Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

- Acute toxicity: oral: 300 mg/kg bw < LD50 < 2000 mg/kg bw (OECD 420, GLP, K, rel. 1).

- Acute toxicity: inhalation: waiver.

- Acute toxicity: dermal: LD50 = 4680 mg/kg bw, read-across (similar to OECD 402, K; rel.2)

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 2012-09-11 to 2012-10-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 420 and in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP Compliance Monitoring Programme (inspected on 2012-07-10)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS (RccHanTM:WIST)
- Source: Harlan Laboratories UK Ltd, Oxon UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 151-180 g
- Fasting period before study: overnight. Food will be returned approximately 3 to 4 hours after dosing.
- Housing: in group of up to four in suspended solid-floor polypropylene cages furnished with wooflakes.
- Diet (e.g. ad libitum): Rodent 2014C Teklad Global Certified Diet ad libitum. Not contaminated.
- Water (e.g. ad libitum): Tap water ad libitum. Not contaminated.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
For the purpose of the 2000 mg/kg bw dose level, the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg bw dose level, the test item was freshly prepared, as required, as a solution in arachis oil BP
- Concentration in vehicle: 30 mg/mL
- Justification for choice of vehicle: the test item did not dissolve / suspend in distilled water.

DOSE VOLUME APPLIED:
- 300 mg/kg bw: 10 mL/ kg bw
- 2000 mg/kg bw: 0.932 mL/kg bw

- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg bw was chosen as the starting dose.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of mortality / morbidity inspection: twice daily, early and late, during normal working dates, once daily at weekends and public holidays. Due to a technical error, the Day 8 clinical observation for the initial animal treated at a dose level of 2000 mg/kg bw was not performed. This deviation was considered not to affect the purpose or integrity of the study as no signs of systemic toxicity were noted immediately before or after Day 8.
- Frequency of clinical observations: 30 min, 1, 2 and 4 hours after dosing, then at least once daily.
- Weighing: recorded on Day 0 (prior to dosing), Day 7 and 14, or at death.
- Necropsy of survivors performed: yes, gross necropsy on all animals. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
None
Preliminary study:
In the absence of data regarding the toxicity of the test item, 300 mg/kg bw was chosen as the starting dose. In the absence of mortality or evident toxicity at a dose level of 300 mg/kg bw, an additional animal was treated at 2000 mg/kg bw. In the absence of mortality at a dose level of 2000 mg/kg bw, an additional group of animals was treated at 2000 mg/kg bw. A total of five animals were therefore treated at a dose level of 2000 mg/kg bw in the study Due to mortality at a dose level of 2000 mg/kg bw, an additional group of animals was treated at 300 mg/kg bw. A total of five animals were therefore treated at a dose level of 300 mg/kg bw in the study.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Two animals were found dead one or two days after dosing with 2000 mg/kg bw.
Clinical signs:
other: - 2000 mg/kg bw: Signs of systemic toxicity noted in animals were hunched posture, ataxia, lethargy and occasional body tremors. Surviving animals appeared normal two hours, one or two days after dosing. - 300 mg/kg bw: No signs of systemic toxicity were
Gross pathology:
Abnormalities noted at necropsy of the animals that died during the study were abnormally red lungs, dark liver, dark or pale kidneys and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Other findings:
None

None

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
300 mg/kg bw < Oral LD50 Females < 2000 mg kg bw.
Under the test conditions, the test item is classified as Acute oral tox. 4 (H302: Harmful if swallowed) according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute oral toxicity study performed according to the OECD test guideline No. 420 and in compliance with GLP, groups of fasted, eight to twelve weeks of age Wistar (RccHanTM:WIST) female rats were given a single oral dose of test item undiluted or as a suspension in Arachis oil BP. Following a sighting test at dose levels of 300 mg/kg bw and 2000 mg/kg bw, a further group of four fasted females was given a single oral dose of test item at a dose level of 2000 mg/kg bw. Due to mortalities at a dose level of 2000 mg/kg bw, an additional group of four fasted females was given a single oral dose of test item, as a solution in arachis oil BP, at a dose level of 300 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Oral LD50 Females: in the range 300 - 2000 mg/kg bw.

Two animals treated at a dose level of 2000 mg/kg bw were found dead one or two days after dosing. There were no deaths at a dose level of 300 mg/kg bw. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg bw were hunched posture, ataxia, lethargy and occasional body tremors. There were no signs of systemic toxicity at a dose level of 300 mg/kg bw. Surviving animals showed expected gains in bodyweight. Abnormalities noted at necropsy of the animals that died during the study were abnormally red lungs, dark liver, dark or pale kidneys and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Under the test conditions, the test item is classified as Acute oral tox. 4 (H302: Harmful if swallowed) according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
The key study is GLP-compliant and of high quality (Klimisch score = 1).

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 (< 7.9 Pa at 20°C) and a low freezing point (<-20°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 = 4.8 at 25°C - from analogue, WS = 39.6 mg/L at 20°C).
Clinical signs:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 680 mg/kg bw
Quality of whole database:
The key study is of high quality (Klimisch score = 2).

Additional information

Acute toxicity: oral

A key study was identified (Harlan, 2013, rel.1). In this acute oral toxicity study performed according to the OECD test guideline No. 420 and in compliance with GLP, rats were given a single oral dose of cis-4-tert-butylcyclohexyl acetate undiluted or as a suspension in Arachis oil BP. Following a sighting test at dose levels of 300 mg/kg bw and 2000 mg/kg bw, a further group of four fasted females was given a single oral dose of test item at a dose level of 2000 mg/kg bw. Due to mortalities at a dose level of 2000 mg/kg bw, an additional group of four fasted females was given a single oral dose of test item, as a solution in arachis oil BP, at a dose level of 300 mg/kg bw.

Oral LD50 Females is in the range 300 - 2000 mg/kg bw.

Two animals treated at a dose level of 2000 mg/kg bw were found dead one or two days after dosing. There were no deaths at a dose level of 300 mg/kg bw. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg bw were hunched posture, ataxia, lethargy and occasional body tremors. There were no signs of systemic toxicity at a dose level of 300 mg/kg bw. Surviving animals showed expected gains in bodyweight. Abnormalities noted at necropsy of the animals that died during the study were abnormally red lungs, dark liver, dark or pale kidneys and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Similar findings were observed on the analogue substance, 4-tert-butylcyclohexyl acetate (Slepetys, 1979). Indeed, rats exposed to undiluted test material at dose levels ranging from 1870 to 4680 mg/kg bw also became hypoactive after dosing. In the first 24 hours, the principle clinical signs were tremors; twitching of the limbs and, at a low incidence, convulsions. Between 24 and 48 hours the principle signs were a reluctance to move. Thereafter, survivors showed few clinical signs except chromodacryorrhea. 1, 3, 5, 8 and 15 deaths out of 16 animals (8/sex) occurred at 1872, 2340, 2995, 3744, 4680 mg/kg bw, respectively. Deaths occurred after 12 hours and were spaced over the next six days. The most prominent sign at necropsy was congestion and early autolysis of the small intestine. The LD50 in this study was calculated to be 3323 mg/kg bw (Females).

Acute toxicity: dermal

No study was available on cis-4-tert-butylcyclohexyl acetate. Therefore an analogue approach using the supporting substance 4-tert-butylcyclohexyl acetate was followed to conclude on the acute dermal toxicity potential of cis-4-tert-butylcyclohexyl acetate (cf. Section 13 for read-across justification). In the limit acute dermal toxicity study performed before but similarly to the OECD guideline No. 402, groups of rabbits (3/sex) were occlusively exposed to undiluted 4 -tert-butylcyclohexyl acetate for 24 hours at dose of ca. 4680mg/kg bw (Slepetys, 1979). No mortality occurred during the study and no clinical signs were observed. There was no adverse effect on bodyweight gain. Slight to moderate erythema was observed during the first 24 hours after application. All rabbits exhibited a slight scaliness over the treated area, which was first observed on Day 8 and persisted to the end of the study.

Dermal LD50 Combined > 4680 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 (< 7.9 Pa at 20°C) and a low freezing point (<-20°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 = 4.8 at 25°C - from analogue, WS = 39.6 mg/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 via Oral route:

Based on the available information, the substance is classified under category 4 according to the CLP and the GHS as the LD50 is between 300 and 2000 mg/kg bw .

Acute toxicity via Dermal route:

Based on the available information, the test item is:

- not classified according to the CLP as the LD50 (analogue) is greater than 5000 mg/kg bw

- not classified according to the GHS as the LD50 (analogue) is greater than 5000 mg/kg bw.

Acute toxicity via 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 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 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 (Inhalation):

No information was available.

Aspiration hazard:

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