Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
OECD 420 method reference not mentioned but similar protocole

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Specific details on test material used for the study:
Sample NIK-242 , batch no. 6, 8, 9, 10

Test animals

Species:
rat
Strain:
Wistar
Remarks:
from hizuoka-ken Agriculture' Co-operative Association for Laboratory Animais
Sex:
male/female
Details on test animals and environmental conditions:
- assigned randomly
- initial body weights: not stated;
- age : 6 weeks old at the start of administration
- diet: radiologically sterilized solid chow (CE-2, Crea Japan, Inc.); food and water ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
8.0, 9.5, 11.3, 13.5, and 16.0 g/kg for both sexes
No. of animals per sex per dose:
6/sex/dose group/treatment
Control animals:
yes
Details on study design:
Dosing : 1 day
Observations: 14 days. Continuous monitoring for 5 hours alter dosing, the morning of the next day, then daily thereafter body weights recorded just prior to and 1, 3, 7, and 14 days alter dosing

Pathology observations : Gross examinations were performed at necropsy and on rats dying during the study; ail organs and tissues with abnormalities and those tissues from 1 or 2 groups of animais where mortality was near 50% were fixed in 10% buffered formalin and stained with H-E; at a minimum, the following tissues were examined: brain, thymus, heart, lungs, liver, spleen, pancreas, kidneys, adrenals, testes, ovaries, uterus, stomach, small intestine, colon, mesenteric lymph node, and bone marrow; histopathological examinations of the tissues were conducted for representative cases
Statistics:
LD„ and the 95% confidence intervals were calculated from cumulative number of deaths for 14 days by the probit method or van der Waerden's area method

Results and discussion

Preliminary study:
none
Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 13 500 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 13 100 mg/kg bw
Based on:
test mat.
Mortality:
males: 11.3 g/kg (1/6), 13.5 g/kg (3/6), 16.0 g/kg (6/6)
females: 13.5 g/kg (5/6), 16.0 g/kg (5/6)
Clinical signs:
In males, hypokinesis, oligopnea, and blepharoptosis appeared immediately following dosing in the 13.5 g/kg and higher dose groups and within 5 to 15 minutes in the lower dose groups. A transparent mucous¬like substance and watery faeces occurred 15 minutes alter dosing, and oily hair coats 30 minutes alter dosing, at ail doses tested. In males that died, a lack of response to sound, recumbency, abnormal respiration, lacrimation, cyanosis and a cold sensation in the skin were observed 30 minutes to 1 hour alter dosing. Death was due to cardiac arrest following respiratory arrest. In survivors, symptoms began to disappear in 1 or 5 hours. In females, symptoms were generally the same as in males, but appeared 5 minutes alter administration.
Body weight:
No decrease in animal weight after dosing. A steady increase in weight gain was seen in ail treated groups throughout the remainder of the study.
Gross pathology:
At necropsy, in animais which died, subdural haemorrhage, and congestion were observed. Some decedent animais showed evidence of thymic haemorrhage. In all treatment groups, decedent animais also showed dilatation and cytoplasmic vacuolization of the renal tubules. Surviving animais in ail treatment groups showed no gross or histopathological abnormalities when compared to controls

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 for erythritol in an assay comparable to OECD 420 method: 13.1 g/kg in males and 13.5 g/kg in females
Executive summary:

LD50 for erythritol in an assay comparable to OECD 420 method: 13.1 g/kg in males and 13.5 g/kg in females