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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:

Justification for Read Across

Several criteria justify the use of the read across approach to fill data gaps fo risomerised olefins; alpha, internal, linear and branched – multiple carbon numbersubstances using linear alpha olefin substances. Studies indicate that changing the carbon number, the location of the double bond, or adding branching does not measurably alter effects on mammalian health endpoints. There is a consistent toxicity potency pattern for linear alpha olefins supported by a low toxicity concern for acute oral, dermal and inhalation exposure. These materials are slightly irritating to skin and slightly to non-irritating to eyes of rabbits. In repeat dose toxicity studies, hex-1-ene and tetradec-1-ene have shown comparable levels of low toxicity, with female rats exhibiting alterations in body and organ weights and changes in certain haematological values at the higher doses tested; male rats exhibiting nephropathy presumed to be associated with the alpha2u-globulin protein. Screening studies indicate that they are not neurotoxic (for hex-1-ene and tetradec-1-ene), do not produce adverse effects on reproduction or foetal development (hex-1-ene and tetradec-1-ene), and are not genotoxic (hex-1-ene, oct-1-ene, dec-1-ene, dodec-1-ene, and tetradec-1-ene). Study results for the aforementioned endpoints indicate a low hazard potential for human health. Since the addition of branching does not measurably alter the results of studies on mammalian health endpoints, there should not be any toxicological differences between substances in multiple carbon number isomerised olefins and linear alpha olefins.  Therefore, read across between these two categories can be justified.

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.