Reaction mass of ethyl 2,6,6-trimethylcyclohexa-1,3-diene-1-carboxylate and ethyl 2,6,6-trimethylcyclohexa-2,4-diene-1-carboxylate and ethyl 6,6-dimethyl-2-methylenecyclohex-3-enecarboxylate

Endpoint summary

Description of key information

Oral

Oral LD₅₀ = 5 mL/kg bw (eq. to OECD 401, K, Rel.2, Standard acute Method)

Inhalation

Waiver (exposure considerations)

Dermal

Waiver (study scientifically not necessary)

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:

August 28, 1974-January 1975

Reliability:

1 (reliable without restriction)

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)

Version / remarks:

No guideline available in the report as the test has been performed prior to the OECD guideline. However it conforms to the OECD 401 guideline.

Principles of method if other than guideline:

An approximation of the LD50 was obtained by administering the undiluted test substance to groups of young adult rats (two males and two females) in single dose of 1.0, 2.0, 5.0, 10.0 and 15.0 mL/kg body weight by stomach intubation.

GLP compliance:

no

Remarks:

Pre-GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Albino Wistar derived rats were used as the experimental animals.
- Source: CIVO colony (Centraal Instituut Voor Voedingsonderzoek)
- Age at study initiation: young adult
- Weight at study initiation: not reported

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The undiluted test substance was administrated by stomach intubation to groups of young adult rats (two males and two females).

Doses:

Levels single doses: 1.0, 2.0, 5.0, 10.0 and 15.0 mL/kg body weight.

No. of animals per sex per dose:

2 animals/sex/dose

Control animals:

no

Details on study design:

Each dose was expressed in milliliter per kg in the study.

Preliminary study:

No information reported.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 - < 10 mL/kg bw

Based on:

test mat.

Remarks on result:

other:

Mortality:

1/2 females at 5 mL/Kg bw (25% of mortality), 2/2 males and 2/2 females at 10 and 15 mL/Kg bw (100% of mortality).
See Table 1 below.

Clinical signs:

other: After treatment, the rats which received 10 or 15 mL/kg body weight lost consciousness and died within two to three days. One rat died at day 4. See Table 1 below.

Gross pathology:

No observed.

Table 1. Doses applied and mortality after oral administration of one dose of ethyl saffranate to groups of two male and two female rats.

Dose mL/kg body weight	Mortality
	Number		Percentage (%)
	Males	Females
1.0	0/2	0/2	0
2.0	0/2	0/2	0
5.0	0/2	1/2	25
10.0	2/2	2/2	100
15.0	2/2	2/2	100

 

From this table it is seen that LD₅₀ of ethyl saffranate is between 5.0 and 10.0 mL/kg body weight.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions of this study, the oral administration of ethyl safranate at various levels up to 5.0 mL/kg bw did not result in any major abnormalities. The LD50 of ethyl safranate was found to be between 5.0 and 10 mL/kg bw. However, based on female animals, it was concluded that the LD50 of ethyl safranate was 5.0 mL/kg bw, considering the relative density of the substance. Therefore, the test material is not classified according to the Regulation (EC) No. 1272/2008 (CLP).

Executive summary:

In an acute oral toxicity study equivalent to the OECD test guideline No. 401, two males and two females Wistar rats per dose were given the following undiluted dose level: 1.0, 2.0, 5.0, 10.0 and 15.0 mL/kg body weight.

Mortality and clinical signs were monitored during the study.

 

Death occurred for 1/2 females at 5.0 mL/kg bw (25% of mortality) and for 2/2 males and 2/2 females at 10.0 and 15.0 mL/kg bw (100% of mortality). After treatment, the rats which received 10.0 or 15.0 mL/kg bw lost consciousness and died within two to three days. One rat died at day 4.

Oral LD₅₀ Males/Females = 5.0 mL/kg bw

The LD₅₀ of ethyl safranate was found to be between 5.0 and 10.0 mL/kg bw. Based on female animals, it was concluded that the LD₅₀ of ethyl safranate was 5.0 mL/kg bw. 

 

Therefore, the test material is not classified according to the Regulation (EC) No. 1272/2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

One key study conducted in a method similar to OECD 401 and pre-date GLP is available to address the acute oral toxicity endpoint. The study investigated a range of test material concentrations and it was possible to deduce a substance classfication from the study findings; it was therefore assigned a reliability score of 2 in accordance with Klimisch (1997). Overall the quality of the database if high.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

ORAL

A key study was identified (TNO, 1975, rel. 2), on the basis that it gives a definitive LD₅₀, which can be used for classification and labelling purposes.

 

In the acute oral toxicity study equivalent to the OECD test guideline No. 401, two males and two females Wistar rats per dose were given the following undiluted dose level: 1.0, 2.0, 5.0, 10.0 and 15.0 mL/kg body weight.

Mortality and clinical signs were monitored during the study.

Death occurred for 1/2 females at 5.0 mL/kg bw (25% of mortality) and for 2/2 males and 2/2 females at 10.0 and 15.0 mL/kg bw (100% of mortality). After treatment, the rats which received 10.0 or 15.0 mL/kg bw lost consciousness and died within two to three days. One rat died at day 4.

Oral LD₅₀ Males/Females = 5.0 mL/kg bw

The LD₅₀ of ethyl safranate was found to be between 5.0 and 10.0 mL/kg bw. Based on female animals, it was concluded that the LD₅₀ of ethyl safranate was 5.0 mL/kg bw. 

Therefore, the test material is  not classified according to the Regulation (EC) No. 1272/2008 (CLP).

 

DERMAL

Study scientifically not necessary 

The study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation).

 

INHALATION

Exposure considerations

The study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

 

Self classification:

Acute toxicity (Oral)

With respect to the acute oral toxicity data that are available for the test substance, no classification is required for acute oral toxicity, in accordance with Regulation (EC) No. 1272/2008.

 

Acute toxicity (Dermal)

No data available - waiver

 

Acute toxicity (Inhalation)

No data available - waiver

 

Specific target organ toxicity: single exposure (Oral)

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral).

 

Specific target organ toxicity: single exposure (Dermal)

No data available - waiver

 

Specific target organ toxicity: single exposure (Inhalation)

No data available - waiver

 

Aspiration hazard

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.