Icos-1-ene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable with restrictions because although the study was not GLP compliant, it appears that the study methods used are similar to OECD guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1967

Report date:

1967

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Study was performed prior to adoption of the test guideline specified.

GLP compliance:

no

Test type:

other: Screening and standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hex-1-ene

EC Number:

209-753-1

EC Name:

Hex-1-ene

Cas Number:

592-41-6

IUPAC Name:

hex-1-ene

Details on test material:

This substance is very similar in structure to the substance being registered.

- Name of test material (as cited in study report): 1-Hexene
- Substance type: C6 alpha olefin
- Physical state: liquid
- Analytical purity: 98.5%
- Impurities (identity and concentrations): 1.5% saturates

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: vapour inhalation screening (between 203 and 239 grams); acute vapour 4 hour LC50 (between 200 and 290 grams)

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass cylinder chamber
- Exposure chamber volume: Approximately 20 litres
- Source and rate of air: Vapour inhalation screening (2 L/min; source not reported); acute vapour 4 hour LC50 (not reported)
- System of generating particulates/aerosols: Vapour inhalation screening (air was passed through a large bubbler containing 1-hexene and the saturated vapours directed to the chamber (method not detailed)); acute vapour 4 hour LC50 (doses were established by preparing vapours and diluting with air to the desired concentration)
- Brief description of analytical method used: Vapour inhalation screening (theoretical chamber concentrations were calculated on the basis of bubbler weight loss and amount of air passed through the bubbler); acute vapour 4 hour LC50 (M.S.A combustible gas indicator calibrated for 1-hexene was used to measure concentration of 1-hexene from exposure chamber during study).
- Samples taken from breathing zone: Vapour inhalation screening: no; acute vapour 4 hour LC50 : yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

acute vapour 4 hour LC50

Duration of exposure:

ca. 4 h

Concentrations:

161,000 parts per million (acute vapour inhalation screening)
0, 27,600; 28,600; 30,500; 33,200; 37,000; and 41,200 parts per million (acute vapour 4 hour LC50)

No. of animals per sex per dose:

10

Control animals:

other: acute vapour inhalation screening:no; acute vapour 4 hour LC50: yes

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs and body weight were noted during study.

Statistics:

Estimated by plotting the percentage mortality versus chamber concentration and applying the Litchfield method to obtain the LC50.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

32 000 ppm

95% CL:

30 000 - 34 200

Remarks on result:

other: Equivalent to 110,148 mg/m3 or 110.1 mg/L

Mortality:

Mortality was observed in all groups except the lowest dose group (27,600 parts per million) with mortality rates increasing with increasing concentration. Reported mortality rates were: 28,600 (2/10); 30,500 (5/10); 33,200 (7/10); 37,000 (8/10); and 41,200 (10/10) parts per million. No mortalities were observed at the control (0 ppm) and lowest dose level (27,600 ppm).

Clinical signs:

other: Signs of light anaesthesia appeared at the lowest exposure concentration and increased markedly at higher concentrations of 1-hexene. Some animals became prostrate and exhibited slow breathing prior to death. Animals that survived the exposure period, rec

Body weight:

Supporting raw data for body weights was not provided in the study report. Tabulated body weight changes were reported as percent weight change in tabular form for days 1, 2, 3,4, 7, and 14. It is unclear how the weight changes were calculated and the significance of the values reported is unknown since the study report does not discuss weight change results.

Gross pathology:

No gross pathological findings were noted in any rat during necropsy.

Other findings:

No data reported.

Any other information on results incl. tables

Table 1: Study results for acute vapour 4 hour LC50 for 1-hexene in the rat
1-hexene concentration (parts per million)	Number of male rats	Mortality	Time range of death (minutes)
0	10	0	N/A
27,600	10	0	> 240
28,600	10	2	120 to 240
30,500	10	5	90 to 240
33,200	10	7	60 to 240
37,000	10	8	60 to 235
41,2000	10	10	40 to 235

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Not classified because LC50 is greater than the requirements for a Category 4 vapour toxicant (20 mg/L) Criteria used for interpretation of results: EU

Conclusions:

The LC50 of 1-hexene in male rats was estimated to be 32,000 parts per million.

Executive summary:

In an acute vapour inhalation screening study, 10 male Wistar rats were exposed to saturated vapours of 1-hexene. Signs of toxicity included rapid anaesthesia, excitement within 1 minute, tremors within 2 minutes, convulsions within 3 minutes, and death for all animals within 5 minutes. The chamber concentration was estimated to be 161,000 parts per million 1-hexene (16.1% by volume).

In an acute inhalation toxicity study, groups of adult Wistar male rats (10/dose) were exposed by inhalation route to 1-hexene for 4 hours (whole body exposure) at concentrations of 0, 27,600; 28,600; 30,500; 33,200; 37,000; and 41,200 parts per million. Animals were then observed for 14 days. Mortality was observed in all groups except the lowest dose group (27,600 parts per million) with mortality rates increasing with increasing concentration. Reported mortality rates were: 28,600 (2/10); 30,500 (5/10); 33,200 (7/10); 37,000 (8/10); and 41,200 (10/10) parts per million. The LC50 of 1-hexene was estimated to be 32,000 parts per million. Signs of light anaesthesia appeared at the lowest exposure concentration and increased markedly at higher concentrations of 1-hexene. Some animals became prostrate and exhibited slow breathing prior to death. Animals that survived the exposure period, recovered soon after removal from the chamber and survived through day 14 of the observation period. Autopsies of animals that died during exposure and those that survived till 14 days post-exposure did not reveal any significant gross pathological changes.

This study received a Klimisch score of 2 and is classified as reliable with restrictions because although the study is not GLP compliant, it appears that the study methods used are similar to OECD guidelines.