Reaction mass of 2-(cis-4-methylcyclohexyl)propan-2-ol and 2-(trans-4-methylcyclohexyl)propan-2-ol and cis-1-methyl-4-(propan-2-yl)cyclohexanol and trans-1-methyl-4-(propan-2-yl)cyclohexanol

Endpoint summary

Description of key information

The oral LD50 for dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in female rats.

The acute dermal LD50 of dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in rats.

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:

04-19 February 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 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

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

13 September 2013

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Janvier Labs, Le Genest-St Isle, France.
- Age at study initiation: 9 weeks
- Weight at study initiation: 207-223 g
- Fasting period before study: Food was removed on Day 1 and then redistributed 4 h after administration of the test item.
- Housing: Animals were housed by group of three in solid bottomed clear polycarbonate cages with stainless steel mesh lid.
- Diet: Foodstuff (SAFE, A04), ad libitum
- Water: Drinking water (tap water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: Approximately 13 changes/h
- Photoperiod: 12 h dark / 12 h light

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.20 mL/kg bw

DOSE ADMINISTRATION:
- In the first and second step of the study, the test item was administered by gavage under a volume of 2.20 mL/kg bw (corresponding to 2000 mg/kg bw according to the density of 0.908) using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females/dose

Control animals:

other: Study no.: TAO-2014-001 (no treatment related changes were observed)

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed for any behavioural or toxic effects at 30 minutes, 1, 3, 4, 24 and 48 h after administration of the item and continued during 14 days following the administration of test item. Clinical observations and mortality were recorded every day for 14 days.
Bodyweight: Animals were weighed on Days 0 (just before administering the test item), 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anesthetized with sodium pentobarbital and administration continued to fatal levels and macroscopic examination was performed.

Statistics:

None

Preliminary study:

Not Applicable

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was observed in one rat treated at 2000 mg/kg bw (1/6), 25 h and 35 minutes post-dose, during the second step of the study.

Clinical signs:

other: - Mortality was preceded by an absence or decrease in spontaneous activity, Preyer's reflex, body temperature, muscle tone and righting reflex, myosis, lacrymation, bradypnea and staggering gait were noted on Day 0. - In the surviving animals treated at 2

Gross pathology:

Macroscopic examination of dead animal revealed a thinning and a red coloration of the fore stomach.
No macroscopic abnormalities were observed in surviving animals.

Other findings:

None

None

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

not classified according to the CLP Regulation (EC) N° 1272/2008

Conclusions:

The oral LD50 for dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in female rats. Therefore it is not classified according to the CLP Regulation (EC) N° 1272/2008.

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, groups (6 female rats/dose) of Sprague Dawley rats were given a single oral (gavage) dose of dihydroterpineol multiconstituent at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

One animal was died at 2000 mg/kg bw. Mortality was preceded by an absence or decrease in spontaneous activity, Preyer's reflex, body temperature, muscle tone and righting reflex, myosis, lacrymation, bradypnea and staggering gait were noted on Day 0. Similar clinical signs were observed in the surviving animals from 30 minutes postdose and were totally reversible at 24 h post-dose. Body weight gain of the treated animals was not affected by test item. Macroscopic examination of dead animal revealed a thinning and a red coloration of the fore stomach. No macroscopic abnormalities were observed in surviving animals. In this study, the oral LD50 of test item was considered to be higher than 2000 mg/kg bw in female rats.

 

Therefore, the oral LD50 for the test item is higher than 2000 mg/kg bw in female rats therefore it is not classified according to CLP Regulation (EC) N° 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

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:

04-18 February 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

13 September 2013

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: Elevage Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Males: 8 weeks; Females: 9 weeks
- Weight at study initiation: Males: 288-336 g; Females: 198-248 g
- Housing: Animals were housed in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid; During the treatment, the animals were kept in individual cages and after the removal of the patch on Day 1, the animals were put into their cage by group of 5.
- Diet: Foodstuff (SAFE, A04), ad libitum
- Water: Drinking water (tap water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: Approximately 13 changes/h
- Photoperiod: 12 h dark / 12 h light

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 h before the treatment, fur was removed from the dorsal area of the trunk of the test animals by clipping.

TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: Approximately 10 % of the body surface area
- Type of wrap if used: Test material was applied by topical application, under porous gauze dressing.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Dose volume: 2.20 mL/kg bw (corresponding to 2000 mg/kg bw according to the density of 0.908)
- Constant volume or concentration used: Yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: Study no.: TAD-2014-001 (no treatment related changes were observed)

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed for any behavioural or toxic effects on the major physiological functions at 1, 3 and 5 h post dose and thereafter every day for 14 days. Clinical observations and mortality were recorded every day for 14 days.
- The integrity of the skin on the application site was noted.
Bodyweight was recorded on Days 0 (just before administering test item), 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels and macroscopic examination was performed.

Statistics:

None

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Neither cutaneous reactions nor systemic clinical signs related to the administration of the test item were observed.

Gross pathology:

No macroscopic abnormalities were observed at necropsy.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in rats. Therefore it is not classified according to GHS and CLP Regulation (EC) N° 1272/2008.

Executive summary:

In an acute dermal toxicity study (limit test) performed according to OECD Guideline 402 and in compliance with GLP, a group of Sprague Dawley rats (5/sex/dose) were given a single dermal application of dihydroterpineol multiconstituent at 2000 mg/kg bw. The test item was applied on dorsal area of the trunk representing approximately 10 % of the total body surface area of the animals. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality was observed. Neither cutaneous reactions nor systemic clinical signs related to the administration of the test item were observed. Body weight gain of the treated animals was not affected by the test item. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 of the test item was considered to be higher than 2000 mg/kg bw in rats.

The acute dermal LD50 of dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) N° 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, groups (6 female rats/dose) of Sprague Dawley rats were given a single oral (gavage) dose of dihydroterpineol multiconstituent at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

One animal was died at 2000 mg/kg bw. Mortality was preceded by an absence or decrease in spontaneous activity, Preyer's reflex, body temperature, muscle tone and righting reflex, myosis, lacrymation, bradypnea and staggering gait were noted on Day 0. Similar clinical signs were observed in the surviving animals from 30 minutes postdose and were totally reversible at 24 h post-dose. Body weight gain of the treated animals was not affected by test item. Macroscopic examination of dead animal revealed a thinning and a red coloration of the fore stomach. No macroscopic abnormalities were observed in surviving animals. In this study, the oral LD50 of test item was considered to be higher than 2000 mg/kg bw in female rats.

Therefore, the oral LD50 for the test item is higher than 2000 mg/kg bw in female rats therefore it is not classified according to CLP Regulation (EC) N° 1272/2008.

In an acute dermal toxicity study (limit test) performed according to OECD Guideline 402 and in compliance with GLP, a group of Sprague Dawley rats (5/sex/dose) were given a single dermal application of dihydroterpineol multiconstituent at 2000 mg/kg bw. The test item was applied on dorsal area of the trunk representing approximately 10 % of the total body surface area of the animals. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality was observed. Neither cutaneous reactions nor systemic clinical signs related to the administration of the test item were observed. Body weight gain of the treated animals was not affected by the test item. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 of the test item was considered to be higher than 2000 mg/kg bw in rats.

The acute dermal LD50 of dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) N°1272/2008.

Justification for classification or non-classification

The oral LD50 for dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in female rats.

The acute dermal LD50 of dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in rats.

Therefore it is not classified according to GHS and CLP Regulation (EC) N° 1272/2008.