cis-2-tert-butylcyclohexyl acetate

Endpoint summary

Description of key information

Acute oral toxicity: a study similar to OECD TG 401: LD50 = 4600 mg/kg bw (95% CI = 2700-7800)

Acute inhalation toxicity LC50 route to route extrapolation = 11960 mg/m3

Acute dermal toxicity: a study similar to OECDTG402: 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:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

1.31, 3.2, 5.0 and 6.5 g/kg bw

No. of animals per sex per dose:

10 / dose, sex unknown

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observation: at 1-4 hours, afterwards daily
- Necropsy of survivors performed: not clear from report

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

4 600 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 700 - <= 7 800

Mortality:

1 animal died on day 7 in the group dosed with 1.31 g/kg bw; 5 animals died on the first day in the group dosed with 3.2 g/kg bw; 4 animals died on day 1 and 2 on day 2 in the group dosed with 5.0 g/kg bw and 3 animals died on day 1 and 1 on day 2 in the group dosed with 6.5 g/kg bw.

Clinical signs:

other: No symptoms were observed in rats dosed with 1.31 g/kg bw. In the group dosed with 3.2 g/kg bw, ataxia was observed in half of the animals, piloerection in 2-3 animals. In the group dosed with 5.0 g/kg bw, lethargy and tetanic convulsion were observed at

Gross pathology:

Very dark lungs were observed in 5 rats of 3.2 g/kg bw group; in 6 rats of 5.0 g/kg bw group and in 4 rats of 6.5 g/kg bw group. Very red stomach was observed in 1 rat from 3.2 g/kg bw group, 3 rats from 5.0 g/kg bw group and 1 rat from 6.5 g/kg bw group. Very red small intesting was found in 4 rats from 3.2 g/kg bw group, 5 rats from 5.0 g/kg bw group, and 1 rat from 6.5 g/kg bw group. Blood around nose and mouth was observed in 5 rats from 3.2 g/kg bw group, 2 rats from 5.0 g/kg bw group, and 4 rats from 6.5 g/kg bw group.

Interpretation of results:

other: Not acute harmful

Remarks:

in accordance with EU CLP (1272/2008 and its updates)

Conclusions:

A LD50 of 4600 mg/kg bw (95% CI = 2700-7800) was obtained in the acute oral toxicity study with rats.

Executive summary:

In an acute oral toxicity study with rats, similar to OECD TG 401 but without GLP, the LD50 was 4600 mg/kg bw (95% CI - 2700 -7800). Groups of 10 animals (sex, strain and age unspecified) were dosed with 1.3, 3.2, 5.0 and 6.5 g/kg bw and observed for 14 days. The numbers of animals that died were 1 at 1.31 g/kg bw, 5 at 3.2 g/kg bw, 6 at 5.0 g/kg bw, and 4 at 6.5 g/kg bw. Clinical findings included ataxia, piloerection, lethargy, convulsions and ptosis. Necropsy findings included very dark lungs, very red stomach and small intestines, and blood around the nose and mouth.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The information is sufficiently adequate and is based on a well conducted, similar to OECD guideline 401, study with a Klimisch 2 code

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:

other:

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

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Duration of exposure:

No data.

Doses:

5.0 g/kg bw

No. of animals per sex per dose:

10/dose; sex unknown

Control animals:

no

Details on study design:

- Necropsy of survivors performed: not clear from report
- Other examinations performed: skin irritation (time/frequency of observations not reported)

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Diarrhea was observed in 1 animal.

Other findings:

Skin irritation: Slight redness in 6 animals, moderate redness in 4 animals; slight edema in 3 animals, moderate edema in 7 animals.

Interpretation of results:

other: Not acute harmful

Remarks:

in accordance with EU CLP (1272/2008 and its updates)

Conclusions:

A LD50 > 5000 mg/kg bw was established in an acute dermal toxicity study with rabbits.

Executive summary:

In an acute dermal toxicity study with rabbits, similar to OECD TG 402 but non-GLP, the LD50 was greater than 5000 mg/kg bw. A group of 10 animals (strain, sex and age unspecified) received a single application of 5000 mg/kg bw test substance. There were no deaths. Diarrhea was observed in one animal. Skin irritation findings included erythema (slight in 6 animals, moderate in 4 animals) and edema (slight in 3 animals, moderate in 7 animals).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The information is sufficiently adequate and is based on a well conducted, similar to OECD guideline 403, study with a Klimisch 2 code.

Additional information

Acute oral toxicity

In an acute oral toxicity study with rats, predating OECD guidelines and GLP (MB Research Laboratories, 1976), the LD50 was 4600 mg/kg bw (95% CI - 2700 -7800). Groups of 10 animals (sex, strain and age unspecified) were dosed with 1.3, 3.2, 5.0 and 6.5 g/kg bw and observed for 14 days. The numbers of animals that died were 1 at 1.31 g/kg bw, 5 at 3.2 g/kg bw, 6 at 5.0 g/kg bw, and 4 at 6.5 g/kg bw. Clinical findings included ataxia, piloerection, lethargy, convulsions and ptosis.Necropsy findings included very dark lungs, very red stomach and small intestines, and blood around the nose and mouth.

Acute dermal toxicity

In an acute dermal toxicity study with rabbits, predating OECD guidelines and GLP (MB Research Laboratories, 1976), the LD50 was greater than 5000 mg/kg bw. A group of 10 animals (strain, sex and age unspecified) received a single application of 5000 mg/kg bw test substance. There were no deaths. Diarrhea was observed in one animal. Skin irritation findings included erythema (slight in 6 animals, moderate in 4 animals) and edema (slight in 3 animals, moderate in 7 animals).

Acute inhalation toxicity

The acute inhalation toxicity can be derived using route to route extrapolation using ECHA CLP guidance, 2017, page 250, 3.1.3.3.5: 1 mg/kg bw = 0.0052 mg/l (5.2 mg/m3. The LD50 of Verdox is 4600 mg/kg bw and this value can be converted to 11960 mg/m3, taking into account that the absorption for the inhalation route can be twice as high as for the oral route (based on default absorption values mentioned in REACH guidance R.8.4.2). The maximum saturated vapour concentration for this substance in mg/m3 is (9.72 Pa x 198000 MW (mg/Mol)) /(8.3 (R, gas constant) x 296°K) = 783 mg/m3. The calculated LC50 value of 11960 mg/m3 cannot be reached because of the saturated vapour concentration of Verdox of 783 mg/m3.

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 CLP (EC No. 1272/2008 and its updates).