undiluted in test material in rats (males and females combined) was 85 mg/kg body weight (95% confidence interval 76-96 mg/kg).
LD50 of males only was 93 mg/kg (76 to 113 mg/kg 95% CI)
LD50 of females only was 78 mg/kg (68 to 90 mg/kg 95% CI)
Executive summary:

A GLP Compliant acute oral toxicity study has been completed in accordance with OECD Guideline 401. The acute oral LD50 of the undiluted in test material in rats was 85 mg/kg body weight (95% confidence interval 76-96 mg/kg).

LD50 of males only was 93 mg/kg (76 to 113 mg/kg 95% CL)

LD50 of females only was 78 mg/kg (68 to 90 mg/kg 95% CL)