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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1990-03-01 - 1990-05-02
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The GLP study was conducted according to an internationally accepted guideline. All study parameters are given in detail.Nevertheless, according to the ECHA's practical guide 6: "How to report read-across and categories" the maximum for read-cross is 2.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): NISSEKI-SAS-40 (Mixture of benzyl-toluene and diphenyl ethan)
- Molecular formula (if other than submission substance): C14 H14
- Molecular weight (if other than submission substance): 182.27
- Structural formula attached as image file (if other than submission substance): see 'attached background material'
- Substance type: organic
- Physical state: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The animal room was maintained at a temperature of 19 - 28°C and relative humidity of 40 - 75%. On one occasion the temperature was above the upper limit specified in the protocol. This did not affect the purpose or integrity of the study. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All animals were dosed once only at the appropriate dose level by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Doses:
Range-finding Study:
500, 1000, 3000, 5000 mg/kg

Main Study a:
5000 mg/kg

Main Study b:
Due to mortalities obtained, additional groups of ten animals, (five males and five females) were treated at logarithmically spaced dose levels as follows:
2324, 3000, 3873 mg/kg
No. of animals per sex per dose:
Range-Finding Study:
1 male and 1 female per dose

Main Study:
5 males and 5 females per dose
Control animals:
no
Details on study design:
Animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Deaths and evidence of overt toxicity were recorded at each observation.

Individual bodyweights were recorded on the day of treatment (day 0), days 7 and 14, or at death.

All animals were subjected to gross necropsy examination for any macroscopic abnormalities. No tissues were retained.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 531 mg/kg bw
Based on:
test mat.
95% CL:
1 927 - 3 324
Mortality:
Dose level: 2324 mg/kg: 3/10
3000 mg/kg: 7/10
3873 mg/kg: 9/10
5000 mg/kg: 9/10
Clinical signs:
Signs of toxicity noted in all dose groups were hunched posture and pilo-erection. Animals treated with 2324, 3873 or 5000 mg/kg also showed red/brown stains around the snout, red/brown stains around the mouth and/or ataxia. Incidents of pallor of the extremities, loss of righting reflex, decreased respiratory rate and lethargy were noted in animals treated with 3000 mg/kg or greater. Incidents of ptosis and increased salivation were also noted in one male treated with 3873 mg/kg and two females treated with 5000 mg/kg showed dehydration or diuresis. All males and one female treated with 2324 mg/kg appeared normal throughout the study. All other surviving animals appeared normal three or four days after dosing.
Body weight:
One female treated with 2324 mg/kg, one female treated with 3000 mg/kg and the surviving males treated with 3873 or 5000 mg/kg all showed a reduced bodyweight gain during the study.

All other animals showed expected gain in bodyweight during the study.
Gross pathology:
Abnormalities noted at necropsy of animals that died during the study were haemorrhagic or abnormally red lungs, dark or pale liver or patchy pallor of the liver, pale spleen, pale kidneys, haemorrhage of the glandular and non-glandular gastric epithelia and haemorrhage of the small and large intestines.

No abnormalities were noted at necropsy of animals killed at the end of the study except for pale livers noted in two females treated with 2324 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) and 95% confidence limits of the test material, NISSEKI-SAS-40, in the Sprague-Dawley strain rat were estimated to be:

All animals : 2531 (1927 - 3324) mg/kg bodyweight

Males only : 2726 (2379 - 3125) mg/kg bodyweight

Females only : 2180 (1009 - 4710) mg/kg bodyweight
Executive summary:

A study was performed to determine the acute oral median lethal dose (LD50) of the test material, administered undiluted, in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity" referenced as Method B1 in Annex V of EEC Commission Directive 84/449/EEC. Following a range-finding study, four groups, each of ten fasted animals (five males and five females), were given a single oral dose of undiluted test material at dose levels of 2324 to 5000 mg/kg bodyweight. Deaths were noted one to four days after dosing. Common signs of toxicity noted were hunched posture and pilo-erection. Additional or isolated incidents of toxicity noted were ataxia, lethargy, red/brown stains around the snout, red/brown stains around the mouth, pallor of the extremities, loss of righting reflex, decreased respiratory rate, ptosis, increased salivation, dehydration and diuresis. Surviving animals appeared normal throughout the study or three or four days after dosing. Incidents of reduced bodyweight gain were noted during the study. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic or abnormally red lungs, dark or pale liver or patchy pallor of the liver, pale spleen, pale kidneys, haemorrhage of the glandular and non-glandular gastric epithelia and haemorrhage of the small and large intestines. No abnormalities were noted at necropsy of animals killed at the end of the study except for pale livers noted in two females treated with 2324 mg/kg.