3,3,5-trimethylcyclohexyl methacrylate

Endpoint summary

Description of key information

To evaluate the acute toxicity potential of 3,3,5 -trimethylcyclohexyl-methacrylate, two studies are available. An acute study by oral route showed no mortality at the dose of 5000 mg/kg/day in rats. An acute study by dermal route on an analogue showed no mortality at the dose of 2000 mg/kg/day in rats.

No data is available by inhalation.

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:

January-February 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland
- Age at study initiation: 8-10 weeks
- Weight at study initiation: males = 173-256g ; females = 150-164g
- Fasting period before study: yes (12/18 hours)
- Housing: by group of 3
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

The test article was placed into a glass beaker on a tared balance and the vehicle (PEG400) was added. A weight by weight susmension was prepared using a homogenizer. Homogeneity of the test article in the vehicle was maintained during treatment using the magentic stirrer.
The animals received the test article on a mg/.kg bw based by oral gavage after being fasted for 12 to 18 hours (access to water was not interrupted). Food was again presented approximately one hour after dosing.
Volumes of administration : 10 ml (1000 mg/kg), 20 ml (5000 mg/kg).

Doses:

1000 and 5000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:Viability was confirmed and recorded four times during test day 1 and daily days 2-15. each animal had an examination for changes in appearance and behavior four times during day 1, and daily during days 2-15.
- Frequency of weighing: on test days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes

Statistics:

no

Preliminary study:

no

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality was observed over a period of 15 days after the single administration.

Clinical signs:

other: sedation, dyspnea, curved body position and ruffled fur were observed in animals exposed to 1000 and 5000 mg/kg. The symptoms were more pronounced in the higher dose group. All animals recovered within 6 to 7 observation days.

Gross pathology:

At the necropsy, reddish testes were observed in one male rat of the 5000 mg/kg group. No other macroscopic organ changes were observed.

Other findings:

no

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion , the acute oral LD0 of 3,3,5 -trimethylcyclohexylmethacrylate was estimated to be higher than 5000 mg/kg in rat.

Executive summary:

The test article 3,3,5 -trimethylcyclohexylmethacrylate was administered to rats of both sexes by oral gavage, at doses from 1000 and 5000 mg/kg.

No mortality was observed over a period of 15 days after the single administration. However, sedation, dyspnea, curved body position and ruffled fur were observed in animals exposed to 1000 and 5000 mg/kg. The symptoms were more pronounced in the higher dose group. All animals recovered within 6 to 7 observation days. At the necropsy, reddish testes were observed in one male rat of the 5000 mg/kg group. No other macroscopic organ changes were observed.

In conclusion , the acute oral LD0 of 3,3,5 -trimethylcyclohexylmethacrylate was estimated to be higher than 5000 mg/kg in rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

The study is considered as valid with a klimisch score of 1.

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:

05 December 2016 - 23 December 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24th February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EC) No. 440/2008, Part B.3, 30 May 2008.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age/Weight: on the day of treatment, the animals were approximately 8 weeks old. The individual body weight of each individual was within ± 20% of the mean body weight of all the study animals of the same sex (224 g for females and 358 g for males).
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 01 December 2016 to 23 December 2016

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure
- Washing: at 24h post-exposure, with a moistened cotton pad

TEST MATERIAL
- Amount applied: 2000 mg/kg
- Constant volume: no

Duration of exposure:

24h

Doses:

2000 mg/kg

No. of animals per sex per dose:

five males and five females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on Day 1; then on Days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Statistics:

no

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: On Day 1, ptyalism was noted in 1/5 female and chromodacryorrhea was seen in 1/5 male. No other clinical signs were noted thereafter. Local reactions at the injection site were recorded and consisted in very slight to well-defined erythema in all animal

Gross pathology:

There were no macroscopic findings at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD0 of the test item was higher than 2000 mg/kg in rats.

Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item, following a single dermal application to rats. This study was based on the international guidelines (OECD No. 402 and Council Regulation No. 440/2008 of 30 May 2008, Part B.3) and was performed in compliance with the principles of Good Laboratory Practice.

The test item was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by an aerated hypoallergenic dressing for 24 hours. Each animal was observed at least once a day for mortality and clinical signs for 15 days. From Day 2, any local reactions at the treatment site were also noted. Body weight was recorded on Day 1 and then on Days 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved.

No unscheduled deaths occurred during the study. On Day 1, ptyalism was noted in 1/5 female and chromodacryorrhea was seen in 1/5 male. No other clinical signs were noted thereafter in any animals. Local reactions were recorded at the injection site and consisted in very slight to well-defined erythema, dryness and/or desquamation and scabs. 

Body weight of animals was unaffected by the test item treatment. There were no macroscopic findings at necropsy.

In conclusion, the dermal LD0 of the test item was higher than 2000 mg/kg in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study is considered as valid with a klimisch score of 1.

Additional information

Acute study by oral route (Ullmann, 1984a) :

The test article 3,3,5 -trimethylcyclohexylmethacrylate was administered to rats of both sexes by oral gavage, at doses from 1000 and 5000 mg/kg.

No mortality was observed over a period of 15 days after the single administration. However, sedation, dyspnea, curved body position and ruffled fur were observed in animals exposed to 1000 and 5000 mg/kg. The symptoms were more pronounced in the higher dose group. All animals recovered within 6 to 7 observation days. At the necropsy, reddish testes were observed in one male rat of the 5000 mg/kg group. No other macroscopic organ changes were observed.

In conclusion , the acute oral LD0 of 3,3,5 -trimethylcyclohexylmethacrylate was estimated to be higher than 5000 mg/kg in rat.

Acute dermal toxicity (Bouhraoua 2017) on analogue substance:

 The objective of this study was to evaluate the potential toxicity of the test item, following a single dermal application to rats. This study was based on the international guidelines (OECD No. 402 and Council Regulation No. 440/2008 of 30 May 2008, Part B.3) and was performed in compliance with the principles of Good Laboratory Practice.

The test item was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by an aerated hypoallergenic dressing for 24 hours. Each animal was observed at least once a day for mortality and clinical signs for 15 days. From Day 2, any local reactions at the treatment site were also noted. Body weight was recorded on Day 1 and then on Days 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved.

No unscheduled deaths occurred during the study. On Day 1, ptyalism was noted in 1/5 female and chromodacryorrhea was seen in 1/5 male. No other clinical signs were noted thereafter in any animals. Local reactions were recorded at the injection site and consisted in very slight to well-defined erythema, dryness and/or desquamation and scabs. 

Body weight of animals was unaffected by the test item treatment.There were no macroscopic findings at necropsy.

In conclusion, the dermal LD0 of the test item was higher than 2000 mg/kg in rats.

Justification for classification or non-classification

Based on the available data, no classification for acute toxicity is required for 3,3,5 -trimethylcyclohexyl-methacrylate according to the Regulation EC n°1272/2008.