4-trans-Butyl-4'-trans-propyl-[1,1'-bicyclohexyl]

Endpoint summary

Description of key information

The acute toxicity of the test item was investigated in an acute toxicity study on rats. The test animals showed no clinical signs (and no mortality) up to the limit dose after oral administration. Hence, the LD50 is above 2000 mg/Kg bw.

The subsequent evaluation on the necessity of a acute test via a second route was done in accordance with Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance, Version 6.0, July 2017, p 374f.

A DermWin calculation shows a dermally absorbed dose of 3.2*10 -6 to 3.3 -10 -5 mg/cm2/event. Based on the very low dermally absorbed rate and the absence of systemic effects after acute oral administration, a study on acute dermal toxicity is not required.

Furthermore, based on the lack of systemic toxicity after acute oral adminsitration, it is more than evident that an acute study on inhalation would not show any different outcome. Therefore, and due to animal welfare reasons a study on acute inhalation is not required.

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:

Oct 19 - Nov 02, 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was performed according to GLP and the methods applied are fully compliant with OECD TG 401.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: 6 to 9 weeks
- Weight at study initiation: 177 (161 - 198) g
- Fasting period before study: 17 hours before until up to 4 hours after treatment
- Housing: separately in type III Makrolon cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 23 °C
- Humidity (%): 22 to 34 %
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime

IN-LIFE DATES: From: day 1 To: day 15

Route of administration:

oral: gavage

Vehicle:

paraffin oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100 g/L
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: excellent vehicle performance in long range historical data


MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 (m) / 5 (f)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

Standard statistical methods have been applied for data processing.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All rats survived the observation period.

Clinical signs:

No signs of toxicity were seen after treatment with 2000 mg/kg.
Wet anal region and wet fur at the abdomen on study days 1 and 2 due to liquid paraffin was observed.

Body weight:

The body weight development of the rats was inconspicuous during the study.

Gross pathology:

The gross pathological examination revealed no organ alterations.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Executive summary:

Study design

In this study, the acute toxicity of the test material in rats after single oral administration of 2000 mg/kg body weight was investigated. The study was performed according to the OECD Guideline for Testing of Chemicals, No. 401.

Results

No signs of toxicity were seen in the rats (5 males, 5 females) after treatment with 2000 mg/kg of the test item. Wet anal region and wet fur at the abdomen was observed on study days 1 and 2 due to liquid paraffin.
The body weight development of the rats was inconspicuous during the study.
There were no deaths during the course of the study.
The gross pathological examination revealed no organ alterations.

Conclusion

Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD₅₀value is higher than 2000 mg/kg after single oral administration in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 401.

Justification for selection of acute toxicity – dermal endpoint
On 15 July 2014 the Competent Authorities for REACH and CLP (Caracal) have agreed that substances that are not toxic in acute oral tests need no longer be tested for acute dermal toxicity. Caracal agreed on proposals to amend REACH Annex VIII (point 8.5.3) so that substances that have not shown oral acute toxicity up to a limit dose of 2000mg/kg bodyweight would not also require dermal data. The test material does not provide evidence for acute oral toxicity. The LD50 exceeds 2000 mg/kg bw. Therefore no further testing for dermal toxicity is justified.

Justification for classification or non-classification

Based on the data provided, the test item is not classified for acute oral toxicity according to Regulation (EC) No 1272/2008.