Reaction mass of 3,7-dimethyl-1-octyl acetate and citronellyl acetate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

acceptable data, no GLP, TS purity not specified

Justification for type of information:

This information is used for read-across to Citronellyl Acetate Multi.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

acceptable data, no GLP, TS purity not specified

Justification for type of information:

This information is used for read-across to Citronellyl Acetate Multi

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

acute oral toxicity study

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
- Fasting period before study: 16 h

TEST ANIMALS
- Weight at study initiation: 150 - 208 g
- Acclimation period: 5 d before beginning of study
- Housing: stock cages
- Housing after dosing:  individually in wire-mesh cages
- Food and water: ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

3000, 4600, 6800, 10200 mg/kg bw

No. of animals per sex per dose:

2 male and 2 female per dose

Control animals:

other: not applicable

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, initial and final body weight

Statistics:

Weil and Thompson methods

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 800 mg/kg bw

Remarks on result:

other: Standard deviation: ± 800 mg/kg bw

Mortality:

3000 mg/kg bw: 0/4 deaths
4600 mg/kg bw: 0/4 deaths
6800 mg/kg bw: 2/4 deaths
10200 mg/kg bw: 4/4 deaths

Clinical signs:

other: 3000 mg/kg: hypoactivity, ruffed fur 4600 mg/kg bw: hypoactivity, ruffed fur, muscular weakness 6800 mg/kg bw: hypoactivity, muscular weakness, prostration, diarrhea, ruffed fur 10200 mg/kg bw: hypoactivity, muscular weakness, prostration, diarrhea, ruffe

Gross pathology:

Animals sacrificed: no gross findings
Animals found dead: gastroenteritis, pale livers, pale kidneys, hemorrhages in the stomachs

Interpretation of results:

other: Not acutely harmful

Remarks:

according to according to EU CLP (EC No. 1272/2008, and its amendments).

Conclusions:

The oral acute toxicity is 6800 mg/kg bw in male and female rats.

Executive summary:

Oral acute toxicity data are available from a study comparable to guideline (OECD 401) with acceptable restrictions. In this study 2 animals/sex were administered doses of 3000, 4600, 6800, and 10200 mg/kg bw via gavage (no vehicle) and observed for 14 days. Observations included mortality, clinical signs, and initial and final body weights. At the end of the study, necropsy of survivors was performed. At doses of 6800 and 10200 mg/kg bw, mortality was 50% and 100%, respectively. At low doses hypoactivity and ruffed fur was recorded, at higher doses symptoms included also muscular weakness, prostration, and diarrhoea. No evident effect on body weights was observed in survivors. Post-mortem necropsy of survivors revealed no gross pathology. Animals found dead during the test showed gastroenteritis, pale livers, pale kidneys, and haemorrhages in the stomachs. Based on these findings, the acute oral LD50 is 6800 mg/kg bw.

Cross-reference 2

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across information.

Justification for type of information:

The read-across justification is presented in the Endpoint summary Acute toxicity. The accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: read-across from Citronellyl Acetate ('mono')

Interpretation of results:

other: Not acute harmful

Remarks:

according to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

The dermal acute toxicity is >2000 mg/kg bw in male and female rats, based on the results of the source substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1971

Report date:

1971

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

acute dermal toxicity study

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Citronellyl acetate

EC Number:

205-775-0

EC Name:

Citronellyl acetate

Cas Number:

150-84-5

Molecular formula:

C12H22O2

IUPAC Name:

3,7-dimethyloct-6-en-1-yl acetate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 – 3.1 kg
- Observation period before study: 7 d
- Housing: individually in hanging rabbit cages
- Food and water: ad libitum

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 24 h before the dermal applications: an area on the backs of the animals was shaved (ca. 30% of total body surface), animals were returned to the cages to allow the stratum corneum to recover
- Type of wrap: impervious plastic secured with tape

TEST MATERIAL
- Concentration (if solution): undiluted test material
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, initial and final body weight, behavioral abnormalities, skin reactions

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

0/4 deaths

Clinical signs:

other: no effects; no behavioral abnormalities

Gross pathology:

no gross findings at necropsy

Other findings:

Local skin reactions:
after 24 h: irritant effects - definite red erythema, mild edema
after 6 d: superficial escharosis
end of the 14-day observation period: sloughing

Applicant's summary and conclusion

Interpretation of results:

other: Not acutely harmful

Remarks:

according to EU CLP (EC No. 1272/2008, and its amendments).

Conclusions:

The dermal acute LD50 is >2000 mg/kg bw in male and female rats.

Executive summary:

Dermal acute toxicity data are available from a study comparable to guideline (OECD 402) with acceptable restrictions (Reliability 2). In this study 2 rabbits/sex were administered a single dose of 2000 mg/kg bw (undiluted test material) on shaved skin wrapped in an occlusive material. Exposure duration was 24 hours and was followed by a 14-day observation period. Examinations included, mortality, initial and final body weight, behavioural abnormalities, and skin reactions. Necropsy of animals found dead during the test and of survivors was performed. No mortality or other signs of toxicity were observed throughout the test. Local skin reactions included definite red erythema and mild edema after 24 h, superficial escharosis after 6 days, and sloughing at end of the 14-day observation period. Based on these findings, the acute dermal LD50 is >2000 mg/kg bw in male and female rats.