3,3-[(2,2-dimethylpropane-1,3-diyl)bis(oxy)]-17α-hydroxyestr-5(10)-ene-17-carbonitrile

Endpoint summary

Description of key information

LD50 oral (rat): > 2000 mg/kg bw [Draft report, Lewin 2001a]
LD50 dermal (rat): > 2000 mg/kg bw [Draft report, Lewin 2001b]

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:

other information

Study period:

Sep to Nov 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: 0.9 % NaCl + 0.085 % Myrj 53 in bidist. water

Doses:

200 and 2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

No animal died in the course of the study. After single oral application of 200 or 2000 mg/kg no clinical findings were observed in male and female animals. The body weight gain on days 7 and 14 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.

Executive summary:

A single oral administration of the test substance by gavage to male and female rats at 200 and 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 ZK 30367 is therefore > 2000 mg/kg body weight.

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:

other information

Study period:

Oct 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

- 3 instead of 5 animals/sex used

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

paraffin oil

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

No animal died in the course of the study.

At 2000 mg/kg an encrusted, reddened nose was observed in the three male and in one of the three female animals at 3 hours after substance administration.

One female animal did not gain body weight during the entire study period. As all other animals did not show this effect, the significance of the finding remains unclear.

Autopsy revealed no compound-related findings.

Executive summary:

A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, effects on body weight gain and gross pathological findings. Clinical signs (encrusted, reddened nose) were observed 3 hours after administration in both genders. According to OECD TG 402 the dermal LD50 of ZK 30367 is therefore > 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

The acute oral toxicity of the test substance was low with a LD50 value exceeding 2000 mg/kg bw in rats according to OECD TG 423 (Lewin, 2001a). At the limit-dose 2000 mg/kg no animal died and no effects on body weight gain or gross pathological findings were observed during the 14-day post observation period. At 2000 mg/kg slight apathy was observed in male animals during the first post observation day.

The acute dermal toxicity of the test substance was low with a LD50 value exceeding 2000 mg/kg bw in rats according to OECD TG 402 (Lewin, 2001b). At the limit-dose 2000 mg/kg no animal died and no effects on body weight gain or gross pathological findings were observed during the 14-day post observation period. Clinical signs (encrusted, reddened nose) were observed 3 hours after administration in both genders

Justification for selection of acute toxicity – oral endpoint
Only one reliability 1 study available

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP) is not required.