Octa-1,7-diene

Endpoint summary

Description of key information

Oral (OECD 423), rat: LD50 > 2000 mg/kg bw; LD50 cut-off value = 5000 mg/kg bw (limit test)
Inhalation, rat: LC50 > 36 mg/L air  

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted Dec 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted in May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

adopted in Aug 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Freie und Hansestadt Hamburg, Behörde für Soziales, Familie und Verbraucherschutz, Hamburg, Germany

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 172 - 183 g
- Fasting period before study: yes, 16 hours before treatment
- Housing: 3 animals/cage in Makrolon cages type III plus
- Diet: ssniff R/M-H V1534 (ssniff Spezialdiäten GmbH, Soest, Germany)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 24 Feb 2012 To: 21 Mar 2012

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.78 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (3 per step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: before and immediately, 5, 15, 30, 60 min as well as 3, 6, 24 hours after administration, at least once a day thereafter
- Frequency of weighing: before administration and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor acitivity as well as behaviour pattern; clinical signs (tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma), body weight; histopathology was only carried out in case of macroscopical findings

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: According to OECD Guideline 423, Annex 2d, a cut-off value of 5000 mg/kg bw was derived based on a limit test with 2000 mg/kg bw, since no mortality occurred in any step.

Mortality:

No mortality occurred.

Clinical signs:

other: The following clinical signs were observed: slightly reduced motility (30 min - 3 h, 6/6 animals), slight ataxia (30 min - 3 h, 6/6 animals), slightly increased muscle tone (30 min - 3 h, 6/6 animals), salivation (15 min - 3 h, 6/6 animals) and pilo-erect

Gross pathology:

No pathological changes were observed at necropsy.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

No mortality was observed in 2 groups of 3 female rats at the limit dose of 2000 mg/kg bw using the acute-toxic-class method. Thus, the LD50 cut-off value was 5000 mg/kg bw according to OECD Guideline 423.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given

Principles of method if other than guideline:

6 rats were exposed via inhalation (whole body) to the vapour of the test substance at a concentration of 8000 ppm for 4 h followed by a 14-day observation period. Addionally, rats were exposed to an atmosphere saturated with vapour of the test substance for different time periods (15 min up to 8 h) in order to determine the longest inhalation period which permitted all rats to survive the 2-week observation period.

GLP compliance:

no

Remarks:

study performed prior to implementation of GLP

Test type:

standard acute method

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION (concentrated vapour inhalation)
- Exposure apparatus: sealed chamber
- Exposure chamber volume: 120 L
- Source and rate of air: passing 2.5 L/min of dried air through a fritted glass disc immersed to a depth of at least 2.54 cm in approx. 50 mL of the test substance contained in a gas-washing bottle
- Temperature in air chamber: room temperature

GENERATION OF TEST ATMOSPHERE (inhalation of metered vapour concentration)
- Source and rate of air: flowing stream of vapour prepared by various styles of proportioning pumps

TEST ATMOSPHERE
- Brief description of analytical method used: no analytics performed
- Samples taken from breathing zone: no

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Remarks on duration:

Exposure to 8000 ppm; Additionally, treatments with concentrated vapour were performed for several other time periods (15 min - 8 h).

Concentrations:

Metered vapour concentration: 8000 ppm (corresponding to 36 mg/L)
Saturated vapour concentration at 20 °C: 129.803 mg/L (QSAR; Danish EPA Database, 2004)

No. of animals per sex per dose:

6 animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 36 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 8000 ppm; 2/6 animals died

Mortality:

2/6 animals died by inhalation of the metered vapour concentration of 8000 ppm with an exposure duration of 4 h within the 14-day observation period.
No deaths occurred when the rats were exposed for 15 min to concentrated vapour of the test substance.

Interpretation of results:

other: inconclusive

Remarks:

Criteria used for interpretation of results: OECD GHS

Conclusions:

In an acute inhalation study, 2/6 rats died after exposure to a vapour concentration of 8000 ppm (corresponding to 36 mg/L air) for 4 h. Thus the LC50 value was assumed to be greater than 36 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises a study which alone is regarded insufficient for assessment (Klimisch score 4). However, this study and extrapolation from the oral route including QSAR data on dermal absorption potential provide sufficient weight of evidence for hazard assessment leading to an endpoint conclusion.

Additional information

Oral

The acute toxicity via the oral route of 1,7-octadiene has been investigated in two studies.

In an acute toxic class method performed according to the OECD Guideline 423 under GLP conditions, 2 groups of 3 female rats were consecutively administered the test substance at the limit dose of 2000 mg/kg bw per gavage (2012-0086-DGT). Animals were subsequently observed for a period of 14 days. Slightly reduced motility, slight ataxia, slightly increased muscle tone, salivation, and pilo-erection were observed in all animals during the first hours after application. All findings were fully reversible within 6 hours. No animal died within the observation period. Hence, the LD50 value was determined to be > 2000 mg/kg bw. According to OECD Guideline 423, Annex 2d, a cut-off value of 5000 mg/kg bw was derived, since no mortality occurred in any step at the limit dose of 2000 mg/kg bw.

 

Furthermore, a publication on an acute oral study performed similar to the obsolete OECD Guideline 401 is available (Smyth et al., 1962 and 1969). 5 male Wistar rats per group were orally administered different doses of 1,7-octadiene via gavage. The animals were observed for a period of 14-days after test substance application. An LD50 value of 19.7 mL/kg bw is reported corresponding to 14381 mg/kg bw as calculated from a density of 0.73 g/mL. Based on limited documentation this study was considered insufficient for assessment.

In summary, the oral LD50 value of 1,7-octadiene was greater than 2000 mg/kg bw.

However, the kinematic viscosity of 1,7-octadiene (0.53 mm²/s at 40°C) indicate that the substance is likely to cause aspiration toxicity, as expected for certain hydrocarbons according to Regulation (EC) No 1272/2008. Therefore, a human health hazard related to physico-chemical properties and exposure by the oral route is identified, leading to classification for Aspiration toxicity Category 1.

 

Inhalation

In an acute inhalation toxicity study, 6 rats (sex not specified) were treated with vapours of 1,7-octadiene at a concentration of 8000 ppm, corresponding to 36 mg/L air (Smyth et al., 1962 and 1969). The rats were whole body exposed for 4 h followed by an observation period of 14 days. Two out of 6 animals died and thus an LC50 value of greater than 36 mg/L air was determined.

Additionally, 6 rats per group were exposed to air saturated with vapour of the test substance (corresponding to 129.8 mg/L based on QSAR calculation)for different time periods in order to determine the longest inhalation period which permitted all rats to survive the 14-day observation period (Smyth et al., 1962 and 1969). No mortality occurred, when rats were exposed for 15 min to a saturated atmosphere of 1,7-octadiene.

 

Dermal

One study performed similar to OECD Guideline 402 is available to evaluate the acute dermal toxicity of 1,7-octadiene (Smyth et al., 1962 and 1969). 4 male rabbits were dermally exposed to the test substance for 24 h under occlusive conditions and observed for a period of 14 days after test substance application. A LD50 value of 14.1 mL/kg bw was established, which corresponds to 10293 mg/kg bw based on a density of 0.73 g/mL. Due to the limited documentation the study is not considered sufficient for assessment.

Further information on dermal toxicity can be obtained from a reliable skin irritation study performed with 6 rabbits (82-0224-DKT). No mortality occurred and no general signs of toxicity but only slight local reaction were reported (24 h exposure, occlusive treatment).

A general prerequisite for systemic toxicity after dermal application is the permeability of the skin for the applied substance. Based on the physico-chemical parameters, a medium high dermal absorption potential was calculated and can be assigned to a dermal absorption of 40% (QSAR published by Potts and Guy, 1992; Kroes et al., 2007; Mostert and Goergens, 2011). Therefore, the dermal bioavailability is definitely lower than after oral administration (reported to be 100% for 1 mg; Danish EPA Database, 2004).

Taking into account an oral LD50 value of > 2000 mg/kg bw for rats and a dermal absorption rate of 40%, extrapolation results in a dermal LD50 value, that does not trigger a classification according to Regulation (EC) 1272/2008. This is consistent with the data from the available acute dermal toxicity data and the data from the skin irritation study.

Route-to-route extrapolation can be considered adequate for the purpose of classification and labeling and for the risk assessment of acute dermal toxicity of 1,7-octadiene. Moreover, taking into account exposure and animal welfare considerations, further testing by the dermal route is not appropriate.

Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study with the lowest dose descriptor in regard to acute oral toxicity.
Aspiration hazard is based on physico-chemical properties (kinematic viscosity) and thus not linked to a dose descriptor. Therefore, no effect level is given.

Justification for selection of acute toxicity – inhalation endpoint
There is only one study available.

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is based on a weight of evidence taking into account an available study and route-to-route extrapolation.

Justification for classification or non-classification

Oral

The available data on acute oral toxicity of 1,7-octadiene do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

However, based on a kinematic viscosity of 0.53 mm2/s, 1,7 -octadiene meets the classification criteria for Aspiration Toxicity Category 1 (H304: May be fatal if swallowed and enters airways) according to Regulation (EC) No 1272/2008.

Inhalation

The available data on acute inhalation toxicity of 1,7-octadiene do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

Dermal

Based on extrapolation from the oral route, dermal absorption potential and supported by an acute dermal toxicity study by Smyth et al. (1969) reporting an LD50 > 5000 mg/kg bw, 1,7-octadiene do not met the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.