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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:
1987-05-04, 1987-06-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981)
Deviations:
yes
Remarks:
(Animals were sacrificed at day 18 instead of day 14. Only 2 doses were examined instead of at least 3.)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Substance type: Organic
- Physical state: Solid
- Analytical purity: Lab. sample
- Lot/batch No.: WR 629
- Expiration date of the lot/batch: 1990-02
- Storage condition of test material: Room temperature, in the dark
- Other: Insoluble in water

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain as stated in the report: Tif: RAIf (SPF) hybrids of RII 1/Tif x RII 2/Tif
- Source: CIBA-GEIGY Ltd., Tierfarm, Sisseln, Switzerland
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 173 - 230 g
- Fasting period: Overnight before application
- Housing: Groups of 5 in Macrolon cages type 4 with standardised soft wood bedding (Societe Parisienne des sciures, Pantin)
- Diet: Ad libitum, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland)
- Water: Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): appr. 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: carboxymethylcellulose and polysorbate 80
Details on oral exposure:
VEHICLE
- Amount of vehicle: 0.5 % carboxymethylcellulose and 0.1 % polysorbate 80 in distilled water

MAXIMUM DOSE VOLUME APPLIED
- 10 mL / kg body weight for the lower and 20 mL/kg body weight for the higher dose (due to low solubility of test substance, further details see additional informations)
Doses:
oral single application of 2000 and 5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality, signs and symptoms daily. Body weight at start, on day 7, and on day 14
- Necropsy of survivors performed: yes; The animals were sacrificed for necropsy on day 18 instead day 14 because of legal holidays.
Statistics:
From the body weights, the group means and their standard deviations were calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
None
Clinical signs:
Clinical signs were dyspnea, exophthalmus, ruffled fur and curved body position. All findings resolved by day 11 and were no longer observed at the end of the recovery period.
Body weight:
Body weight gain was not affected.
Gross pathology:
No deviations from normal morphology were found.
Other findings:
None

Any other information on results incl. tables

Table 1. Signs and symptoms*

Cbservations Exposure day: hours Days of post-exposure period
1 2 3 5 1 2 3 4 5 6 7 8 9 10 11 12 13 >13
2000 mg/kg bw
dyspnea XX XX XX XX X X X X X X X X X




exophthalmos X X X X X X X X X X







ruffled fur X X X X X X X X X X X X X X



body position- curved X X X X X X











5000 mg/kg bw
dyspnea X X X XX X X X X X X







exophthalmos X X X X X X











ruffled fur X X X X X X X X X X X X X X



body position- curved X X X X X X X










* X = slight; XX = moderate; XXX = marked

Table 2. Body weights and standard deviations.

Dose mg/kg Males Females
Day 1 Day 7 Day 14 Day 1 Day 7 Day 14
2000 193/ 4.4 260/ 8.8 312/ 9.8 175/ 2.2 209/ 3.0 224/ 4.8
5000 223/ 4.8 272/10.8 328/ 8.0 196/ 6.3 219/ 3.7 230/ 9.9

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test, the acute oral LD50 of the test material to rats was found to be >5000 mg/kg bw.
Executive summary:

In this guideline (OECD 401) study conducted to GLP standards, the test material (EC 404-360-3) was determined to be practically nontoxic, with an acute oral LD50 > 5000 mg/kg bw. The test was conducted on male/female rats, administered by oral gavage with a vehicle of 0.5 % carboxymethylcellulose and 0.1 % polysorbate 80 in distilled water, at two different concentrations (2000 mg/kg bw and 5000 mg/kg bw). No mortality was observed, thus the test material is not classified as acutely toxic (oral) under CLP regulation 1272/2008.