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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:
6 March - 20 March 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adults
- Weight at study initiation: 100-157 g (males), 112- 156 g (females)
- Fasting period before study: overnight before administration of test material
- Housing: The rats were housed in groups of five, males and females separated, in stainless steel cages with wire screen bottom and front.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2
- Humidity (%): 40-60
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 g/ 100 ml


MAXIMUM DOSE VOLUME APPLIED: 11.52 ml/kg

Doses:
3335, 4000, 4800, 5760 mg/kg (as a 50% w/v dilution in maize oil)
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: After treatment, the rats were observed frequently for signs of intoxication during the first 4 hours and thereafter at least once daily throughout the observation period. Individual body weights were recorded on day 0, 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 659 mg/kg bw
95% CL:
> 3 995 - < 5 433
Mortality:
3335 mg/kg dose; deaths 1/5 males, 1/5 females
4000 mg/kg dose; deaths 2/5 males, 1/5 females
4800 mg/kg dose; deaths 1/5 males, 4/5 females
5760 mg/kg dose; deaths 4/5 males; 4/5 females

Deaths occurred between 5 hours and 7 days after dosing.
Clinical signs:
During the first few hours after treatment, none of the rats showed any sign of intoxication. Later on, sluggishness, piloerection and coma were frequently observed.
Body weight:
The individual body weights on day 7 and 14 revealed growth retardation or weight loss in some rats, especially in the first post-treatment week.
Gross pathology:
Macroscopic examination at autopsy of the rats that died after dosing with 9.6 ml/kg and 11.52 ml/kg revealed a food overfilled stomach and empty intestines. The liver and kidneys in these rats showed pale discolouration. Pale discolouration of the kidneys was also found in some rats of these dose groups that survived the observation period. At autopsy of the survivors of the 6.67 and 8 ml/kg dose group, no treatment-related gross alterations were seen, at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
An acute oral toxicity LD50 value of >4659 mg/kg bw was reported in a reliable study carried out according to an appropriate OECD Guideline and in compliance with GLP.