NALCO 73280

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 May 2001 to 18 July 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted in accordance with International Guidelines and in accordance with the principles of Good Laboratory Practise (GLP).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): EH&S 01-114
- Lot/batch No.:XC1B1263A0

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals
-Source: Male and female Wistar rats were supplied by Ace Animals, Boyertown, PA, USA
-Weight at study initiation: 205-225g for males and 251- 267 g for females. The bodyweights fell within an interval of ± 20% of the mean initial bodyweight.
- Housing: The animals were housed 5/sex/cage in suspended wire cages. Bedding was placed beneath the cages and changed at least 3 times / week
- Fresh Purina rat chow (diet #5012) was freely available except for 16 - 20 hours prior to dosing.
- Water (e.g. ad libitum): free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- The animal room was reserved exclusively for rats on acute tests, was temperature controlled, had a 12hour light/dark cycle, and was clean and vermin free.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Dose level: 2000mg/kg. The test substance was used as received.

No. of animals per sex per dose:

5 Females at 2000mg/kg
5 Males at 2000mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for toxicity and pharmacological effects 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. The animals were obserevd twice daily for mortality.Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment, at death and at termination in the survivors..
- Necropsy of survivors performed: yes

Statistics:

An estimate of the LD50 was made based on the results

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All animals survived the 2000mg/kg oral dose

Mortality:

There were no deaths.

Clinical signs:

other: 4 males had red staining around the mouth and nose post dosing, two of these also had additional signs of either wetmess of the anogenital area or Dyspnea and diarrhea 2 females had red staining around the mouth and nose post dosing. Individual clinical o

Gross pathology:

Necropsy results were normal in all animals.
Individual necropsy observations are given in table 3

Other findings:

None

Any other information on results incl. tables

Table 1 Clinical signs

Time Period	Animal n.o and sex
	1M	2M	3M	4M	5M	6F	7F	8F	9F	10F
1 hour post dose	R		1	M, 1	1			1		1
2 hour post dose	R, 1			M
4 hour post dose	R			D
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14

1 = Nose / mouth area stained red

R = Wetness of anogenital area

D = Diarrhoea

M = Dyspnea

No entry indicates animal appeared normal at that observation period.

Table 2 Individual bodyweights (g)

Animal n.o and sex	Dose volume (ml)	Day 0	Day 7	Day 14
1M	0.32	217	294	337
2M	0.33	224	300	332
3M	0.33	225	317	375
4M	0.32	219	287	328
5M	0.30	206	300	349
Mean 218 300 344 SD 7.6 11.1 18.9 n 5 5 5
6F	0.37	253	290	303
7F	0.40	267	304	319
8F	0.38	256	294	303
9F	0.37	251	284	286
10F	0.38	255	284	290
Mean 256 291 300 SD 6.2 8.3 13.0 n 5 5 5

Table 3 Necropsy observations

Observation	1M	2M	3M	4M	5M	6F	7F	8F	9F	10F
Death / Sacrifice	S	S	S	S	S	S	S	S	S	S
Normal	X	X	X	X	X	X	X	X	X	X

S= Sacrifice

X=Observed

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 of the test substance in male and female Wistar rats is >2000 mg/kg bodyweight

Executive summary:

The study was performed to determine the potential for toxicity of the test substance when administered orally. The study was designed to comply with OECD guideline n.o 401 "Acute Oral Toxicity".

Method

Five healthy male and five healthy female Wistar rats were dosed orally with the test substance at 2000 mg/kg bodyweight. The rats were observed 1, 2, and 4 hours post dose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Bodyweights were recorded immediately pre-test, weekly, at death and at termination in survivors.

Results

Mortality - There were no deaths

Clinical signs - Abnormal physical signs of wetness of the anogenital area, dyspnea, diarrhoea, and nose/mouth area stained red were noted in some animals.

Bodyweight - Bodyweight changes were normal in all animals.

Necropsy - No abnormalities were noted.

Conclusion - The oral LD50 of the test substance in male and female Wistar rats is >2000 mg/kg bodyweight