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Toxicological information

Acute Toxicity: oral

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: suspension
Details on test material:
- Name of test material (as cited in study report): Diacid 1550
- Physical state: No data available
- Analytical purity: No data available
- Lot/batch No.: Confidential information
- Expiration date of the lot/batch: No data available

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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

Administration / exposure

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).

Results and discussion

Preliminary study:
Not relevant
Effect levels
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:
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 weight:
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.
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.

Any other information on results incl. tables

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 -

Applicant's summary and conclusion

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.