Registration Dossier

Diss Factsheets

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
4-(1,1-dimethylethyl)cyclohexyl methacrylate
EC Number:
256-277-5
EC Name:
4-(1,1-dimethylethyl)cyclohexyl methacrylate
Cas Number:
46729-07-1
Molecular formula:
C14H24O2
IUPAC Name:
4-tert-butylcyclohexyl 2-methylprop-2-enoate
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

Test animals

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.

Administration / exposure

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.

Results and discussion

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.
Effect levels
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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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).