Cyclododeca-1,5,9-triene

Endpoint summary

Description of key information

Oral

1983: According to OECD 401; non-GLP; 5 Wistar rats/sex/dose; 1250, 3980, 4495, 5010 mg/kg bw; mortality observed (K1)

Inhalation

1965: No data on used guideline; non-GLP; at least 10 male Sprague Dawley rats/dose; 5, 6, 7, 8, 8.5, 9, and 10 mg/l; LC50 8.2 mg/l (K1)

Kinematic viscosity at 40°C: 3.63 mm²/s

Dermal

1976: No guideline followed; GLP not specified; 2 Sprague Dawley/sex/dose; 2, 3, and 4 ml/kg bw; LD50 > 3520 mg/kg bw; no mortality observed (K4)

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:

1982-11-29 to 1982-12-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

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 ORGANISMS: 
- Strain: Bor, WISW (SPF TNO)
- Source: F. Winkelmann, Borchen (Germany)
- Weight at study initiation:    females mean 117 g, males mean 121 g
- Controls: no
Environmental conditions: - Feed: R 10 complete feed for rats (Ssniff, Soest; Germany)
- Water: tap water ad libitum
- Room temperature: 20°C (+/- 1°C)
- Humidity: 60% (+/- 5%)
- Air change: 15 times per hour
-Illumination: 12 hour light/dark rhythm

Route of administration:

oral: gavage

Vehicle:

petrolatum

Details on oral exposure:

ADMINISTRATION: 
- Doses: 1250, 2510, 3980, 4495, 5010 mg/kg
- Doses per time period: single dose
- Volume administered or concentration: 10 ml/kg
- Post dose observation period: 14 days

Doses:

1250; 3980; 4495; 5010 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

EXAMINATIONS:
- Post dose observation period: 14 days
- Clinical signs and mortality: Up to 6 hours after treatment and daily  thereafter
- Body weights: before treatment and on days 1, 7, 14
- Necropsy: Macroscopic in 4 animals per dose group (2 females, 2 males)

Statistics:

Litchfield and Wilcoxon (1949), J. Pharmacol. Exp. Ther. 96, 99

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 400 mg/kg bw

95% CL:

>= 4 150 - <= 4 664

Mortality:

MORTALITY: 
- Number of deaths at each dose:   
 1250 mg/kg, 2510 mg/kg: 0/10   
3980 mg/kg: 1 male, 3 females; within 6-48 hours   
4495 mg/kg: 4 males, 4 females; within 24-36 hours   
5010 mg/kg: all animals within 24 hours

Clinical signs:

other: CLINICAL SIGNS: 30 minutes after application animals showed abnormal  symptoms (restlessness, rough skin, decrease of responsiveness, hunched  posture, diarrhoea, moderate to severe tremors, convulsions, sedation,  prone position. Those animals surviving 

Gross pathology:

NECROPSY FINDINGS: When submitted to autopsy, those animals which died  during the test showed redness of the mucosa of the gut and stomach 
and  an accumulation of liquor. Animals which survived the study showed no  pathological changes.

Other findings:

no other findings

Interpretation of results:

GHS criteria not met

Conclusions:

In a determination of the acute oral toxicity on male and female rats it was found that the LD50 of the test item 1,5,9-cyclododecatriene is
4400 mg/kg of body weight. Under the conditions of this study the acute toxicity of 1,5,9-cyclododecatriene afer oral application in rats is very low.

Executive summary:

In a determination of the acute oral toxicity on male and female rats it was found that the LD50 of the test item 1,5,9-cyclododecatriene is 4400 mg/kg bw. 30 minutes after application animals showed restlessness, rough skin, decrease of responsiveness, hunched   posture, diarrhoea, moderate to severe  tremors, convulsions, sedation,  prone position. Those animals surviving the test appeared normal after 5  days at the latest. There was practically no influence on the increase in body weight. Dissection at the end of the experiment revealed redness of the mucosa of the gut and stomach and an accumulation of liquor. Animals which survived the study showed no pathological changes. Under the conditions of this study the acute toxicity of 1,5,9-cyclododecatriene afer oral application in rats is very low.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Method: see reference

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl:CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Strain: Crl:CD
- Controls: no

Route of administration:

inhalation: mist

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

ADMINISTRATION: 
- Type of exposure: whole body
- Concentrations: 5; 6; 7; 8; 8.5; 9; 10 mg/l (nominal)
- Particle size: no data
- Type or preparation of particles: spray nozzle with precision liquid  metering pump
- Post observation period: 14 days

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

6 h

Concentrations:

5; 6; 7; 8; 8.5; 9; 10 mg/l (nominal)

No. of animals per sex per dose:

10 (except 8 mg/l and 10 mg/l: 20 per group)

Control animals:

no

Details on study design:

EXAMINATIONS:    
- throughout exposure period: Clinical signs and mortality 
- 14 day recovery: Body weights examined and gross autopsy of all animals

Statistics:

LC 50 and 95% confidence interval calculated statistically

Sex:

male

Dose descriptor:

LC50

Effect level:

8.2 mg/L air

95% CL:

>= 7.5 - <= 8.9

Exp. duration:

6 h

Mortality:

MORTALITY: 
- Time of death: 92 % during exposure (8% latent mortality)
- Number of deaths at each dose:    
mg/l: 5.0; 6.0; 7.0; 8.0; 8.5; 9.0; 10.0   
dead:   0/10; 1/10; 5/10; 5/20; 4/10; 3/10; 18/20

Clinical signs:

other: MAJOR CLINICAL SIGNS: gasping, twitching, and severe muscle spasms, tonic convulsions.  In  general, recovery of the animals was complete by the third day following  exposure.

Gross pathology:

MAJOR NECROPSY FINDINGS: Distention of all or portions of the gastrointestional  tracts and cyanosis of the exposed body surfaces were the major gross findings at autospsy of the animals which died. Gross appearance of the  organs of the surviving animals was normal.

  
  

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study it is concluded that the LC50 for male rats is 8.2 mg/l (95% confidence interval = 7.5 - 8.9) mg/l for the test item 1,5,9-cyclododecatriene.

Executive summary:

Male rats were exposed whole body for a single, 6 hour periode to vapors of the test item 1,5,9-cyclododecatriene in air at chamber vapor concentrations of 5.0, 6.0, 7.0, 8.0, 8.5, 9.0 and10.0 mg/l. Mortality was 0/10; 1/10; 5/10; 5/20; 4/10; 3/10; 18/20 within the exposure groups (5.0, 6.0, 7.0, 8.0, 8.5, 9.0 and10.0 mg/l) and 92 % died during exposure.

Clinical signs noted in rats from all exposures included gasping, twitching, and severe muscle spasms. In  general, recovery of the animals was complete by the third day following  exposure. Under the conditions of the study it is concluded that the LC50 for male rats is 8.2 mg/l (95% confidence interval = 7.5 - 8.9) mg/l for the test item 1,5,9-cyclododecatriene.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

8 200 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Principles of method if other than guideline:

Method: Noakes DW and Sanderson DM (1969). Brit. J. Ind. Med. 26, 59-64.

GLP compliance:

not specified

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:

age: 12-13 weeks
- housed individually over the 24-hour exposure period, during which time they were deprived of food, but allowed water ad libitum. After exposur the rats were then housed 3/cage (genders separate)

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

ADMINISTRATION:

- Occlusion: yes
- Doses: 2, 3, or 4 ml/kg bw
-test substance was placed onto the shorn dorso-lumbar skin, and bandaged to contact the skin using an impermeable dressing of aluminum foil and waterproof plaster.
- Removal of test substance: washing with a tepid dilute detergent  solution after 24 hours

Duration of exposure:

24 h

Doses:

2, 3, or 4 ml/kg bw

No. of animals per sex per dose:

2 rats of each sex per dose

Control animals:

no

Details on study design:

-observed for signs of intoxication during the following 9 days after exposure

Statistics:

no information

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 520 mg/kg bw

Mortality:

no mortalities

Clinical signs:

other: All animals were seen to have eschar at the application  site on removal of the occlusive dressing.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

3 520 mg/kg bw

Additional information

Oral

Two oral acute toxicity studies are available. The first was conducted in 1961 using 5 Sprague Dawley rats per sex per dose. No data on which guideline was followed was available and the study was performed not in compliance with GLP (pre-GLP). The standard acute test method (no limit test) was used. Male and female rats were treated with 1, 2, 3, 4, and 5 ml/kg bw of the test substance orally by gavage. The vehicle was not specified. The post dose observation period was 14 days. Mortality was observed within 12 hours to four days post treatment with the majority of deaths occurring within 48 hours. At 1, 2, 3, 4, and 5 ml/kg bw, 20%, 20%, 60%, 80%, and 100% died, respectively. Gross pathology revealed gastrointestinal inflammation (especially of the small  intestine), pulmonary congestion, and liver discoloration. The LD50 was concluded to be 2500 mg/kg bw (1961, K4).

The second study was performed using 5 male and female Wistar rats per sex per dose. The standard acute test method (no limit test) was chosen according to OECD 401, not in compliance with GLP. Male and female rats were exposed once orally by gavage to 1250, 2510, 3980, 4495, and 5010 mg/kg bw of the test substance. The vehicle was petrolatum. No control animals were included. Animals received a volume of 10 ml/kg. The post dose observation period was 14 days. In the two lowest dose groups, 1250 and 2510 mg/kg bw, no animals died (0/10). At 3980 mg/kg bw, one male and three females died within 6 -48 hours. At 4495 mg/kg bw, four males and four females died within 24 -36 hours and at the highest dose, 5010 mg/kg bw, all animals died within 24 hours. Thirty minutes after application animals showed abnormal symptoms, such as restlessness, rough skin, decrease of responsiveness, hunched posture, diarrhoea, moderate to severe tremors, convulsions, sedation, and prone position. Those animals surviving the test appeared normal after 5 days at the latest. When submitted to autopsy, those animals which died during the test showed redness of the mucosa of the gut and stomach and an accumulation of liquor. Animals which survived the study showed no pathological changes. Under the conditions of this study, the acute toxicity of the test substance after oral application in rats is very low. The LD50 was concluded to be 4400 mg/kg bw with a 95% confidence interval of >= 4150 <= 4664 mg/kg bw (1983, K1).

Inhalation

Two acute inhalation studies are available for the test substance. The first performed a standard acute method (no limit test) using ten male Sprague Dawley rats in exposure groups 5, 6, 7, 8.5, and 9 mg/l and 20 male rats in groups 8 and 10 mg/l. No specified guideline was followed and the study was non-GLP (pre-GLP). Animals were exposed whole body for a single, 6 -hour period to vapors of the test item in air chamber. Mortality observed in exposure groups 5, 6, 7, 8, 8.5, 9, and 10 mg/l were 0/10, 1/10, 5/10, 5/20, 4/10, 3/10, and 18/20, respectively. Ninety-two percent died during exposure. Clinical signs noted in rats from all exposure groups included gasping, twitching, and severe muscle spasms. In general, recovery of the animals was complete by the third day following exposure. Under the conditions of the study, it was concluded that the LC50 for male rats is 8.2 mg/l (95% confidence interval: 7.5 - 8.9 mg/l) for the test substance (1965, K1).

The second study also performed a standard acute method (no imit test) using six male Sprague Dawley rats per dose. No data was given on used guideline and it was performed non-GLP. Two groups of male rats were exposed nose-only for a single, 4 -hour period to vapors (aerosol) of the test substance in air at chamber vapor concentrations of 6.1 or 8.1 mg/l. The particle size was 2.8 -2.9 µm of mass median aerodynamic diameter (MMAD). One male died during 8.1 mg/l exposure. During the exposures, rats exhibited diminished or no response to sound stimulus. Clinial signs noted in rats from both exposures included ocular and nasal discharges, irregular respiration, abnormal gait or morbidity, and tremors. Additionally, rats exposed to 8.1 mg/l exhibited aggressive behavior and vocalization. Tremors were observed only on test day 1 in both groups. Abnormal gait or morbidity was observed only on test day 1 in rats exposed to 6.1 mg/l and up to 3 days following exposure in rats exposed to 8.1 mg/l. No clinical signs of toxicity were observed after day 4 following exposure. Body weight showed slight to moderate weight losses following exposure. Rats began gaining weight subsequently and did not experience weight loss throughout the remainder of the recovery period. Thus, it was concluded that the LC50 for male rats is greater than 8.1 mg/l air for the test substance (1996, K1).

Dermal

The test method was chosen according to Noakes DW and Sanderson DM (1969). A standard acute method (no limit test) was performed using two Sprague Dawley rats of each sex per dose. Doses of 2, 3, or 4 ml/kg bw were chosen. The unchanged test substance was applied to the skin of rats and covered occlusively. Duration of exposure was 24 h. No control animals were included. An observation period following application was set to 9 days. No animal died during the study period and all animals were seen to have eschar at the application site on removal of the occlusive dressing. The LD50 was concluded to be greater than 3520 mg/kg bw under the conditions chosen (1976, K4).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral, dermal or inhalation toxicity under Regulation (EC) No. 1272/2008.

The test substance is a hydrocarbon and has a kinematic viscosity of 3.63 mm²/s at 40°C. According to Regulation (EC) 1272/2008, the test substance is classified for aspiration toxicity category 1.