Erythritol

Acute Toxicity: oral

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

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Erythritol

EC Number:

205-737-3

EC Name:

Erythritol

Cas Number:

149-32-6

Molecular formula:

C4H10O4

IUPAC Name:

butane-1,2,3,4-tetrol

impurity 1

Reference substance name:

unknown impurities

IUPAC Name:

unknown impurities

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 or test system 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 levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 13 500 mg/kg bw

Based on:

test mat.

Effect levels 2

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:

other: 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 minut

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