Registration Dossier

Acute oral toxicity study (standard acute method): LD50 6176 mg/kg bw (rat)

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of 4 albino rats (2 male, 2 female) were administered the test material by gavage at doses of approx. 3, 4.5, 7 and 10 g/kg bw (25% w/v Diacid in corn oil). After treatment the animals were observed for 14 days for clinical signs. Body weights were measured at start and end of the observation period. Necropsy was performed on all animals.

GLP compliance:

no

Remarks:

study performed prior to GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ARS/Sprague-Dawley, Madison, Wisconsin.
- Age at study initiation: Young rats, no exact age available
- Weight at study initiation: 157-191 g
- Fasting period before study: 16 hours
- Housing: Stock cages
- Diet (e.g. ad libitum): Ad libitum, standard laboratory diet
- Water (e.g. ad libitum): Ad libitum, standard water
- Acclimation period: Five days under observation

ENVIRONMENTAL CONDITIONS
No data available

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% w/v
- Amount of vehicle (if gavage): varying per dose group (increased volume for higher dose)
- Justification for choice of vehicle: generally used vehicle
- Purity: No data available

Doses:

- 3,038 mg/kg bw
- 4,556 mg/kg bw
- 6,834 mg/kg bw
- 10,250 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations continuously, weights: initial and final (14 days)
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, necropsy of animals that died during the observation period

Statistics:

The acute oral median lethal dose (LD50) was calculated using interpolation methods described by Weil (1952), Thompson (1947) and Thompson and Weil (1952).

Preliminary study:

Not relevant

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 176 mg/kg bw

Based on:

test mat.

95% CL:

> 5 548.9 - <= 6 803.1

Remarks on result:

other: SD of LD50: +/- 627.1 mg/kg

Mortality:

No mortality occurred in the two test groups receiving the lowest doses. 3 out of 4 deaths and 4 out of 4 deaths occurred in the 6834 and 10250 mg/kg bw groups during the 14 day observation period, respectively. Deaths occurred within 3 days in all cases.

Clinical signs:

other: Hypoactivity, ruffed fur, labored breathing, muscular weakness and diuresis were noted throughout the test groups. Labored breathing was not noted in the low dose group, while muscular weakness and diuresis were only observed in the two highest dose group

Gross pathology:

Necropsy examination of the animals that died revealed gastroenteritis. No gross pathologic alterations were noted among the surviving animals.

Other findings:

No data available.

Clinical signs

Dose (mg/kg bw)	Reaction	Time of onset after dose administration	Duration of reaction
3038	Hypoactivity	1 hour	1 day
	Ruffed fur	1 hour	1 day
4556	Hypoactivity	1 hour	2 days
	Ruffed fur	1 hour	2 days
	Labored breathing	3 hours	6-22 hours
6834	Hypoactivity	1 hour	5 days
	Ruffed fur	1 hour	5 days
	Labored breathing	2 hours	2 days
	Muscular weakness	3 hours	2 days
	Diuresis	6-22 hours	2 days
10250	Hypoactivity	1 hour	Until death
	Ruffed fur	1 hour
	Labored breathing	2 hours
	Muscular weakness	3 hours
	Diuresis	6-22 hours

Body weights

Dose (mg/kg bw)	Animal	Body weight (grams)
		Initial	Final
3038	1-M	173	274
	2-M	157	258
	3-F	163	215
	4-F	164	220
4556	5-M	163	286
	6-M	168	286
	7-F	171	224
	8-F	190	226
6834	9-M	164	-
	10-M	163	277
	11-F	185	-
	12-F	183	-
10250	13-M	160	-
	14-M	174	-
	15-F	191	-
	16-F	176	-

Interpretation of results:

GHS criteria not met

Conclusions:

In this study the acute oral toxicity potential of Diacid 1550 was tested in rats by administration of doses varying from 3 to 10 g/kg bw by gavage. The acute oral LD50 was established to be 6176 mg/kg bw and therefore the substance is not considered acute toxic via the oral route and does not have to be classified in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.

Executive summary:

Groups of 4 albino rats (2 male, 2 female) were administered by gavage the test material at doses of approx. 3, 4.5, 7 and 10 g/kg bw (25% w/v Diacid in corn oil). After treatment the animals were observed for 14 days for clinical signs. Body weights were measured at start and end of the observation period. Necropsy was performed on all animals.

No mortality occurred in the two test groups receiving the lowest doses. 3 out of 4 deaths and 4 out of 4 deaths occurred in the 6834 and 10250 mg/kg bw groups during the 14 day observation period, respectively. Deaths occurred within 3 days in all cases. Hypoactivity, ruffed fur, labored breathing, muscular weakness and diuresis were noted throughout the test groups. Labored breathing was not noted in the low dose group, while muscular weakness and diuresis were only observed in the two highest dose groups. The increase in clinical signs was dose-related. Body weights of male and female animals were comparable throughout the groups at the start and end of the study. No statistical analysis was performed. Necropsy examination of the animals that died revealed gastroenteritis. No gross pathologic alterations were noted among the surviving animals.

The acute oral LD50 was established to be 6176 mg/kg bw and therefore the substance is not considered acute toxic via the oral route.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 176 mg/kg bw

Endpoint conclusion:

no study available

Endpoint conclusion:

no study available

Groups of 4 albino rats (2 male, 2 female) were administered by gavage the test material at doses of approx. 3, 4.5, 7 and 10 g/kg bw (25% w/v Diacid in corn oil). After treatment the animals were observed for 14 days for clinical signs. Body weights were measured at start and end of the observation period. Necropsy was performed on all animals.

No mortality occurred in the two test groups receiving the lowest doses. 3 out of 4 deaths and 4 out of 4 deaths occurred in the 6834 and 10250 mg/kg bw groups during the 14 day observation period, respectively. Deaths occurred within 3 days in all cases. Hypoactivity, ruffed fur, labored breathing, muscular weakness and diuresis were noted throughout the test groups. Labored breathing was not noted in the low dose group, while muscular weakness and diuresis were only observed in the two highest dose groups. The increase in clinical signs was dose-related. Body weights of male and female animals were comparable throughout the groups at the start and end of the study. No statistical analysis was performed. Necropsy examination of the animals that died revealed gastroenteritis. No gross pathologic alterations were noted among the surviving animals.

The acute oral LD50 was established to be 6176 mg/kg bw and therefore the substance is not considered acute toxic via the oral route.

Justification for selection of acute toxicity – oral endpoint
One study available which was performed similar to the OECD guidelines.

Based on the available information, Diacid 1550 does not have to be classified as acute toxic via the oral route in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.