4-(1-methoxy-1-methylethyl)-1-methylcyclohexene

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 5000 mg/kg bw
Acute inhalation toxicity: Extrapolated from acute oral toxicity LC50 > 13000 mg/m3
Acute dermal toxicity: Extrapolation from acute oral toxicity: LD50 > 5000 mg/kg bw

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:

3 October, 1983 - 24 October, 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Five rats per sex per dose were exposed to the test substance via oral gavage. They were exposed to 3200, 4000, 5000 mg/kg bw. After an observation period of 14 days animals were necropsied.

GLP compliance:

yes

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 Breeding Laboratories, Wilmington, Massachusetts, USA
- Weight at study initiation: 180 – 280 (after fasting)
- Fasting period before study: 18 hours
- Housing: individually, in stainless steel wire mesh cages,
- Diet: Wayne Lab Blox, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 days

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

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

only for 3200 mg/kg bw dosing

Doses:

3200, 4000, 5000 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: animals were observed immediately and at 1, 4 and 24 hours after dosing and twice daily for 14 days. Body weights were recorded on the 14th day.
- Necropsy of survivors performed: yes

Preliminary study:

In a dose-range finding study, 4 fasted animals, 2 per sex, were administered the test article at 500, 1600 and 5000 mg/kg bw, orally by gavage. Signs observed were abnormal gait, abnormal stance, decreased body tone, piloerection, decreased activity, lacrimation, semiprostration, salivation, poor grooming and prostration. None of the animals died at the 500 or 1600 mg/kg bw dose levels. 3 of 4 animals died at the 5000 mg/kg bw dose level.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

- 1 out of 5 males and 2 out of 5 females died exposed to 3200 mg/kg bw
- 1 out of 5 males and 2 out of 5 females died exposed to 4000 mg/kg bw
- 1 out of 5 males and 1 out of 5 females died exposed to 5000 mg/kg bw

Clinical signs:

other: Signs observed included decreased activity, abnormal stance, prostration, hypersensitivity, exophthalmos, tremors, semiprostration and dyspnea. One rat was observed with paralysis of both front pays due to self-traumatization.

Gross pathology:

- Necropsy of the animals that died revealed discoloration of the intestines and bladder. Hemorrhages in the stomach, cecum and bladder were observed. Necrotic livers and congested, edematous lungs were also observed.
- Atrophy of the testes was observed upon necropsy of the sacrificed male animals. No test article related lesions were observed in the females that were sacrificed.

Interpretation of results:

other: criteria not met.

Remarks:

according to EU CLP criteria (1272/2008 and its amendments)

Conclusions:

The acute oral toxicity test showed an LD50 of >5000 mg/kg bw

Executive summary:

In an acute oral toxicity test five Sprague-Dawley rats per sex per dose were exposed to the test substance via oral gavage to 3200, 4000, and 5000 mg/kg bw. Signs observed included: decreases activity, salivation, lacrimation, poor grooming, piloerection, decreased body tone, abnormal gait, abnormal stance, prostration, hypersensitivity, exophthalmos, tremors, semiprostration and dyspnea. One rat was observed with paralysis of both front paws due to self-traumatization. Three of ten animals died at the 3200 and 4000 mg/kg bw dose levels and two out of ten died at 5000 mg/kg bw. Necropsy of the animals that died revealed discoloration of the intestines and bladder. Hemorrhages in the stomach, cecum and bladder were observed. Necrotic livers and congested, edematous lungs were also observed. Atrophy of the testes was observed upon necropsy of the sacrificed male animals. No test article related lesions were observed in the females that were sacrificed. The acute oral LD50 for substance in both males, females and combined was determined to be >5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute oral toxicity result is of sufficient quality and adequate for this dossier.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute oral toxicity: In an acute oral toxicity test five Sprague-Dawley rats per sex per dose were exposed to the test substance via oral gavage to 3200, 4000, and 5000 mg/kg bw. Signs observed included: decreases activity, salivation, lacrimation, poor grooming, piloerection, decreased body tone, abnormal gait, abnormal stance, prostration, hypersensitivity, exophthalmos, tremors, semiprostration and dyspnea. One rat was observed with paralysis of both front paws due to self-traumatization. Three of ten animals died at the 3200 and 4000 mg/kg bw dose levels and two out of ten died at 5000 mg/kg bw. Necropsy of the animals that died revealed discoloration of the intestines and bladder. Hemorrhages in the stomach, cecum and bladder were observed. Necrotic livers and congested, edematous lungs were also observed. Atrophy of the testes was observed upon necropsy of the sacrificed male animals. No test article related lesions were observed in the females that were sacrificed. The acute oral LD50 for substance in both males, females and combined was determined to be >5000 mg/kg bw.

Acute dermal toxicity: The acute dermal toxicity is > 5000 mg/kg bw based on LD50 of the oral route, using route to route extrapolation.

An acute inhalation toxicity. For inhalation, an oral LD50 of >5000 mg/kg bw can be converted into an inhalation LC50 > 13000 mg/m3 (using the algorithm 5000 mg/kg bw x 50/100 (oral versus inhalation absorption) x 1000*). The maximum saturates vapour pressure for Orange Flower ether is 685 mg/m3 (9.9 Pa (Vap Pr. Orange Flower ether) x 168 (MW) / 8.3 (R, gas constant) x 293 (°K)). This means that Orange Flower ether cannot reach a concentration higher than 685 mg/m3. Therefore an LC50 for inhalation (calculated to be >13000 mg/m3) cannot be reached and no classification and labelling is needed for the acute inhalation route. *(CLP guidance 2015, page 255).

Justification for classification or non-classification

Based on the available information classification and labelling for acute oral, dermal and inhalation toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and its amendments.