Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Single dose, with 14 day observations. May 22-30, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Name: Formaldehyde, reaction product with ethylenediamine
CAS No.: 84066-92-2
Batch No.: PK280-61
Physical State: liquid
Colour: colourless to yellow
Purity: 100%

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Species/strain: healthy Wistar rats, Crl: WI(Han) (Full Barrier)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: male and female; the female animals were non-pregnant and nulliparous.
Age at the start of the treatment period: 7-8 weeks old

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.
Doses:
The starting dose was selected to be 300 mg/kg body weight. No compound-related
mortality was recorded for any animal of step 1.Based on these results and according to
the acute toxic class method regime, a second step was performed at a dose of 300
mg/kg body weight. No compound-related mortality was recorded for any animal of
step 2. Based on these results and according to the acute toxic class method regime, a
third step was performed at a dose of 2000 mg/kg body weight. Compound-related
mortality was recorded for all animals of step 3. Based on these results and according to
the acute toxic class method regime no further testing was required.
No. of animals per sex per dose:
Sex: female, non-pregnant, nulliparous
Number of animals: 3 per step
Control animals:
no

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Clinical signs:
The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, recumbency, ataxia, bradyxkinesia, kyphosis, wasp waist, piloerection, half eyelid-closure, diarrhoea.
Body weight:
Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain.
Gross pathology:
Macroscopic findings of surviving animals:
At necropsy, only one of the surviving animals showed treatment-related macroscopic
findings.Necropsy of all other surviving animals did not show any treatment-related
finding.
Macroscopic findings of animals not having survived until the end of the observation
period:
Necropsy revealed bloated and bloody stomach and bloody intestine.

Any other information on results incl. tables

Results per step:

 

Step

 

Sex/ No.

 

Starting Dose

(mg/kg)

 

Number         of

Animals

 

Number of Intercurrent

Deaths

 

Step1

 

Female/ 1-3

 

300

 

3

 

0

 

Step2

 

Female/ 4-6

 

300

 

3

 

0

 

Step3

 

Female/ 7-9

 

2000

 

3

 

3

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The median lethal dose of Formaldehyde, reaction product with ethylenediamine after a single oral administration to female rats, observed over a period of 14 days is: ATE cut-off (rat): 500 mg/ kg bw

Note that in a range-finder study, a dose of 1000 mg/kg/day was tolerated over 14 days and 800 mg/kg/day was tolerated over 28 days with limited adverse effects.