Registration Dossier

Administrative data

Description of key information

Oral (similar to OECD 401), rat: LD50 = 4200 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
limited documentation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
no
Remarks:
study performed prior to implementation of GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
2000, 2500, 3200, 4000 and 5000 mg/kg bw
No. of animals per sex per dose:
10 animals per dose (no data on sex)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Sex:
not specified
Dose descriptor:
LD50
Effect level:
4 200 mg/kg bw
Based on:
test mat.
95% CL:
> 3.62 - < 4.87
Mortality:
- 2000 mg/kg bw: 0/10
- 2500 mg/kg bw: 1/10 (The animal died on day 3 of the observation period.)
- 3200 mg/kg bw: 2/10 (The animals died on day 1 and 3 of the observation period, respectively.)
- 4000 mg/kg bw: 4/10 (3 animals died on day 1 and one animal on day 2 of the observation period.)
- 5000 mg/kg bw: 8/10 (7 animals died on day 1 and one animal on day 2 of the observation period.)
Clinical signs:
Immediate stimulation followed by ataxia were observed.
Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
A single dose oral toxicity test of 4-tert-butylcyclohexanol in rats revealed an LD50 value of 4200 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises a study which alone is regarded insufficient for assessment (Klimisch score 4). However, this study and extrapolation from the oral route provide sufficient weight of evidence for hazard assessment leading to an endpoint conclusion.

Additional information

Oral

The acute toxicity via the oral route of 4-tert-butylcyclohexanol has been investigated in two studies.

In a standard acute toxicity study performed similar to OECD Guideline 401, 10 rats per dose were orally administered 4-tert-butylcylohexanol at dose levels of 2000, 2500, 3200, 4000 and 5000 mg/kg bw (Denine_1973). Animals were subsequently observed for a period of 14 days. No mortality was observed in the lowest dose group of 2000 mg/kg bw. 1, 2, 4 and 8 rats per group died in the 2500, 3200, 4000 and 5000 mg/kg bw dose groups, respectively. All deaths occurred within 3 days after administration. Immediate stimulation followed by ataxia was observed, but it is not stated in how many animals and in which group. Based on the results, the LD50 value was determined to be 4200 mg/kg bw.

In a further study similar to OECD Guideline 401 an LD50 value of 4000 mg/kg bw was obtained for rats (BASF, 1975). Dyspnea, apathy, tremor and partially aggressiveness were noted, as well as an initially body weight loss. Acute cardiac dilatation, congestive hyperemia and sporadic yellow-/clay-coloured livers were observed at pathology. Based on limited documentation this study was considered insufficient for assessment.

 

Inhalation

An inhalation risk test was conducted with 4-tert-butylcyclohexanol in rats (BASF, 1975). No mortality was reported after an 8 hour exposure to an air saturated with vapour at 20 °C, which corresponds to a value of 0.221 mg/L based on QSAR calculation (Danish EPA Database, 2004). No clinical signs were noted and there were no findings at necropsy.

4-tert-butylcyclohexanol is a viscid substance with a low vapour pressure (6 Pa at 25 °C). Thus exposure via the inhalation route can be considered negligible and formation of aerosols is unlikely. No spraying tasks are included in the identified uses.

Due to the low vapour pressure, exposure considerations und animal welfare considerations, further testing by the inhalation route does not need to be conducted in accordance with Annex VIII, Column 2, Section 8.5.2, of Regulation (EC) No 1907/2006.

 

Dermal

There are no reliable data on acute dermal toxicity. Only the result of one dermal study is available, in which 6 rabbits were dermally exposed to the test substance for an undefined time period (Denine_1973). No mortality occurred and the LD50 was reported to be higher than 5000 mg/kg bw. No clinical signs of toxicity were observed up to the end of the observation period. However, details neither on study design (e.g. duration and type of coverage) nor on test animals are available. Due to the limited information, the data are not considered sufficient for assessment. Further information on dermal toxicity can be obtained from a reliable skin irritation study performed with 6 rabbits (82-0310-DKT). Besides the slight local reactions, no mortality occurred and no general signs of toxicity were reported after applying 550 mg test substance prepared with a few drops of paraffin to the rabbits’ skin (4 h exposure, semi-occlusive treatment).

A general prerequisite for systemic toxicity after dermal application is the permeability of the skin for the applied substance. Based on the physico-chemical parameters, a high dermal absorption potential was calculated and can be assigned to a dermal absorption of 80% (QSAR published by Potts and Guy, 1992; Kroes et al., 2007; Mostert and Goergens, 2011). Taking into account an oral LD50 of 4200 mg/kg bw for rats and an dermal absorption of 80%, extrapolation results in a dermal LD50 value > 5000 mg/kg bw that does not trigger a classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC. This is consistent with the data from the available acute dermal toxicity data. Route-to-route extrapolation can be considered adequate for the purpose of classification and labelling and for the risk assessment of acute dermal toxicity of 4-tert-butylcyclohexanol. Moreover, taking into account exposure and animal welfare considerations, further testing by the dermal route is not appropriate.


Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study based on overall quality assessment.

Justification for selection of acute toxicity – inhalation endpoint
The available information (inhalation risk test) comprises a study which alone is regarded insufficient for assessment (Klimisch score 4). However, there is no further study required since exposure of humans via inhalation is unlikely taking into account the physico-chemical properties of the substance and exposure considerations.

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is based on a weight of evidence taking into account an available study and route-to-route extrapolation.

Justification for classification or non-classification

Oral

The available data on acute oral toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

Inhalation

There is no valid data available on acute inhalation toxicity.

Dermal

Based on extrapolation from the oral route and supported by an acute dermal toxicity study by Denine (1973) reporting an LD50 > 5000 mg/kg bw, the test substance do not met the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.