Cyclohexylbenzene

Endpoint summary

Description of key information

Oral LD50: > 2000 mg/kg bw.
Dermal LD50: > 2000 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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented GLP study according to international guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

adopted 21 September 1998

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CD (Crl: CD® (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: ≥ 200g
- Fasting period before study: overnight immediately before dosing
- Housing: females individually and males in group of 3 in solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK) with exception of an overnight fast immediately before dosing and approximately 3 to 4 h after dosing
- Water: ad libitum
- Acclimation period: ≥ 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): ≥ 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Observations for deaths or overt signs of toxicity 1/2, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

other: Hunched posture was noted in 2 females. Signs of systemic toxicity also noted in one of these females were decreased respiratory rate, laboured respiration, ataxia and emaciation. These 2 females recovered 2 or 6 days after dosing. There were no signs of

Gross pathology:

No abnormalities

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) in the Sprague-Dawley CD (Crl CD® (SD) IGS BR) strain rat was found to be greater than 2000 mg/kg bw.

Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD (Crl CD® (SD) IGS BR) strain rat. The study was carried out according to OECD guideline 425.

One fasted female animal was treated with the test material at dose level of 2000 mg/kg. A second and a third fasted female rat were also treated at a dose level of 2000 mg/kg. This was then followed by a group of 3 fasted male rats at the same dose level.

The test material was administered orally undiluted. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths. Hunched posture was noted in 2 females. Signs of systemic toxicity also noted in one female were decreased respiratory rate, laboured respiration, ataxia and emaciation. There were no signs of systemic toxicity noted in one female and all males.

All animals showed expected gains in body weight over the study period. No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) was found to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Two K1 and two K4 studies available.

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:

2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to international guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2-3 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum (LABDIET 5322, PMI Nutrition International, Nottingham, UK)
- Water: ad libitum
- Acclimation period: ≥ 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): ≥ 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximating to 10% of the total body surface area
- Type of wrap if used: a piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the bandage was carefully removed and the treated skin decontaminated to remove any residual test material
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2.15 ml/kg

Duration of exposure:

24 h

Doses:

2000 mg/kg

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 and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. After removal of the dressings and subsequently once daily for 14 days, the test sites were examined and the presence or absence of any dermal irritation recorded accordingly.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No

Clinical signs:

other: No signs of systemic toxicity

Gross pathology:

No abnormalities

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the New Zealand White rabbit was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the New Zealand White rabbit. The study was carried out according to OECD guideline 402.

A group of ten animals (5 males and 5 females) was given a single 24 -h semi-occluded dermal application of undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

No deaths and no signs of systemic toxicity were observed. Signs of skin irritation noted were well-defined erythema, very slight to slight oedema, loss of skin elasticity and flexibility, light brown discolouration of the epidermis, superficial cracking of the epidermis, crust formation, a hardened light brown coloured scab, slight desquamation and fissuring. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the New Zealand White rabbit was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One K1 and one K4 study available.

Additional information

In total 3 key studies are available in which the acute toxicity of cyclohexylbenzene is assessed, 2 addressing oral toxicity, and 1 on dermal acute toxicity.

Oral toxicity

The key studies on oral toxicity (Sanders, 2001a; Sanders 2001b) both used the up-and-down procedure according to GLP and the OECD 425 guideline. In this procedure, one fasted female animal was treated with the test material at dose level of 2000 mg/kg. A second and a third fasted female rat were also treated at a dose level of 2000 mg/kg. This was then followed by a group of 3 fasted male rats at the same dose level. No deaths occurred in the two studies.

The acute oral LD50 of the test material in the Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rat was found to be greater than 2000 mg/kg bw.

Dermal toxicity

The key study on dermal toxicity (Sanders, 2001c) is carried out according to OECD guideline 402.

A group of ten animals (5 males and 5 females) was given a single 24 -h semi-occluded dermal application of undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. No deaths and no signs of systemic toxicity were observed. Signs of skin irritation noted were well-defined erythema, very slight to slight oedema, loss of skin elasticity and flexibility, light brown discolouration of the epidermis, superficial cracking of the epidermis, crust formation, a hardened light brown coloured scab, slight desquamation and fissuring. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the New Zealand White rabbit was found to be greater than 2000 mg/kg bodyweight.

The findings of the available supporting studies for acute oral and acute dermal toxicity are in line with those of the key studies.

Justification for selection of acute toxicity – oral endpoint
The study is GLP compliant and has Klimisch score 1.

Justification for selection of acute toxicity – dermal endpoint
The study is GLP compliant and has Klimisch score 1.

Justification for classification or non-classification

According to the criteria described in section 3.1.2 of Annex I to EU Regulation n° 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP), the LD50 values > 2000 mg/ kg bw as determined in the acute oral and acute dermal toxicity tests do not require a classification for acute toxicity.

According to the criteria described in section 3.2.1 - 3.2.3 of Annex VI to Council Directive 67/548/EEC on the Classification, Packaging and Labelling of Dangerous Substances (DSD), the results of the acute oral and acute dermal toxicity tests do not require a classification for acute toxicity.