Reaction mass of 1-[rac-(1R,6S)-2,2,6-trimethylcyclohexyl]pentan-3-ol isomer 1 and 1-[rac-(1S,6S)-2,2,6-trimethylcyclohexyl]pentan-3-ol

Endpoint summary

Description of key information

Acute oral toxicity

No mortality was observed at dosing level 2000 mg/kg. The LD50 of the test item was determined to be >5000 mg/kg.

Acute dermal toxicity

The acute dermal LD50 of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

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:

from 2000-05-17 to 2000-07-20

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl : CD ® (SD) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: males - 202 to 233 g; females - 209 to 226 g
- Fasting period before study: overnight fasting right before dosing
- Housing: in groups of three by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum during the study
- Water: ad libitum during the study
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

CLASS METHOD
- Rationale for the selection of the starting dose: based on available information. The testing sequence followed the flow chart described in OECD 423.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
-- observations: at 30 min, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days
-- weighing: prior to dosing and at 7 and 14 days after treatment
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathological examination, examination of major organs

Statistics:

No statistical analysis was performed. The LD50 was determined from the nominal dosing level.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Diarrhoea was noted in two male animals during the day of dosing. No other adverse clinical signs were noted.

Gross pathology:

No abnormalities were noted at necropsy.

Bodyweight and bodyweight gain during the treatment and observation period

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) during Week
		0	7	14	1	2
2000	1-0 Female 1-2 Female 1-3 Female	216 226 209	246 264 240	262 285 261	30 38 31	16 21 21
	2-0 Male 2-1 Male 2-3 Male	222 233 202	286 299 255	325 367 385	64 66 53	39 68 30

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality was observed at dosing level 2000 mg/kg. The LD50 of the test item was determined to be >5000 mg/kg.

Executive summary:

A study was performed to assess the acute oral toxicity of the test item following a single oral administration to the Sprague-Dawley CD strain rat. The test was performed according to OECD 423 "Acute Oral Toxicity - Acute Toxic Class Method" (1996) and Commission Directive 96/54/EC Method B1 tris. 2000 mg/kg bodyweight was selected as the starting dose. A group of three fasted females was treated with the starting dose. This was followed by a group of three fasted males at the same dose level. The test item was administered orally, undiluted. The animals were observed 30 min, 1, 2 and 4 hours after dosing and then once daily for fourteen days. Bodyweights were recorded on the day of dosing and on Days 7 and 14. At the end of the observation period all animals were killed by cervical dislocation and subjected to gross necropsy. There were no deaths during the study. Diarrhoea was noted in two male animals during the day of dosing after 2 and 4 hours. No other adverse clinical signs were noted. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute oral LD50 of the test item in the Sprague-Dawley rat, was estimated as being greater than 5000 mg/kg bodyweight as no mortalities were noted in animals treated with 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 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:

from 2000-06-05 to 2000-07-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl : CD® (SD) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: males - 201 to 207 g, females - 202 to 222 g
- Housing: in suspended polypropylene cages furnished with woodflake. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet: ad libitum during the study
- Water: ad libitum during the study
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: the back and flanks of each animal
- % coverage: 10 % of the total body surface area
- Type of wrap: surgical gauze
- On the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers.

REMOVAL OF TEST SUBSTANCE
- Washing: wiped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2.21 mL/kg

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: at 30 min, 1, 2 and 4 hours after dosing and sunsequesntly once daily for 14 days.
- Frequency of weighings: prior to application on day 0 and on day 7 and 14
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

- Dermal reactions: No signs of dermal irritation were noted during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

A study according OECD 402 (1987) and Commission Directive 92/69/EEC Method B.3 was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. A group of 10 animals (5 males and 5 females) was given a single 24-hour, semioccluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for 14 days after the day of treatment and were then killed for gross pathological examination. No death animals were observed during the study. No signs of systemic toxicity or dermal irritation were noted. All animals showed an expected gain in bodyweight during the study period. No abnormalities were noted at necropsy of the surviving animals. The acute dermal LD50 of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

A study was performed to assess the acute oral toxicity of the test item following a single oral administration to the Sprague-Dawley CD strain rat. The test was performed according to OECD 423 "Acute Oral Toxicity - Acute Toxic Class Method" (1996) and Commission Directive 96/54/EC Method B1 tris. 2000 mg/kg bodyweight was selected as the starting dose. A group of three fasted females was treated with the starting dose. This was followed by a group of three fasted males at the same dose level. The test item was administered orally, undiluted. The animals were observed 30 min, 1, 2 and 4 hours after dosing and then once daily for fourteen days. Bodyweights were recorded on the day of dosing and on Days 7 and 14. At the end of the observation period all animals were killed by cervical dislocation and subjected to gross necropsy. There were no deaths during the study. Diarrhoea was noted in two male animals during the day of dosing after 2 and 4 hours. No other adverse clinical signs were noted. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute oral LD50 of the test item in the Sprague-Dawley rat, was estimated as being greater than 5000 mg/kg bodyweight as no mortalities were noted in animals treated with 2000 mg/kg bodyweight.

Acute dermal toxicity

A study according OECD 402 (1987) and Commission Directive 92/69/EEC Method B.3 was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. A group of 10 animals (5 males and 5 females) was given a single 24-hour, semioccluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for 14 days after the day of treatment and were then killed for gross pathological examination. No death animals were observed during the study. No signs of systemic toxicity or dermal irritation were noted. All animals showed an expected gain in bodyweight during the study period. No abnormalities were noted at necropsy of the surviving animals. The acute dermal LD50 of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EC) No 2017/776.