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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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted with a supporting substance, but according to the OECD guideline 401 and is fully GLP-compliant. As no study for the reaction mass of Glycyl-L-glutamine and potassium chloride is available, studies conducted with the two main components L-glycyl-L-glutamine and potassium chloride (such as this) were used for read-across in order to avoid unnecessary repitition of testing. As no synergistic or antagonistic effects from either of the main components are expected, the information derived from both main components is considered to be reliable for classification of the reation mass of Glycyl-L-glutamine and potassium chloride.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

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 animals

Species:
rat
Strain:
other: Bor: WISW (SPFCpb)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG
- Age at study initiation: males 8 weeks; females 9 weeks
- Weight at study initiation: males 150-164g; females 138-146g
- Fasting period before study: 16 hours before treatment
- Housing: individually in Macolon cages type II
- Diet (e.g. ad libitum): standard diet ad libitum, ssniff R, special diet for rats
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 21.6
- Humidity (%): 40-69
- Air changes (per hr): 12 hours artificial lighting / 12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Aqueous carboxymethylcellulose 0.5%
Doses:
2370 mg/kg bw
5110 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
no
Statistics:
no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 110 mg/kg bw
Mortality:
Mortality in the 2370 mg/kg bw dose group:
no mortality

Mortality in the 5110 mg/kg bw dose group:
male: no mortality
female: 2/5 females died 3 hours post application
Clinical signs:
After administration of 2370 mg/kg bw the only clinical symptoms were slight hypokinesia and decrease of muscle tone. In 4/5 male and 3/5 female animals no symptoms were detected
After administration of 5110 mg/kg bw intoxication was characterized by slight to severe hypokinesia, slight clonic convulsions, decrease of muscle tone, and loss of righting reflexes. In individual animals restrained gait, piloerection, slight tremor, diarrhea, and sunken sides occured. Ante mortem one female showed strenuose respiration.
Symptoms were present between 29 minutes and one day or lasted until death.
Gross pathology:
At necroscopy in individual male animals the testes appeared reduced in size.
Other findings:
Testes:
The testes were affected by focal and/or diffuse atrophy of the seminiferous epithelium. In minimal to moderate cases degenerative changes were observed in spermatocytes and spermatids, resulting in a reduction or absence of these cells in specific stages of the seminiferous epithelium. Spermatocytes were predominantly affected in the zygotene stage of the meiotic cell division. Degenerative changes and a delay in the maturation of spermatids occured in the first five stages of the cycle of the seminiferous epithelium. Affected tubules often had multinucleated giant cells. In marked to massive cases the epithelium of the seminiferous tubules consisted only of spermatogonia and Sertoli-cells or was characterized by the Sertoli-only change.
Diffuse atrophy of the seminiferous epithelium occured in 2/5 rats treated with 5110 mg/kg bw and in 5/5 rats treated with 2370 mg/kg bw. The finding was graded as marked to massive in animals of the high dose group and minimal to moderate in animals of the low dose group. Focal atrophy was pbserved in 1/5 and 3/5 animals treated with 5110 and 2370 mg/kg bw, respectively. It was graded slight to marked.

Epididymides:
The epididymides of animals of both dose groups had a treatment related reduction of spermatosoma. This finding was associated with the occurence of immature, multinucleated and degenerated speratids / spermatozoa. Four/5 and 5/5 animals treated with 5110 and 2370 mg/kg bw were affected by this change. It was graded slight to massive.

Ovaries:
The examined ovaries did not show any treatment related findings.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
After oral application of the test substance the LD50 was above 5110 mg/kg bw for male and female rats.