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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:
22 February 1985 to 09 April 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
test according to OECD 401 under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
12 May 1981
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Central Institute for Breeding of Laboratory Animals TNO (CPB), Zeist, The Netherlands
- Females (if applicable) nulliparous and non-pregnant: no data
- Age at study initiation: no data
- Weight at study initiation: males 176-250 g; females 123-156 g
- Fasting period before study: yes (overnight until 2-4.5 hours after dosing)
- Housing: individually in macrolon cages
- Diet: standard pelleted lab feed (RMH, Hope Farms) ad libitum
- Water: tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 °C
- Humidity (%): 50-65%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE: propylene glycol

MAXIMUM DOSE VOLUME APPLIED: not indicated

DOSAGE PREPARATION (if unusual): sonicated for 3 hours (suspension)

Rationale for the selection of the doses: pre-test in 1 male/1 female per group at 13, 18, 24 and 32 mg/kg bw --> no deaths
additional pre-test in 1 male/1 female per group at 1300, 2400 and 3200 (male only) --> all dead within 4 days.
Doses:
1100, 1500 and 2000 mg/kg bw
No. of animals per sex per dose:
5 males + 5 females per group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: once daily for mortality and clinical signs
- Frequency of weighing: on day 0, 7 and 14
- Necropsy of survivors performed: yes
Statistics:
LD50 value according to Finney (1971)

Results and discussion

Preliminary study:
pre-test in 1 male/1 female per group at 13, 18, 24 and 32 mg/kg bw --> no deaths
additional pre-test in 1 male/1 female per group at 1300, 2400 and 3200 (male only) --> all dead within 4 days.
Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 400 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 200 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
Based on:
test mat.
Mortality:
1100 mg/kg bw: 2 males and 2 females (before day 6)
1500 mg/kg bw: 2 males and 4 females (before day 6)
2000 mg/kg bw: 4 males and 5 females (before day 6)
Clinical signs:
apathy and lethargy during the initial days
Body weight:
decreased in animals that died
Gross pathology:
in animals that died: diminution of antrum (sometimes with enlarged forestoach and petechiae in 5 animals; no abnormalities in others
in survivors: yellow granules in the stomach (2 animals); whitish material in the bladder (3 animals); no abnormalities in others

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 is 1300 mg/kg bw
Executive summary:

Five rats per sex received a single dose of 1100, 1500 or 2000 mg/kg bw by gavage. During the 14 day observation period 4, 6 and 9 animals died at 1100, 1500 and 2000 mg/kg respectively. These animals showed decreased body weight, apathy and letargy and effects on the antrum. Other animals survived and showed no clear treatment related effects.

Based on these findings it is concluded that the LD50 is 1300 mg/kg bw (males and females combined).