19-Norpregn-5(10)-ene-21-nitrile, 17-hydroxy-3-oxo-, (17.alpha.)-

Endpoint summary

Description of key information

LD50 oral (rat): > 2000 mg/kg bw [Kurth 2007]
LD50 dermal (rat): > 2000 mg/kg bw [Kurth 2009a]

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug to Nov 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 December 2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Weight at study initiation: males: 104 - 109 g; females: 105 – 112 g
- Fasting period before study: 17.5 - 18.5 h
- Housing: individually in conventional cages
- Diet (e.g. ad libitum): pell. Ssniff ® R / M - H; ad libitum, 24 hours per day
- Water (e.g. ad libitum): filtrated tap water; ad libitum, 24 hours per day
- Acclimation period: ≥ 7 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 55-60
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 2.0 mg carboxymethyl cellulose ad 1.0 mL Aqua dest.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD
acute toxic class
- Rationale for the selection of the starting dose: Limit dose

Doses:

2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days
- Frequency of observations and weighing: All alterations of the baseline condition of the animals were recorded. All animals were checked four times on administration day and once daily on the following days up to day 21 of the test. Body weight was determined at the start (day 1), on day 8 and day 15 and at the end of the study (day 21).
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed.

Clinical signs:

other: No clinical signs observed.

Gross pathology:

No adverse findings observed.

No animal died in the course of the study. A single oral (gavage) application of 2000 mg/kg was tolerated without compound-related clinical findings. The body weight gain on days 8, 15 and 21 was within the normal range for rats of this age and strain, which are routinely used in the laboratory. Autopsy revealed no compound-related findings.

Conclusions:

A single oral administration of the test substance by gavage to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, clinical signs, effects on body weight gain and gross pathological findings. According to OECD TG 423 the oral LD50 of the test item is therefore > 2000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study according to OECD TG 423 (adopted 17 December 2001), groups (3/sex) of Wistar rats, were given a single oral dose of 5-Dehydrocyanomethylketon in 2.0 mg carboxymethyl cellulose ad 1.0 mL Aqua dest. at a dose of 2000 mg/kg bw.  Animals were then observed for 21 days.

 

Oral LD50 Combined ≥ 2000 mg/kg  bw

No mortality occurred during the conduction of this limit test.

Formulation is of low Toxicity based on the LD50 in males and females. The test item does not need to be classified with regard to acute oral toxicity.

There were no treatment related clinical signs, necropsy findings or changes in body weight.)

This acute oral study is classified as acceptable.  It does satisfy the guideline requirement for an acute oral study OECD 423 in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July to Nov 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

Deviations:

yes

Remarks:

- 3 instead of 5 animals/sex used

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Weight at study initiation: males: 283 – 290 g; females: 208 – 218 g
- Housing: individually in conventional cages
- Diet (e.g. ad libitum): pell. Ssniff® R / M - H, ad libitum, 24 hours per day
- Water (e.g. ad libitum): filtrated tap water, ad libitum, 24 hours per day
- Acclimation period: ≥ 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 56-59
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

physiological saline

Details on dermal exposure:

TEST SITE
- Area of exposure: The backs of the animals, the paste was administered on a piece of gauze the size of 4 x 9 cm
- % coverage: approximately 10% of the body surface area of a rat
- Type of wrap if used: not reported; occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: Substance residues were removed with warm water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a paste consisting of the original compound [males: 566-580 mg ad 0.40 resp. 0.45 mL 0.9% (w/v) sodium chloride; females: 416.7-436.3 mg ad 0.30 mL 0.9% (w/v) sodium chloride]
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): see above
- Concentration (if solution): see above

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21days
- Frequency of observations and weighing: All alterations of the baseline condition of the animals were recorded. All animals were checked four times on administration day and once daily on the following days up to day 21 of the test. All alterations of the skin at the administration sites of all animals were recorded according to the scoring system recommended by the EU. The application sites were evaluated 1, 24, 48 and 72 h after removal of the patches. Body weight was determined at the start (day 1), on days 8 and 15 and at the end of the study (day 21).
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: test substance (technical quality including impurities)

Mortality:

No mortality was observed.

Clinical signs:

other: After administration of 2000 mg/kg of the test chemical focal to total hairless areas were found in one male animal (both fore- and hind limbs, inguinal region, abdomen) from day 15 onwards and in one female animal (both hind limbs, abdomen) on day 13 to

Gross pathology:

Autopsy revealed no compound-related findings, because the observed lesions (scab formation) in the skin are considered to be not substance related.

Conclusions:

A single dermal administration of the test substance (technical quality including impurities) to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities and gross pathological findings. After administration of 2000 mg/kg the test item single animals showed hairless areas and thinning fur in the course of the study. These findings are suspected to be compound-related because they are known findings in rats after treatment with hormones. Additionally, a slight decrease in body weight was observed in some animals on day 8. This effect was reversible on day 15 of the test.

According to OECD TG 402 the dermal LD50 of the test item is therefore > 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study according to OECD TG 402 (adopted 17 December 1987), groups of young adult Wistar rats (3/sex) were dermally exposed to 5-Dehydrocyanomethylketon in physiological saline for 24 hours at a dose of 2000 mg/kg bw.  Animals then were observed for 21 days.

Dermal LD50 Combined = 2000 mg/kg bw

No mortality occurred during the conduction of this limit test.

Dehydrocyanomethylketon is of low Toxicity based on the LD50 males and females.

After administration of 2000 mg/kg the test item single animals showed hairless areas and thinning fur in the course of the study. These findings are suspected to be compound-related because they are known findings in rats after treatment with hormones. Additionally, a slight decrease in body weight was observed in some animals on day 8. This effect was reversible on day 15 of the test.

No other effects were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

In an acute oral toxicity study according to OECD TG 423 (adopted 17 December 2001), groups (3/sex) of Wistar rats, were given a single oral dose of 5-Dehydrocyanomethylketon in 2.0 mg carboxymethyl cellulose ad 1.0 mL Aqua dest. at a dose of 2000 mg/kg bw.  Animals were then observed for 21 days.

Oral LD50 Combined ≥ 2000 mg/kg  bw

No mortality occurred during the conduction of this limit test.

Formulation is of low Toxicity based on the LD50 in males and females. The test item does not need to be classified with regard to acute oral toxicity.

There were no treatment related clinical signs, necropsy findings or changes in body weight.)

This acute oral study is classified as acceptable.  It does satisfy the guideline requirement for an acute oral study OECD 423 in the rat.

 

In an acute dermal toxicity study according to OECD TG 402 (adopted 17 December 1987), groups of young adult Wistar rats (3/sex) were dermally exposed to 5-Dehydrocyanomethylketon in physiological saline for 24 hours at a dose of 2000 mg/kg bw.  Animals then were observed for 21 days.

Dermal LD50 Combined = 2000 mg/kg bw

No mortality occurred during the conduction of this limit test.

Dehydrocyanomethylketon is of low Toxicity based on the LD50 males and females.

After administration of 2000 mg/kg the test item single animals showed hairless areas and thinning fur in the course of the study. These findings are suspected to be compound-related because they are known findings in rats after treatment with hormones. Additionally, a slight decrease in body weight was observed in some animals on day 8. This effect was reversible on day 15 of the test.

No other effects were observed.

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.