Urea, polymer with ethanedial

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 11, 2012 - December 12, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Oligomerisation reaction products of glyoxal and urea.

EC Number:

610-945-6

Cas Number:

53037-34-6

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance).

IUPAC Name:

Oligomerisation reaction products of glyoxal and urea.

Details on test material:

- Name of test material (as cited in study report): NOPCOTE 1661
- Physical state: Clear, light yellow solution
- Analytical purity: 46% in water solution.
- Lot/batch No.: 79389
- Expiration date of the lot/batch: 11 January 2013
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld.- Age at study initiation: Young healthy adult rats, approximately 8-9 weeks old.- Weight at study initiation: 171 - 190 g.- Fasting period before study: The night before treatment the animals will be fasted. - Housing: 3 animals/cage.- Diet (e.g. ad libitum): Ad libitum.- Water (e.g. ad libitum): Ad libitum.- Acclimation period: 5-6 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 19.9 – 24.1°C- Humidity (%): 30 - 52 %.- Air changes (per hr): 15-20 air exchanges/hour .- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

(distilled)

Details on oral exposure:

VEHICLE:- Amount of vehicle (if gavage): 200 mg/mL- Lot/batch no. (if required): 3450611MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bwDOSAGE PREPARATION (if unusual): The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle. The formulation container was stirred continuously up to finishing the treatment. The purity factor was 2.18, therefore the dose to be adjusted was 2000 x 2.18 mg/kg bw prepared in distilled water at a dose volume of 10 ml/kg bw. With this the dose level was 2000 mg/kg bw referring to the dry component (46%) of the test item.CLASS METHOD (if applicable)- Rationale for the selection of the starting dose: In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females rats per group (group 1 and confirmatory group 2).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and Day 14 before necropsy.- Necropsy of survivors performed: Yes, all animals were subjected to a necropsy and a macroscopic examination.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Treatment did not cause mortality.

Clinical signs:

other: Treatment caused decreased activity, hunched back and piloerection.

Gross pathology:

Treatment was not associated with any test item related gross findings.

Any other information on results incl. tables

Table 1. Clinical observations.

 

Dose level: 2000 mg/kg bw, Treatment on day 0.                                     Sex: Female.

Cage No.	Animal number	Observations	Observation days												Frecuency
			0						1	2	3	4	5	6-14
			30’	1h	2h	3h	4h	6h
1	8156	Symptom Free	-	-	-	-	-	-	-	+	+	+	+	+	13/20
		Activity decreased	-	-	-	1	1	-	-	-	-	-	-	-	2/20
		Hunched back	+	+	+	+	+	+	-	-	-	-	-	-	6/20
		Piloerection	-	-	+	+	+	+	+	-	-	-	-	-	5/20
	8157	Symptom Free	-	-	-	-	-	-	+	+	+	+	+	+	14/20
		Activity decreased	-	-	-	1	1	-	-	-	-	-	-	-	2/20
		Hunched back	+	+	+	+	+	+	-	-	-	-	-	-	6/20
		Piloerection	-	-	+	+	+	-	-	-	-	-	-	-	3/20
	8158	Symptom Free	-	-	-	-	-	-	+	+	+	+	+	+	14/20
		Activity decreased	-	-	-	1	-	-	-	-	-	-	-	-	1/20
		Hunched back	+	+	+	+	+	+	-	-	-	-	-	-	6/20
		Piloerection	-	-	+	+	+	-	-	-	-	-	-	-	3/20
2	8159	Symptom Free	-	-	-	-	-	-	+	+	+	+	+	+	14/20
		Hunched back	+	+	+	+	+	+	-	-	-	-	-	-	6/20
		Piloerection	-	-	-	+	+	-	-	-	-	-	-	-	2/20
	8160	Symptom Free	-	-	-	-	-	-	+	+	+	+	+	+	14/20
		Hunched back	+	+	+	+	+	+	-	-	-	-	-	-	6/20
		Piloerection	-	-	-	+	+	-	-	-	-	-	-	-	2/20
	8161	Symptom Free	-	-	-	-	-	-	+	+	+	+	+	+	14/20
		Hunched back	+	+	+	+	+	+	-	-	-	-	-	-	6/20
		Piloerection	-	-	-	+	+	-	-	-	-	-	-	-	2/20

Remarks:

+ = present                          - = absent

h = hour (s)                          ‘ = minute

Frequency of observation = number of occurrence of observation / total number of observations

Severities: 1 = Slight/Small/Few; 2 = Moderate/Medium; 3 = Marked/Large/Many

 

  

Table 2. Body weight data.

 

Dose level: 2000 mg/kg bw, Treatment on day 0.                                     Sex: Female.

Cage No.	Animal number	Body weight (g) Days				Body Weight Gain (g)
		-1	0	7	14	-1 - 0	0 - 7	7 - 14	-1 - 14
1	8156	191	181	203	224	-10	22	21	33
	8157	200	184	224	252	-16	40	28	52
	8158	198	187	217	229	-11	30	12	31
2	8159	185	171	198	205	-14	27	7	20
	8160	195	189	218	226	-6	29	8	31
	8161	199	190	221	238	-9	31	17	39
Mean:		194.7	183.7	213.5	229.0	-11.0	29.8	15.5	34.3
Standard deviation:		5.8	7.0	10.5	15.6	3.6	5.9	8.1	10.6

 

  

Table 3. Necropsy findings.

 

Dose level: 2000 mg/kg bw, Treatment on day 0.                                     Sex: Female.

Cage No.	Animal number	Necropsy Day	External Observations	Internal Observations	Organ/Tisuue
1	8156	Day 14	No external observations recorded	No internal observations recorded	Not applicable
	8157	Day 14	No external observations recorded	No internal observations recorded	Not applicable
	8158	Day 14	No external observations recorded	No internal observations recorded	Not applicable
2	8159	Day 14	No external observations recorded	No internal observations recorded	Not applicable
	8160	Day 14	No external observations recorded	No internal observations recorded	Not applicable
	8161	Day 14	No external observations recorded	No internal observations recorded	Not applicable

 

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 value of the test substance was >2000 mg/kg bw in female rats.

Executive summary:

The single-dose oral toxicity was performed according to OECD 423 Guideline and EU B.1tris Method (acute toxic class method) in female CRL: (WI) rats. Two groups (one confirmatory group) of three rats were exposed by single oral treatment to 2000 mg/kg bw. Mortality, clinical observations and body weight were analyzed for 14 days after exposure. In day 14, necropsy was performed and all animals were subjected to a necropsy and a macroscopic examination. No effects on mortality, body weight and macroscopic findings were observed. Treatment caused decreased activity, hunched back and piloerection. Under the conditions of this study, the acute oral LD50 was determined to be greater than 2000 mg/kg bw in female rats.