Acid Catalysed Reaction Products of 3,7-dimethyl-2,6-octadienal in the presence of ethanol

Endpoint summary

Description of key information

In an acute oral toxicity study in female rats, conducted in accordance with OECD 423 (2001) and according to GLP principles, a LD50 oral of >2000 mg/kg bw was determined. In an acute dermal toxicity study with 10 rabbits, performed equivalent to OECD 402 (1981), a LD50 of >5000 mg/kg bw was determined.

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:

October 16, 2012 - November 15, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(2001)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(2008)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Identification: Citrathal
Description: Clear yellow liquid
Batch: SC00005944
Storage conditions: room temperature in the dark

Species:

rat

Strain:

other: Wistar (RccHan:WIST)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 154-176 g
- Fasting period before study: overnight before dosing
- Housing: Group housing of 3 animals per cage in suspended solid-floor polypropylene cages
- Diet: Free access (2014C Teklad Global Rodent diet, Harlan Laboratories UK Ltd.)
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

GAVAGE METHOD: metal cannula attached to a graduated syringe
Frequency: single dosage, on Day 1.

DOSE VOLUME APPLIED: 2.18 mL/kg body weight

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

- Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality and Clinical signs: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily
Body weights: prior to dosing and 7 and 14 days thereafter
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortalities and no clinical signs of toxicity occurred

Mortality:

No mortalities occurred

Clinical signs:

No clinical signs of toxicity occurred

Body weight:

No abnormalities were observed

Gross pathology:

No abnormalities were observed

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in female rats, conducted in accordance with OECD 423 (2001) and according to GLP principles, a LD50 oral of >2000 mg/kg bw was determined.

Executive summary:

The acute oral toxicity in female rats has been studied in accordance with OECD 423 (2001), EU Method B.1 tris (2008) and according to GLP principles. The substance was dosed (undiluted) at 2 g/kg bw in 6 female rats, in 2 steps. No mortality and no clinical signs of toxicity occurred. Macroscopic examination of the animals did not reveal any abnormalities. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw. Based on this result, the substance does not need to be classified for acute toxicity by the oral route in accordance with the CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study has Klimisch score 1

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

September, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1981)

Deviations:

yes

Remarks:

lack of the study design and test material details in the report

GLP compliance:

no

Remarks:

(study performed prior to GLP was in place)

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
No data

ENVIRONMENTAL CONDITIONS
No data

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

No data

Duration of exposure:

No data

Doses:

5000 mg/kg

No. of animals per sex per dose:

10 animals (sex unknown)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: no data
- Necropsy of survivors performed: yes

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

1 animal died on day 14

Clinical signs:

Diarrhea, difficulty in walking due to severe skin reaction, lethargy, emaciation, ataxia, yellow nasal discharge, adipsia, anorexia, tachypnea, mucous in stool, respiratory rattle (no data about which clinical sign when was observed in which animal).

Body weight:

No data

Gross pathology:

See section "Any other information on results incl. tables"

Other findings:

- Erythema (redness) (day 1): Moderate in 4 of the 10 animals; Severe in 6 of the 10 animals
- Edema (day 1): Moderate in 10 of the 10 animals

 

Necropsy observations; Number of animals
Normal	3
Exudate, nose/mouth yellow	1
Exudate, anogenital, brown	1
Intestines, areas yellow	1
Intestines, bloated	3
Liver dark	1
Liver, mottled	1
Lungs, areas dark	2
Lungs, bright orange	2
Kidney dark	2
Kidney, mottled	2
Kidney, white nodules	1

 

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study with 10 rabbits, performed equivalent to OECD 402 (1981), a LD50 of >5000 mg/kg bw was determined.

Executive summary:

The substance was tested in an acute dermal toxicity study (limit test) with 10 rabbits, performed equivalent to OECD 402 (1981). One animal died on day 14. Diarrhea, difficulty in walking due to severe skin reaction, lethargy, emaciation, ataxia, yellow nasal discharge, adipsia, anorexia, tachypnea, mucous in stool and respiratory rattle was observed among the animals. Moderate to severe erythema and moderate edema was observed on day 1. Based on the results, a LD50 of >5000 mg/kg bodyweight was determined. Based on this result, the substance does not need to be classified for acute toxicity by the dermal route in accordance with the CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The study has Klimisch score 2

Additional information

Acute toxicity: oral

The acute oral toxicity in female rats has been studied in accordance with OECD 423 (2001), EU Method B.1 tris (2008) and according to GLP principles. The substance was dosed (undiluted) at 2 g/kg bw in 6 female rats, in 2 steps. No mortality and no clinical signs of toxicity occurred. Macroscopic examination of the animals did not reveal any abnormalities. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw.

Acute toxicity: dermal

The substance was tested in an acute dermal toxicity study (limit test) with 10 rabbits, performed equivalent to OECD 402 (1981). One animal died on day 14. Diarrhea, difficulty in walking due to severe skin reaction, lethargy, emaciation, ataxia, yellow nasal discharge, adipsia, anorexia, tachypnea, mucous in stool and respiratory rattle was observed among the animals. Moderate to severe erythema and moderate edema was observed on day 1. Based on the results, a LD50 of >5000 mg/kg bodyweight was determined.

Justification for selection of acute toxicity – oral endpoint
The only study with a reliability of 1 that is available.

Justification for selection of acute toxicity – dermal endpoint
The only available study.

Justification for classification or non-classification

The substance does not need to be classified for acute oral and acute dermal toxicity in accordance with the CLP Regulation as the acute oral toxicity is >2000 mg/kg bw and as the acute dermal toxicity is >5000 mg/kg bw.