Reaction Mass of Cyclohexanepropanol, 2,2,6-trimethyla-propyl-, (alpha.R,1R,6S)- and Cyclohexanepropanol,2,2,6-trimethyl-a-propyl-, [1a(S*),6b]- (9CI)

Endpoint summary

Description of key information

Acute toxicity: oral: LD50 > 5000 mg/kg bw (similar to OECD 401, K, rel. 2).

Acute toxicity: dermal: LD50 > 2000 mg/kg bw (similar to OECD 402, K, rel. 2).

Acute inhalation: waiver

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 June 14 to June 28, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study comparable to OECD test guideline No. 401 but GLP status not reported.

Qualifier:

equivalent or similar to guideline

Guideline:

other: Section 1500.3 - Federal Hazardous Substances Act Regulations - 16 CFR

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

not specified

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: Ace Animals, Inc., Boyertown, PA.
- Age at study initiation: no data
- Weight at study initiation: 200-300 g
- Fasting period before study: overnight deprivation of food
- Housing: 5 rats/cage by sex, in stainless steel cages with elevated wire mesh flooring
- Diet (e.g. ad libitum): Wayne Lab-Blox ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: appropriate time

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23
- Humidity (%): 45-55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

None

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: frequently on the day of dosage, and twice per day thereafter.
- Frequency of weighing: on the day of dosage (individually), and on Day 7 and 14 after dosing (grouped)
- Necropsy of survivors performed: yes, gross examinations

Statistics:

none

Preliminary study:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: All animals appeared normal throughout the 14 day observation period

Gross pathology:

No gross abnormalities

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Oral LD50Combined > 5000 mg/kg bw.
Under the test conditions, the test material is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In a limit acute oral toxicity study performed similarly to the OECD test guideline No. 401, a group of fasted, Sprague-Dawley rats (5/sex) was administered a single oral dose of undiluted test material at 5000 mg/kg bw by gavage. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. No gross abnormalities were observed at necropsy.

 

Oral LD50Combined > 5000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The key study is of good quality (Klimisch score = 2) although GLP status is not reported.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with Column 2 of REACH Annex VIII, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. In the present case, inhalation exposure will be lower than dermal exposure because the registered substance has a low vapour pressure (0.194 Pa at 25°C) and a low freezing point (<-7°C), so the potential for the generation of inhalable forms is low. Dermal exposure is the more likely route of exposure based on physico-chemical properties (Log Kow = 5.79 at 25°C, WS = 125-285 µg/L at 20°C).

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 June 15 to June 29, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study comparable to OECD test guideline No. 402 with deviations not affecting the integrity of the result. Indeed, only 6 animals were tested instead of the 10 required by the OECD Test Guideline No. 402 for a limit test. However having 4 more animals would not impact the LD50 value since no mortality occurred within this study. Moreover half of the animals had abraded skin which improved skin permeability, and therefore absorption. GLP status not reported.

Qualifier:

equivalent or similar to guideline

Guideline:

other: Section 1500.4 - Federal Hazardous Substance Act Regulation - 16 CFR

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

Limit test using 6 animals instead of 10, half of them having abraded skin

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA.
- Age at study initiation: no data
- Weight at study initiation: 2.3-3.0 kg bw.
- Fasting period before study: no.
- Housing: individually, in stainless steel cages with elevated wire mesh flooring.
- Diet (e.g. ad libitum): Wayne 15% Rabbit ration ad libitum.
- Water (e.g. ad libitum): tap water ad libitum.
- Acclimation period: appropriate time.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.5 - 23
- Humidity (%): 40-45
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: backs (clipped skin, 3 with abraded skin).
- % coverage: approximately 10%.
- Type of wrap if used: large gauze patches, impervious material wrapped snugly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no (wiping only)
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/kg bw.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations (systemic and topical): frequently during the first day, and twice per day thereafter (morning and afternoon).
- Frequency of weighting: on the day of dosage, weekly thereafter, and prior to sacrifice.
- Necropsy of survivors performed: yes (gross necropsy)

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.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: None.

Gross pathology:

No gross abnormalities were noted.

Other findings:

Mild erythema and severe oedema were observed after unwrapping at 24 hours. Eschar was noted for all animals by day 4 which was still evident at 14 days.

None

Interpretation of results:

GHS criteria not met

Conclusions:

Dermal LD50Combined > 2000 mg/kg bw.
Under the test conditions, the test material is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In a limit acute dermal toxicity study performed similarly to the OECD test guideline No. 402, New Zealand White rabbits (3/sex) were occlusively exposed to undiluted test material for 24 hours at dose of 2000 mg/kg bw. The animals were observed for mortality, clinical signs including dermal reactions and body weight for 14 days and then necropsied for macroscopic observations.

No mortality and no clinical signs were observed during the study. A loss of body weight was noted for 1/3 female at 7 days.

Mild erythema and severe oedema were observed after unwrapping at 24 hours. Eschar was noted for all animals by day 4 which was still evident at 14 days.

Dermal LD50Combined > 2000 mg/kg bw.

Under the test conditions, the test material is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is of good quality (Klimisch score = 2) although GLP status is not reported.

Additional information

Acute toxicity via oral route:

A key study was identified (Biosearch Inc., 1984). In this limit acute oral toxicity study performed similarly to the OECD test guideline No. 401, rats (5/sex) were administered a single oral dose of undiluted test material at 5000 mg/kg bw by gavage. No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. No gross abnormalities were observed at necropsy.

Oral LD50Combined > 5000 mg/kg bw.

Acute toxicity via dermal route:

A key study was identified (Biosearch Inc., 1984). In this limit acute dermal toxicity study performed similarly to the OECD test guideline No. 402, rabbits (3/sex, half clipped and half abraded)were occlusively exposed to undiluted test material for 24 hours at dose of 2000 mg/kg bw. No mortality and no clinical signs were observed during the study. A loss of body weight was noted for 1/3 female at 7 days. Mild erythema and severe oedema were observed after unwrapping at 24 hours. Eschar was noted for all animals by day 4 which was still evident at 14 days.

Dermal LD50Combined > 2000 mg/kg bw.

Acute toxicity: inhalation

In accordance with Column 2 of REACH Annex VIII, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. In the present case, inhalation exposure will be lower than dermal exposure because the registered substance has a low vapour pressure (0.194 Pa at 25°C) and a low freezing point (<-7°C), so the potential for the generation of inhalable forms is low. Dermal exposure is the more likely route of exposure based on physico-chemical properties (Log Kow = 5.79 at 25°C, WS = 125-285 µg/L at 20°C).

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).

Self classification:

Acute toxicity (Oral):

The substance is not classified according to the CLP and the GHS as the LD₅₀ is higher than 5000 mg/kg bw

Acute toxicity (Dermal):

The substance is:

- not classified according to the CLP as the dermal LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS as the dermal LD50 is higher than 2000 mg/kg bw and the substance does not meet the specific criteria for the Category 5 defined in the GHS.

Acute toxicity (Inhalation):

No information was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, dermal for a Category 1 classification (C ≤ 1000 mg/kg bw) and at the guidance value, dermal for a Category 2 classification (2000 mg/kg bw ≥ C > 1000 mg/kg bw). No classification required.

Specific target organ toxicity: single exposure (Inhalation):

No information was available.

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral study, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.