Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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 434 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:
no guideline followed
Principles of method if other than guideline:
Acute subcutaneous study
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

Administration / exposure

Details on dermal exposure:
subcutaneous injection in the back
Doses:
doses of 9.5, 11.3, 13.5, 16.0 g/kg for both sexes
No. of animals per sex per dose:
6/sex/dose group/treatment
Control animals:
not specified
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 anima
is where mortality was near 50% were fixed in 10% buffered formalin and stained with H-E; at a mini
mum, the following tissues were examined: brain, thymus, heart, lungs, liver, spleen, pancreas, kid
neys, 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
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 16 000 mg/kg bw
Based on:
test mat.
Mortality:
males 16.0 g/kg (3/6) and females 16 g/kg (2/6)
Gross pathology:
At necropsy, in animais which died, subdural haemorrhage, and congestion were observed. Som
e decedent animais showed evidence of thymic haemorrhage. In all treatment groups, decedent
animais also showed dilatation and cytoplasmic vacuolization of the renal tubules. Surviving anim
ais 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 by subcutaneous route > 16g/kg in rats
Executive summary:

LD50 for erythritol by subcutaneous route > 16g/kg in rats