4-(1,1-dimethylethyl)cyclohexyl methacrylate

Endpoint summary

Description of key information

Acute oral toxicity for 4 -tert-butylcyclohexyl methacrylate LD50 is considered to be in the range of 2000 -2400 mg/kg bw.

Acute dermal toxicity for 4-tert-butylcyclohexyl methacrylate LD50 is assigned to be > 2000 mg/kg bw (based on cyclohexyl methacrylate, 101 -43 -9 (read across substance)).

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:

Initiation date 15-10-'84 Completion date 29-10-'84

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Purity: >98%
Solubility: ready miscible with ethanol and acetone
Melting point: 12 °C
Specific gravity: 0.945 g/cm^3
Storage: at ambient temperature in the dark

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Fourty young adult rats of the Wistar strain (SPF-quality, randomly bred) were obtained from the Central Institute for the Breeding of Laboratory Animals TNO (CPB), Zeist, The Netherlands. Male body weights of the main study on day 0 ranged from 269 to 284 g and those of the females from 169 to 199 g. Date of arrival at the animal house: October 10, 1984. From that date on, the animals were individually housed in Macrolon cages. They had free access to tap water and standard laboratory animal diet (RMH-B, pellet diameter 10 mm), which was obtained from Hope Farms, Woerden, The Netherlands. The animal room temperature was maintained at 20 ± 1 °C and the relative humidity at 45 and 80 per cent. The artificial light sequence was 12 hours light, 12 hours dark. Feed was withheld overnight before dosing till 4 hours after administration of the test substance.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test substance was administered as such in a single dose using a stomach cannula.

Doses:

Range finding investigation: 1800, 1000, 560 and 320 mg/kg. In addition, 2 males were dosed with 3200 and 2400 mg/kg.
Main study: 2400, 3200 and 4200 mg/kg body weight

No. of animals per sex per dose:

Range finding investigation: 1 male and 1 female per dose. Additional dosage (3200 and 2400 mg/kg): 2 males were dosed.
Main study: 5 males and 5 females per dose

Control animals:

no

Details on study design:

The test substance is administered orally by gavage in graduated doses to several groups of rats, one dose being used per group. Subsequently observations of toxic effects and deaths are recorded. Animals which die during the test and those killed at the end of the 14-day observation period are subjected to autopsy.

Preliminary study:

Each group of one male and one female rat received a single oral dose at a dosage of 1800, 1000, 560 and 320 mg/kg, respectively. In addition two males received a dose of 3200 and 2400 mg/kg, respectively. Both these animals died of convulsions within 20 minutes of dosing. All other animals showed no signs of toxicity. Macroscopic examination at autopsy of animals found dead revealed no gross abnormalities.

Key result

Sex:

male/female

Dose descriptor:

other: Range where high probability of acute toxicity is concluded

Remarks:

Due to the high mortality in the low dose group and absence of deaths in the high dose group calculation of the LD50 value was not appropriate.

Effect level:

>= 2 000 - <= 2 400 mg/kg bw

Based on:

test mat.

Mortality:

The following doses were administered to groups of 5 male and 5 female rats each: 2400, 3200 and 4200 mg/kg body weight. In the low dose group 4 animals died and in the medium dose group one animal; high dose animals survived.
All deaths occurred within 25 minutes of dosing.

Clinical signs:

other: In general, animals showed convulsions shortly prior to death. Surviving animals showed no signs of systemic toxicity.

Gross pathology:

Macroscopic examination of animals found dead and surviving animals at autopsy revealed no test substance related gross abnormalities.

Due to the high mortality in the low dose group and absence of deaths in the high dose group calculation of the LD₅₀ value was not appropriate. Confirmation of this unexpected distribution of deaths was obtained by an earlier study (dose levels 2000, 2400 and 2750 mg/kg) which was aborted due to the somewhat odd, although retrospectively, as it seemed, comparable occurrence of mortality at low doses, i.e. 2000 and 2400 mg/kg (3/10 and 1/10).

Based on the results of both studies a high probability of acute toxicity is concluded in the range from approximately 2000 to 2400 mg/kg body weight.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Three groups of 5 male and 5 female Wistar rats each received a single oral dose of Nourycryl MC 110 at levels of 2400, 3200 and 4200 mg/kg body weight. Seventeen per cent of the animals died. All deaths occurred within 25 minutes of dosing. The majority of deaths were observed in the low dose group; no mortalities occurred in the high dose group. Toxic signs were convulsions shortly prior to death. In comparison to the first week a slightly reduced body weight gain was observed in the second week among female animals. Surviving male animals showed no such reduction. Autopsy of animals found dead and of surviving animals showed no test substance related gross abnormalities. Due to the high mortality in the low dose group and absence of deaths in the high dose group calculation of the LD50 value was not appropriate. This unexpected distribution of deaths was confirmed by an earlier, not completed study which also showed mortality at low doses (2000 and 2400 mg/kg) . Based on the results of both studies a high probability of acute toxicity is concluded in the range from approximately 2000 to 2400 mg/kg body weight.

Executive summary:

Three groups of 5 male and 5 female Wistar rats each received a single oral dose of Nourycryl MC 110 at levels of 2400, 3200 and 4200 mg/kg body weight. Seventeen per cent of the animals died. All deaths occurred within 25 minutes of dosing. The majority of deaths were observed in the low dose group; no mortalities occurred in the high dose group. Toxic signs were convulsions shortly prior to death. In comparison to the first week a slightly reduced body weight gain was observed in the second week among female animals. Surviving male animals showed no such reduc ion. Autopsy of animals found dead and of surviving animals showed no test substance related gross abnormalities. Due to the high mortality in the low dose group and absence of deaths in the high dose group calculation of the LD₅₀ value was not appropriate. This unexpected distribution of deaths was confirmed by an earlier, not completed study which also showed mortality at low doses (2000 and 2400 mg/kg) . Based on the results of both studies a high probability of acute toxicity is concluded in the range from approximately 2000 to 2400 mg/kg body weight. GHS Category 5 was assinged for classification purposes. It is not classified according to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures (2015).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

reliable

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

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

other:

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

see attached Read Across rationale

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report):Cyclohexylmethacrylate
- Physical state: liquid
- Analytical purity: 99.27 %

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld (Germany)
- Age at study initiation: young adult animals ( male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation: animals of comparable weight ( +/- 20 % of the mean weight)
- Housing: single housing
- Diet (e.g. ad libitum): ad libitum ( VRF1(P); SDS Special Diets Services, Altrip, Germany)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 40 cm²
- % coverage: 10 %
- Type of wrap if used: semi occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

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: weekly
- Other examinations performed: clinical signs

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Systemic effects: No systemic clinical signs were observed during clinical examination. Local effects: No local effects were observed.

Gross pathology:

No macrosopic pathologic abnomalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Mortality
Dose (mg/kg bw):	2000	2000
Sex:	Male	Female
Administration:	1	1
No. of animals:	5	5
Mortality (animals):	No mortality	No mortality

 

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of 101-43-9 is > 2000 mg/kg bw.

Executive summary:

The dermal LD50 of 101-43-9 is > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

reliable

Justification for classification or non-classification

The substance is not classified according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures. Data are considered conclusive but not sufficient for classification.