Bis(2,3-epoxypropyl) cyclohex-4-ene-1,2-dicarboxylate

Endpoint summary

Description of key information

OECD 401: The acute oral LD50 of the test item in rats of both sexes observed over a period of 14 days is 2938 (2453-3518) mg/kg .

OECD 402: The acute dermal LD50 of the test item in rats of both sexes observed over a period of 14 days is greater than 4600 mg/kg.

Acute inhalation toxicty study was waived as acute toxicity studies are available for the oral and dermal routes of exposure and because of the low Vapor pressure.

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:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf (SPF) strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals
Healthy random bred rats of the Tif: RAIf (SPF) strain raised on our premises were used for these experiments.
They were kept at a room temperature of 22 + 1 °C, at a relative humidity of 55 + 5 % and on a 10 hours light cycle day. They received ad libitum rat food - NAFAG, Gossau SG - and water. Prior to treatment the animals were adapted to our laboratories for a
minimum of 4 days and the initial body weight ranged from 160 to 180 grams.

Route of administration:

other: Oral intubation

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The test item was diluted with carboxymethyl-cellulose 2 %.

Treatment and observations
During the treatment and observation period the animals were housed in groups of 5 in Macroion cages (type 3).
Animals fasted overnight were treated by oral intubation. Physical condition and rate of deaths were monitored throughout the whole observation period.

Doses:

1000 / 2150 / 3590 / 4640 mg/Kg

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not observed
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, physical conditions

The surviving animals were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.

Statistics:

Not applicable

Preliminary study:

N/A

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 938 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 453 - <= 3 518

Remarks on result:

other: LD 50 including 95 % confidence limits were calculated by the probit analysis method (Goulden A., Methods of Statistical Analysis, John Wiley and Sons, 1960, 3rd printing, pages 404-408).

Mortality:

Please see "Any other information on resultzs incl. tables" field

Clinical signs:

Signs and symptoms
Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur. Sedation became more
accentuated as the dose was increased.

Body weight:

Not observed

Gross pathology:

No substance related gross organ changes were seen.

Other findings:

The surviving animals recovered within 7 to 11 days. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.

Rate of deaths:

				Died within
Dose mg/kg	Concentration % of Formulation	N° of animals		1 hour		24 hours		48 hours		7 days		14 days
		male	female	male	female	male	female	male	female	male	female	male	female
1000	10	5	5	0	0	0	0	0	0	0	0	0	0
2150	20	5	5	0	0	0	2	0	2	0	0	0	2
3590	40	5	5	0	0	4	2	4	2	4	2	4	2
4640	50	5	5	0	0	5	5	5	5	5	5	5	5

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral LD50 of TK 12198 in rats of both sexes observed over a period of 14 days is 2938 (2453-3518) mg/kg* .
*LD 50 including 95 % confidence limits were calculated by the probit analysis method (Goulden A., Methods of Statistical Analysis, John Wiley and Sons, 1960, 3rd printing, pages 404-408).

Executive summary:

In this study, female and male rats ( 5 male and 5 female per dose) were traited with thetest item diluted in carboxymethyl-cellulose.

Rats were traited at 1000/2150/3590 and 4640 mg/kg by oral intubation. The observation period was 14 days.

The surviving animals recovered within 7 to 11 days. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.

Signs and symptoms

Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur. Sedation became more accentuated as the dose was increased.

The surviving animals recovered within 7 to 11 days. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.

Dead and killedAnimals: No substance related gross organ changes were seen.

Rate of death:

				Died within
Dose mg/kg	Concentration % of Formulation	N° of animals		1 hour		24 hours		48 hours		7 days		14 days
		male	female	male	female	male	female	male	female	male	female	male	female
1000	10	5	5	0	0	0	0	0	0	0	0	0	0
2150	20	5	5	0	0	0	2	0	2	0	0	0	2
3590	40	5	5	0	0	4	2	4	2	4	2	4	2
4640	50	5	5	0	0	5	5	5	5	5	5	5	5

The acute oral LD50 of the test item in rats of both sexes observed over a period of 14 days is 2938 (2453-3518) mg/kg* .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 938 mg/kg bw

Quality of whole database:

Only this study is available and study is Klimisch 1.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

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

other:

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:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf (SPF) strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals
Healthy random bred rats of the Tif: RAIf (SPF) strain raised on our premises were used for these experiments.
They were kept at a room temperature of 22 + 1° C, at a relative humidity of 55 + 5 % and on a 10 hours light cycle day. They received ad libitum rat food - NAFAG, Gossau SG - and water. Prior to treatment the animals were adapted to our laboratories for a
minimum of 4 days and the initial body weight ranged from 180 to 200 grams.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Treatment* and observations
During the treatment and observation period the rats were housed individually in Macrolon cages (type 2). Approximately 24 hours before treatment an area on the back of the rats of approximately 60 square cm was shaved with an electric clipper.
For treatment the test material was evenly dispersed on the skin with a syringe and was covered with an occlusive dressing which was fastened around the trunk with an adhesive elastic bandage. After 24 hours the dressing was removed, the skin was
cleaned with lukewarm water and the reaction of the skin was appraised.

*Noakes, D.N. and Sanderson, D.M. A method for determining the dermal toxicity of pesticides, Brit. J. Industr. Med., 26, 59-64, 1969

Duration of exposure:

24 hours

Doses:

3590 and 4640

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no weight observed
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology, signs and symptomes

Statistics:

Not applicable

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 600 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occured during the test

Clinical signs:

Within 24 hours after treatment the rats in all osage groups showed sedation, dyspnoea, curved position and ruffled fur. No local skin irritation was seen.
The animals recovered from systemic symptoms within 8 to 14 days. They were submitted at random to a necropsy at the end of the observation period.

Body weight:

Not observed

Gross pathology:

No substance related gross organ changes were seen.

Other findings:

N/A

Rate of death:

				Died within
	Concentration % of Formulation	N° of animals		1 hour		24 hours		48 hours		7 days		14 days
Dose mg/kg		male	female	male	female	male	female	male	female	male	female	male	female
3590	conc.	5	5	0	0	0	0	0	0	0	0	0	0
4640	conc.	5	5	0	0	0	0	0	0	0	0	0	0
No higher doses were possible

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of the test item in rats of both sexes observed over a period of 14 days is greater than 4600 mg/kg.
The test material has therefore practically no acute toxicity to the rat by this route of administration.

Executive summary:

The acute dermal LD50 of the test item in rats of both sexes observed over a period of 14 days is greater than 4600 mg/kg.

5 male and 5 females per concentrations were treated at 3590 and 4640 mg/kg with the test item unchanged.

The test site was covered with an occlusive dressing during 24 hours and wascleaned with lukewarm water and the reaction of the skin was appraised.

As no mortality occured during the test, animals were necropsied at the end of 14 days observation period

Signs and symptoms

Within 24 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. No local skin irritation was seen.

The animals recovered from systemic symptoms within 8 to 14 days. They were submitted at random to a necropsy at the end of the observation period.

Killed animals: No substance related gross organ changes were seen.

The acute dermal LD50 of the test item in rats of both sexes observed over a period of 14 days is greater than 4600 mg/kg.

The test material has therefore practically no acute toxicity to the rat by this route of administration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 600 mg/kg bw

Quality of whole database:

Only this study is available and study is Klimisch 1.

Additional information

The acute dermal LD50 of the test item in rats of both sexes observed over a period of 14 days is greater than 4600 mg/kg.

The test material has therefore practically no acute toxicity to the rat by this route of administration.

The acute oral LD50 of TK 12198 in rats of both sexes observed over a period of 14 days is 2938 (2453-3518) mg/kg.

Justification for classification or non-classification

- oral toxicity: Based on the above stated assessment of the acute oral toxicity of bis(2-3-epoxypropyl)cyclohex-4-ene-1-2-dicarboxylate the substance does need to be classified as Category 5 according to UN GHS criteria and the test item does not need to be classified according CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.

- dermal toxicity: Based on the above stated assessment of the acute dermal toxicity of bis(2-3-epoxypropyl)cyclohex-4-ene-1-2-dicarboxylate the substance does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and accordingCLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.

- inhalation toxicity: Due to the very low vapour pressure of the substance the inhalation route of exposure is considered to be unlikely (1.1 x1E-4 Pa). Therefore no classification for acute inhalation toxicity is deemed necessary according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHSin the EU. A