Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study, well documented with accepted restrictions (no GLP).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Principles of method if other than guideline:
BASF-Test
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): omega-chlor-para-fluoracetophenon [German]
- Physical state: aqueous solution
- Analytical purity: 98 %, technical grade

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Age at study initiation: no data
- Weight at study initiation: mean weights: males 189.25 g, females 181.25 g (animals of comparable weight: ± 20 % of the mean weight)
- Fasting period before study: 16 hours before administration
- Housing: 5/cage
- Diet: Kliba Labordiaet 343, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 wk


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4.64, 2.15, 1.00, 0.464 % (w/v)
- Amount of vehicle (if gavage): 10 ml
- Justification for choice of vehicle: aqueous formulation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 464.0 mg/kg bw
Doses:
464.0, 215.0, 100.0, 46.4 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: recording of signs and symptoms severeal times on the day of administration, at least once each workday; check for moribund and dead animals twice each workday and once on holidays; weighing on day 7 and day 13
- Necropsy of survivors performed: yes, gross-pathological examination
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 248 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 215 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
> 215 - < 464 mg/kg bw
Mortality:
464 mg/kg bw:
Males and females: 5/5 each after 1 d

215 mg/kg bw:
Males: 0/5
Females: 3/5 after 1 d

100 mg/kg bw:
Males: 0/5
Females: 1/5 after 14 d (probably not due to test substance, therefore not considered for LD50 determination)

46.4 mg/kg bw:
Males and females: 0/5 each
Clinical signs:
464 mg/kg:
Males and females: dyspnea, apathy, staggering, piloerection, diarrhea, poor general state

215 mg/kg bw:
males and females: dyspnea, apathy, piloerection, impaired general state, poor general state

100 mg/kg bw:
Males: piloerection
Females: dyspnea, apathy, piloerection, impaired general state, poor general state

46.4 mg/kg bw:
Males and females: no symptoms observed
Body weight:
See table.
Gross pathology:
Deceased animals (male and female):
General congestion; glandular stomach: reddened mucosa
One female of the 100 mg/kg bw group: perforation of stomach with fibrinous peritonitis

Sacrificed animals (male and female):
46.4 mg/kg bw: no pathological findings noted.
100 mg/kg bw: forestomach: thickening of the wall.
215 mg/kg bw: forestomach: thickening of the wall, intraabdominal adhesions.

Any other information on results incl. tables

Mean body weights (g):

Males:

            Dose (mg/kg bw)
 Time  464.0  215.0  100.0  46.4
 Beginning  196  190  189  182
 7 d  -  237  251  259
 13 d  -  273  282  291

Females:

            Dose (mg/kg bw)
 Time  464.0  215.0  100.0  46.4
 Beginning  180  180  178  187
 7 d  -  211  208  226
 13 d  -  222  222  239

Applicant's summary and conclusion