4,4'-cyclohexylidenedi-o-cresol

Endpoint summary

Description of key information

ORAL

LD50 > 2000 mg/kg bw in the rat (male/female); OECD 423 and EPA OPPTS 870.1100

DERMAL

LD50 > 2000 mg/kg bw in the rabbit (male/female); OECD 402 and EPA 870.1200

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:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Six outbred albino rats per sex were received from the supplier. Female rats were nulliparous and non-pregnant. They weighed 216.5-247.8 g and were at least 8 weeks old at the start of the study. They were single housed upon arrival in polycarbonate cages with hardwood chip bedding. The animals were acclimated for at least 5 days prior to dosing. Tap water was provided ad libitum throughout the study and feed was provided ad libitum, with the exception of overnight prior to dosing. The temperature and humidity were maintained at 68 ± 5 °F and 30 - 70 %, respectively. Room lights were on a 12-hour light/dark cycle.

Route of administration:

oral: gavage

Vehicle:

other: methanol

Details on oral exposure:

DMBPC was dissolved in methanol prior to dosing. The dosing volume did not exceed 1 mL/100 g body weight.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

Food was withheld from the animals the night prior to dosing. Animals were administered a single dose of DMBPC by oral gavage. After dosing, the animals were returned to their cages and supplied with feed and water ad libitum.

Careful clinical observations were made at least twice on the day of dosing. Animals were observed daily for 14 days for clinical manifestations. Animals were weighed on Day 0 (prior to dose administration), Day 7 and Day 14.

On Day 14 animals were sacrificed by CO2 inhalation and a gross necropsy was performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the duration of the study.

Clinical signs:

other: No clinical signs of toxicity were observed in any animals over the course of the study.

Gross pathology:

No unusual findings were found during necropsy for the animals euthanised at study termination.

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study, DMBPC was determined to have an acute oral LD50 of greater than 2000 mg/kg.

Executive summary:

The acute toxicity potential of the test material was investigated in a study conducted in accordance with the standardised guidelines OECD 423 and EPA OPPTS 870.1100 under GLP conditions using the acute toxic class method.

Six Sprague-Dawley rats were exposed to the test material at a limit dose of 2000 mg/kg bw in methanol by oral gavage.

Careful clinical observations were made at least twice on the day of dosing. Animals were observed daily for 14 days for clinical manifestations. Animals were weighed on Day 0 (prior to dose administration), Day 7 and Day 14. On Day 14, animals were sacrificed by CO₂ inhalation and a gross necropsy was performed.

All animals survived the duration of the study. No clinical signs of toxicity were observed in any animals over the course of the study and all animals gained weight over the course of the study. No unusual findings were found during necropsy for the animals euthanised at study termination.

Under the conditions of this study, DMBPC was determined to have an acute oral LD50 of greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The study was conducted in accordance with standardised guidelines under GLP conditions and the study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997). The quality of the database if therefore considered to be high.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with section 8.5 of Column 2 of REACH Annex VIII, it is considered justified to omit this study on the grounds that testing is scientifically unjustified. Having assessed the likely routes of exposure, it is considered that testing via the inhalation route is not appropriate given that the particle size of the material is such that it is essentially non-respirable and the vapour pressure was calculated to be sufficiently low as to suggest that exposure to the substance via the inhalation route is not anticipated to occur during its envisaged life-cycle. Instead, acute toxicity data are provided for the oral and dermal routes.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female (nulliparous and non-pregnant) New Zealand White rabbits were received from the supplier. The animals weighed 2.06 - 2.60 kg and were at least 12 weeks old and were individually housed upon arrival in stainless steel suspended cages with hardwood chip bedding. The animals were acclimated for at least 5 days prior to dosing. Water and feed were provided ad libitum. The temperature and humidity were maintained at 68 ± 5 °F and 30 - 70 %, respectively. Room lights were on a 12-hour light/dark cycle.

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

The application site, not less than 10 % of the body surface, was prepared approximately 24 hours prior to dosing by clipping the skin of the trunk free of hair. DMBPC, as received from the Sponsor, was slightly moistened to form a paste and introduced under gauze patches (two single layers thick) and applied directly to the clipped skin of 10 animals. The animals were immobilised and the patches were secured in place by wrapping the entire trunk of the animal with an impervious bandage. Test sites were secured to prevent the animals from ingesting the test substance. After the completion of the 24-hour exposure period, the wrapping was removed and the skin was gently wiped to remove any test substance still remaining.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

Five animals/sex were dosed at 2000 mg/kg (limit test). The animals were observed frequently during the first day and then a careful clinical examination was made at least once a day through 14 days. The test site of each animal was also observed for signs of erythema and oedema after the exposure period according to the Draize Scale for Scoring Skin Reactions. Animals were weighed at Day 0 (prior to dose administration), Day 7 and Day 14. Changes in body weights were calculated and recorded. At the end of the study, all animals were sacrificed by an injectable barbiturate and a gross necropsy was performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the duration of the study.

Clinical signs:

other: No clinical signs of toxicity were observed in any animals over the course of the study. All animals displayed normal skin reactions over the course of the study.

Gross pathology:

No unusual findings were found during necropsy for the animals euthanized at study termination.

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study, DMBPC was determined to have an acute dermal LD50 of greater than 2000 mg/kg.

Executive summary:

The potential of the test material to cause acute toxicity was investigated in accordance with the standardised guidelines OECD 402 and EPA OPPTS 870.1200 under GLP conditions using the standard acute method.

Five male and 5 female clipped New Zealand White rabbits were exposed to a 2000 mg/kg bw limit dose of the test material in an occlusive fashion for 24 hours. After the completion of the 24-hour exposure period, the wrapping was removed and the skin was gently wiped to remove any test substance still remaining.

The animals were observed frequently during the first day and then a careful clinical examination was made at least once a day through 14 days. The test site of each animal was also observed for signs of erythema and oedema after the exposure period according to the Draize Scale for Scoring Skin Reactions. Animals were weighed at Day 0 (prior to dose administration), Day 7 and Day 14. Changes in body weights were calculated and recorded. At the end of the study, all animals were sacrificed by an injectable barbiturate and a gross necropsy was performed.

All animals survived the duration of the study. No clinical signs of toxicity were observed in any animals. All animals displayed normal skin reactions and all animals gained weight over the course of the study. No unusual findings were found during necropsy for the animals that were euthanised at study termination.

Under the conditions of this study, DMBPC was determined to have an acute dermal LD50 of greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The study was conducted in accordance with standardised guidelines under GLP conditions and the study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997). The quality of the database if therefore considered to be high.

Additional information

Oral

The acute toxicity potential of the test material was investigated in a study conducted in accordance with the standardised guidelines OECD 423 and EPA OPPTS 870.1100 under GLP conditions using the acute toxic class method.

Six Sprague-Dawley rats were exposed to the test material at a limit dose of 2000 mg/kg bw in methanol by oral gavage.

Careful clinical observations were made at least twice on the day of dosing. Animals were observed daily for 14 days for clinical manifestations. Animals were weighed on Day 0 (prior to dose administration), Day 7 and Day 14. On Day 14, animals were sacrificed by CO₂ inhalation and a gross necropsy was performed.

All animals survived the duration of the study. No clinical signs of toxicity were observed in any animals over the course of the study and all animals gained weight over the course of the study. No unusual findings were found during necropsy for the animals euthanised at study termination.

Under the conditions of this study, DMBPC was determined to have an acute oral LD50 of greater than 2000 mg/kg.

 

Inhalation

In accordance with section 8.5 of Column 2 of REACH Annex VIII, it is considered justified to omit this study on the grounds that testing is scientifically unjustified.

Having assessed the likely routes of exposure, it is considered that testing via the inhalation route is not appropriate given that the particle size of the material is such that it is essentially non-respirable and the vapour pressure was calculated to be sufficiently low as to suggest that exposure to the substance via the inhalation route is not anticipated to occur during its envisaged life-cycle. Instead, acute toxicity data are provided for the oral and dermal routes.

 

Dermal

The potential of the test material to cause acute toxicity was investigated in accordance with the standardised guidelines OECD 402 and EPA OPPTS 870.1200 under GLP conditions using the standard acute method.

Five male and 5 female clipped New Zealand White rabbits were exposed to a 2000 mg/kg bw limit dose of the test material in an occlusive fashion for 24 hours. After the completion of the 24-hour exposure period, the wrapping was removed and the skin was gently wiped to remove any test substance still remaining.

The animals were observed frequently during the first day and then a careful clinical examination was made at least once a day through 14 days. The test site of each animal was also observed for signs of erythema and oedema after the exposure period according to the Draize Scale for Scoring Skin Reactions. Animals were weighed at Day 0 (prior to dose administration), Day 7 and Day 14. Changes in body weights were calculated and recorded. At the end of the study, all animals were sacrificed by an injectable barbiturate and a gross necropsy was performed.

All animals survived the duration of the study. No clinical signs of toxicity were observed in any animals. All animals displayed normal skin reactions and all animals gained weight over the course of the study. No unusual findings were found during necropsy for the animals that were euthanised at study termination.

Under the conditions of this study, DMBPC was determined to have an acute dermal LD50 of greater than 2000 mg/kg.

 

 

Justification for selection of acute toxicity – oral endpoint

Only one study available.

 

Justification for selection of acute toxicity – dermal endpoint

Only one study available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to either acute oral toxicity or acute dermal toxicity.