3,20-bis(ethylenedioxy)pregna-5,7-diene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-05-14 to 1991-05-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study carried out under GLP and EU method B3

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

3,20-bis(ethylenedioxy)pregna-5,7-diene

EC Number:

243-175-0

EC Name:

3,20-bis(ethylenedioxy)pregna-5,7-diene

Cas Number:

19592-55-3

Molecular formula:

C25H36O4

IUPAC Name:

(1S,3aR,9aR,9bS,11aS)-9a,11a-dimethyl-1-(2-methyl-1,3-dioxolan-2-yl)-1,2,3,3a,6,8,9,9a,9b,10,11,11a-dodecahydrospiro[cyclopenta[a]phenanthrene-7,2'-[1,3]dioxolane]

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Proketal
- Physical state: Solid powder
-

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/CPB, Zeist, The Netherlands
- Weight at study initiation: Males: 175g to 200g, females: 150g-175g
- Housing: The rats were housed continuously in Macrolon cages containing sawdust, with two or three animals per cage, except for the application period of 24 hours; then the rats were housed singly.
- Diet (e.g. ad libitum): RHM-TM, Hope Farms, Woerden, The Netherlands
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 40-60%
- Air changes (per hr): 16
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: Tragacant mucilage 1.25% in distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Wiped
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg
- Concentration (if solution): 6.4ml/kg
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

1

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0, 0.5, 1.5, 3 and 24 hours
- Necropsy of survivors performed: no

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

During the application period, when the rats were wearing collars, chromodacryorrhoea and dirty noses were noticed in males and females. The production of red tears is a normal physiological phenomenon, but is not always noticed due to grooming. In the present study normal grooming behaviour was hindered during the application period by the collars fitted around the neck of the rats. Therefore, chromodacryrrhoea and dirty noses are not considered to be treatment-related signs. No other clinical signs were observed.

Body weight:

 Male and female rats gained normal weights one day prior to dosing. Upon exposure to a single dermal dose of 2000 mg/kg of proketal females but not males lost some weight during the first few days after treatment. Thereafter, normal growth was observed in males, but weight-gains of females were relatively low during the second week of the study (see table below).
 

Other findings:

During the application period, chromodacryorrhea and dirty noses were noticed from 0-0. 5 hours after the start of the treatment up to 24 hours after administration in both males and females. Upon removal of the collars and patches, these signs disappeared. No further symptoms were observed.

Any other information on results incl. tables

Sex	Dose	Animalnumber	1daybeforedosing	Dayofdosing	2  daysafterdosing	7daysafterdosing	14daysafterdosing
	(mg/kg)
M	2000	1	200	204	204	223	251
		2	211	220	220	244	265
		3	197	204	210	222	241
		4	197	198	209	230	255
		5	190	195	198	219	251
		Mean	199.0	204.2	208.2	227.6	252.6
F	2000	1	166	171	160	168	164
		2	145	150	145	150	154
		3	153	160	153	159	165
		4	162	167	170	175	184
		5	157	159	158	167	168

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Acute dermal LD50 is greater than 2000 mg/kg in both male and female rats.

Executive summary:

.