4-(1,1-dimethylethyl)cyclohexyl acrylate

Endpoint summary

Description of key information

Oral LD50 approx. 5000 mg/kg bw (BASF, 1982)

Dermal: LD50 > 2000mg/kg (BASF 2015), no mortality

 

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:

1981-07-14 to 1981-07-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

according to BASF-internal standard

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River WIGA, Sulzfeld, FRG
- Age at study initiation: about 12 weeks
- Weight at study initiation: males: 200-230 g; females: 180-190 g
- Fasting period before study: yes, 16 hours
- Housing: 5 animals per cage (DK-III stainless steel wire mesh cages)
- Diet: ad libitum SSNIFF R (Ssniff Versuchstierdiäten, Soest, FRG)
- Water: ad libitum (fully demineralized water each workday and tap water on public holidays)
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): 45 - 75
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 43 % w/v (2150 mg/kg); 50 % w/v (5000 mg/kg)
- Amount of vehicle: 5 and 10 mL/kg
- Justification for choice of vehicle: Test substance not soluble in water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2150 and 5000 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: weighing was conducted on study days 1, 2, 3, 7 and 13; Recording of signs and symptoms < 15 min, 15 min, 30 min , 1 h, 2 h, 4 h, and 5 h after administration of test substance and then once each workday
- Necropsy of survivors performed: yes
- examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

ca. 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were observed at 2150 mg/kg bw. At 5000 mg/kg bw 4 animals died during the course of the study.

Clinical signs:

other: At 2150 mg/kg bw both male and females rats showed a poor general state during the first two days. Dyspnea, apathy, staggering and piloerection lasted up to study day 3. At 5000 mg/kg bw a poor general state was observed in males during the first two days

Gross pathology:

Animals that died during the study showed acute dilatation of the atria, acute congestion and lung emphysema. Sacrificed animals did not show any gross internal lesions.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

well-documented, scientifically acceptable study report

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1981-08-04 to 1981-08-20

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

Based on substance loss (by weight) the concentration was app. 0.1 mg/L, but the calculated saturated vapour concentration is 51.7 mg/L

Principles of method if other than guideline:

The test was performed in principle as described in OECD test guideline 403. It demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at 20 °C. Young adult laboratory rats, 3 per sex, were exposed sequentially to the vapors generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 7 h. The exposure was subsequently repeated in the same manner. No analytical determination of the atmosphere concentrations was performed. Group-wise documentation of clinical signs was performed over a 14 day study period. Afterwards, the animals were killed and examined by gross pathology. The nominal concentration was calculated as quotient of the amount of test substance weight loss during exposure, and the amount of air used during exposure.

GLP compliance:

no

Test type:

other: Inhalation hazard test

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wiga, Sulzfeld, FRG
- Age at study initiation: 7 - 10 weeks
- Weight at study initiation: males: 180 - 250 g; females: 180 - 250 g
- Fasting period before study: no
- Housing: groups of 3 animals per sex (Wire cage (Becker, D III))
- Diet: ad libitum, Herilan MRH (EGGERSMANN KG, Rinteln, FRG) in the form of pellets
- Water: ad libitum, tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The product was introduced to a height of 5 cm into a glass bottle (generator) with a sintered glass disk (pore-size 90 - 150 µm, diameter 30 mm), and the weight was determined.
The generator containing the product was placed in a water bath maintained at 20 °C by a thermostat, and a stream of 200 L/h compressed air was supplied to a downstream mixing chamber. The mixture of air and test substance generated in this way was passed through a glass distributor to 6 glass tubes in which 3 male and 3 female animals had been placed. The emerging mixtures of test substance and air were exhausted.
The temperature in the exposure apparatus was between 19 and 25 °C. After 30 minutes, the generator was replaced by a new one containing fresh test substance as described above. This generator was then used for the remainder of the test.

Determination of the nominal concentration:
The amount of test substance used was determined by reweighing the generators. The nominal concentration was calculated from the amount of test substance consumed and the air volume.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

7 h

Concentrations:

0.86 mg/L

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: clinical examinations each work day and lethality each day.
- Necropsy of survivors performed: yes (gross pathology)

Key result

Sex:

male/female

Dose descriptor:

other: IHT

Remarks on result:

other: No mortality was observed after 7 h exposure

Mortality:

No mortality was observed.

Clinical signs:

other: Restlessness was observed during exposure. No clinical signs were observed after exposure and during the post exposure observation period.

Gross pathology:

No pathological findings were noted.

Interpretation of results:

study cannot be used for classification

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, 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, Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): approx. 10
- 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: The test item was covered with an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: after 24 hour

Duration of exposure:

24 h

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
- Other examinations performed: clinical signs, body weight, pathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed fpr male or female animals during clinical examination. Moderate erythema (grade 3) was noted in all male animals on study day 1. Erythema decreased to well-defined erythema (grade 2) in all animals on study day 2,

Gross pathology:

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

Under the conditions of this study the median lethal dose (LD50) of Laromer TBCH after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute Oral Toxicity

In an acute oral toxicity study similar to OECD 401, groups (5/sex) of Sprague-Dawley rats (about 12 weeks old) were administered with a single oral dose (gavage) of the test substance emulsified in olive oil at concentrations of 2150 and 5000 mg/kg bw. Animals were then observed for 14 days (BASF, 1982). No mortality was observed at 2150 mg/kg bw. 4 animals died in the 5000 mg/kg bw dosing group. Clinical signs that were observed at 2150 mg /kg bw included a poor general state during the first two days for male and female animals. Dyspnea, apathy, staggering and piloerection lasted up to study day 3. At 5000 mg/kg bw a poor general state was observed in males during the first two days. Females showed a poor general state until the end of the study period. Dyspnea and piloerection lasted up to study day 6 in male rats. Females showed dyspnoe until study termination. Both exhibited apathy, staggering, trembling, spastic gait, exsicchosis and cachexia up to study day 2. Aggressiveness was observed up to study day 9 in females only. Animals that died during the study showed acute dilatation of the atria, acute congestion and lung emphysema. Sacrificed animals did not show any gross internal lesions. An LD50 of approx. 5000 mg/kg bw was determined for both male and female animals.

Acute Inhalation toxicity

Six rats (3 males and 3 females) were exposed for 7 hours to a vapour saturated atmosphere in an inhalation risk test (BASF 1982). No mortality was observed. Animals were restless during exposure. No clinical signs were observed in the post-exposure period. No pathological changes were observed at necropsy. Based on substance loss determined by weighing, the concentration in the chamber was estimated as 0.1 mg/L. Based on the vapour pressure of the substance, the concentration in a saturated atmosphere is calculated to be 51.7 mg/L. The reason for this difference is not clear. Thus the results cannot be assessed.

Acute dermal toxicity

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test substance to the clipped skin and covered by semi-occlusive dressing for 24 hours (BASF 2015). The animals were observed for 14 days. No mortality occurred and no signs of systemic toxicity were observed. Very slight to moderate erythema and edema were observed that regressed within the study perios. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data the test item is not classified for acute oral and dermal toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.