(2E)-2-ethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-en-1-ol

Endpoint summary

Description of key information

Two oral acute toxicity studies are available showing LD50 > 2000 mg/kg bw.
One dermal acute toxicity study is available showing LD50 > 4600 mg/kg bw.

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:

1998-05-26 to 1998-06-09

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study following OECD guideline 401 but there was no certificate of analysis, no details about test substance and environmental conditions for animals

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no certificate of analysis, no details about test substance and environmental conditions

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: IFFA-CREDO, L'Arbresle, France
- Age at study initiation: about 6 weeks old
- Weight at study initiation: 188 - 210 g for males, 173 - 181 g for females
- Fasting period before study: overnight
- Housing: 5/sex in polypropylene cages
- Diet (e.g. ad libitum): pelleted diet (UAR A04-10, Epinay sur Orge, France ), ad libitum
- Acclimation period: at least 5 days

IN-LIFE DATES: From: 1998-05-26 To: 1998-06-09

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: observed daily for clinical signs; bodyweights recorded prior to the test material administration (D1), D4, D8 and D15
- Necropsy of survivors performed: yes

Statistics:

No data

Preliminary study:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: Six hours following administration of the test substance, a slight piloerection was observed in all animals. 1 hour after administration, a decrease in motor activity and muscle tone was noticed in one male and one female.

Gross pathology:

There were no visible organic or tissular lesions 14 days after treatment.

Other findings:

No data

Table 1: BODY WEIGHT - Individual values (g)

Animal N°	D1	D4	D8	D15	D15 – D1
Sex : Male
9315	192.6	215.4	276.0	338.2	145.6
9316	192.8	207.3	263.7	323.0	130.2
9317	209.3	255.5	300.4	357.5	148.2
9318	188.9	224.1	268.6	329.7	140.8
9319	201.2	238.5	276.7	333.2	132.0
Mean	197.0	228.2	277.1	336.3	139.4
SD	8.2	19.2	14.1	13.1	8.0
Sex : Female
9320	178.1	206.6	226.0	247.7	69.6
9321	180.5	211.4	227.2	245.5	65.0
9322	176.0	195.3	214.3	234.0	58.0
9323	173.2	198.9	220.7	237.1	63.9
9324	178.9	199.8	220.9	247.9	69.0
Mean	177.3	202.4	221.8	242.4	65.1
SD	2.8	6.5	5.1	6.5	4.7

MACROSCOPIC EXAMINATION

Sex : Male

Animal N°	MORTALITY		OBSERVATIONS
	Day	Cause
9315	D15	Sacrifice	Normal
9316	D15	Sacrifice	Normal
9317	D15	Sacrifice	Normal
9318	D15	Sacrifice	Normal
9319	D15	Sacrifice	Normal
Sex : Female
Animal N°	MORTALITY		OBSERVATIONS
	Day	Cause
9320	D15	Sacrifice	Normal
9321	D15	Sacrifice	Normal
9322	D15	Sacrifice	Normal
9323	D15	Sacrifice	Normal
9324	D15	Sacrifice	Normal

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Oral LD50 of the test substance is higher than 2000 mg/kg bw.
The substance is not classified according to directive 67/548/EEC and CLP regulation (EC) n° 1272/2008.

Executive summary:

An acute oral toxicity study (limit test) with the test item was conducted in 10 albino Sprague Dawley rats (5/sex/dose) under GLP conditions following OECD guideline 401. The test substance was administered through oral gavage at the single dose of 2000 mg/kg bw. Animals were observed daily for clinical signs and mortality for 14 days. Body weights were taken prior to the administration of the test material, D4, D8 and D15. Six hours following administration of the test substance, a slight piloerection was observed in all animals. 1 hour after administration, a decrease in motor activity and muscle tone was noticed in one male and one female. There was no mortality. All animals were subjected to necropsy at the end of the observation period. No gross lesions were found.

Therefore, oral LD50 of the test substance is higher than 2000 mg/kg bw. According to directive 67/548/EEC and CLP regulation (EC) n° 1272/2008, the test substance should not be classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP studies following OECD guideline 401 with minor deviations, considered as appropriate and reliable to complete this endpoint.

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:

From December 9 to 24, 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study conducted similarly to OECD Guideline 402 with minor deviations: no data about purity and no certificate of analysis of the test substance; no data on humidity and temperature, female animals bodyweight < 200 g at study initiation

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

no data about purity and no certificate of analysis of the test substance; no data on humidity and temperature; female animals bodyweight at study initiation < 200 g

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tac:N(SD)fBR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Taconic Farms, Inc., Germantown, USA
- Age at study initiation: 6 weeks
- Weight at study initiation: Males: 249-291 g; females: 167-191 g
- Housing: Individually housed in stainless steel cages with wire mesh floors and automatic watering devices
- Diet (e.g. ad libitum): Purina Lab Chow, ad libitum
- Water (e.g. ad libitum): Filtered tap water, ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Air changes: 14/hour
- Photoperiod: 12 hours dark / 12 hours light

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Intrascapular region
- % coverage: 30% of the body surface
- Type of wrap if used: Test sites were not wrapped; appropriate test substance was applied by syringe and gentle inunction to the clipped area and allowed to remain in contact with the skin and open air

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were not wiped after 24 hours because no excess test article was present.

Duration of exposure:

24 hours

Doses:

5 mL/kg bw

No. of animals per sex per dose:

Five

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed frequently for mortality, morbidity and overt toxic signs for the first 5 hours after dosing and twice daily thereafter for 14 days. Body weights were obtained on Days 0 and 14.
- Necropsy of survivors performed: Yes; surviving animals were sacrificed and examined grossly

Statistics:

No data

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 mL/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: - Clinical signs included lacrimation, diarrhea, crusty material on eyes and nose, desquamation, urine soaked fur, aggressiveness, vocalisation when touched, sore on back, and red appearance of the skin. - No important differences in the incidence and/or

Gross pathology:

Findings at gross necropsy were few (yellow rectangular firm area (lobes adhered) on liver of one male) and did not reveal any test material-related trends.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the acute dermal LD50 of the test item was higher than 5 mL/kg bw therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.

Executive summary:

In an acute dermal toxicity study performed similarly to OECD guideline 402 in compliance with GLP, a group of Tac:N(SD)fBR rats (5/sex) received a single dermal dose of the test item at 5 mL/kg on clipped area of intrascapular region representing 30% of the total body surface area. The application was allowed to remain in contact with the skin and open air for 24 hours. Parameters evaluated included survival, clinical observations, bodyweight gain and necropsy findings in all animals after a 14 days observation period. No mortality was observed. All animals showed expected gain in bodyweight. Clinical signs included lacrimation, diarrhea, crusty material on eyes and nose, desquamation, urine soaked fur, aggressiveness, vocalisation when touched, sore on back, and red appearance of the skin. No important differences in the incidence and/or nature of clinical signs between sexes were found. Findings at gross necropsy were few (yellow rectangular firm area (lobes adhered) on liver of one male) and did not reveal any test material-related trends. The acute dermal LD50 was higher than 5 mL/kg bw therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 600 mg/kg bw

Quality of whole database:

LP study conducted similarly to OECD Guideline 402 with minor deviations, considered as appropriate and reliable to complete this endpoint.

Additional information

In a GLP acute oral toxicity study (limit test) performed according to OECD guideline 401, no mortality and no clinical signs related to treatment were observed, therefore LD₅₀ was higher than 2000 mg/kg bw.

In an older study, also performed according to OECD guideline 401, the test item tested at 5000 mg/kg bw led to the following clinical signs without death: pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), diarrhea and increased salivation. LD₅₀ was higher than 5000 mg/kg bw.

In an acute dermal toxicity study (limit test), no mortality was observed in rats exposed to 5 mL/kg bw (corresponding to 4.6 g/kg bw).

Justification for selection of acute toxicity – oral endpoint
GLP study following OECD guideline 401.

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

Justification for classification or non-classification

As LD₅₀ for oral and dermal acute toxicity are higher than 2000 mg/kg bw, the test item is not classified according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.