Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant study, similar to test guideline OECD 401.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD 401
Deviations:
yes
Remarks:
(i.p. administration, 7-days observation period, no necropsies)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: 4,4'-dichlorodiphenylsulfone (DCDPS)
- Physical state: white powder
- Storage condition: at room temperature, protected from light
- Test item sample received on 02-Jan-1989

Test animals

Species:
mouse
Strain:
ICR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley Inc, Frederick, MD, USA
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: males 27-37 g, females 22-28 g
- Housing: in groups of max. 5 animals/cage, in autoclavable plastic cages with filter tops
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 74 ±6 °F (23.3 ± 3.4 °C)
- Humidity: 50 ± 20 %
- Photoperiod: 12 hours dark / 12 hours light

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
corn oil
Details on exposure:
Single intraperitoneal injection
Doses:
500, 1000, 1500, 2000, 2500 or 5000 mg/kg bw
No. of animals per sex per dose:
5 animals
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Weighing: once prior to dosing and on days 1 and 3
- Necropsy of survivors performed: no
Statistics:
Probit analysis

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 448 mg/kg bw
Based on:
test mat.
Mortality:
The mortality incidences noted in males (m) and females (f) during the 7-days observation period were as follows:
0/5 (m), 0/5 (f) in controls and at 500 and 1000 mg/kg bw
1/5 (m), 2/5 (f) at 1500 mg/kg bw
3/4 (m), 2/5 (f) at 2000 mg/kg bw
5/5 (m), 4/5 (f) at 2500 mg/kg bw
4/5 (m), 4/5 (f) at 5000 mg/kg bw
Clinical signs:
Head tilt, running in circles, lethargy, piloerection, hunched posture and/or cloudy eyes were noted at 1500 mg/kg bw and/or at higher dose levels.
Body weight:
In treated mice, dose-dependent decreases in body weight were noted as compared to pre-treatment body weights.
Gross pathology:
Not determined

Applicant's summary and conclusion

Executive summary:

This acute toxicity study (Microbiological Associates Inc., 1991) was performed as a preliminary test in order to set dose levels for a micronucleus test (see section 7.6.2).

Young adult ICR mice (5 mice/sex/dose level) were treated by intraperitoneal injection of DCDPS in corn oil at dose levels of 0 (vehicle control), 500, 1000, 1500, 2000, 2500 or 5000 mg/kg bw. Dose-dependant mortality was noted in both sexes at 1500 to 5000 mg/kg bw during the 7 -days observation period. Male and female animals treated at 1500 mg/kg bw or higher dose levels showed head tilt, running in circles, lethargy, piloerection, hunched posture and or cloudy eyes. Dose-dependent decreases in body weight were noted in treated mice as compared to pre-treatment body weights.

The LD50 value for the intraperitoneal route was 2448 mg/kg bw. Based on this LD50 value, DCDPS dislays low acute toxicity following intraperitoneal exposure.