C14-16 (even numbered) and C16 (branched) saturated and unsaturated aliphatic hydrocarbons

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

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

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:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexadec-1-ene

EC Number:

211-105-8

EC Name:

Hexadec-1-ene

Cas Number:

629-73-2

Molecular formula:

C16H32

IUPAC Name:

hexadec-1-ene

Details on test material:

This substance is very similar with regard to health endpoints to the substance being registered.
- Name of test material (as cited in study report): 1-Hexadecene
- Substance type: C16 alpha olefin
- Physical state: Liquid
- Analytical purity: 98.5%
- Impurities (identity and concentrations): 1.5% saturates
- Lot/batch No: Not reported

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: ranged from 209 to 299 grams

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposure chamber
- Source and rate of air: 2 L/min (air obtained from outside of chamber)
- System of generating particulates/aerosols: Deutrabande nebuliser within the exposure chamber and passing an air line and olefin feed line to it from outside the chamber.
- Method of particle size determination: Specifications for aerosol generator indicates that it produces particles no larger than 8 microns in diameter
TEST ATMOSPHERE
- Brief description of analytical method used: Rats exposed to very heavy mist of 1-hexadecene for 1 hour in an enclosed chamber. Visibility through the chamber (12 inches in diameter) was impossible; estimated visibility only 3 inches.
- Samples taken from breathing zone: No

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

ca. 1 h

Concentrations:

Exposure concentrations of 1-hexadecene (particles size < 8 microns) were estimated to be 8500 mg/m3.

No. of animals per sex per dose:

Not reported

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Not reported
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs and body weights were recorded.

Statistics:

No data reported.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

> 8 500 mg/m³ air

Remarks on result:

other: An LC50 value for hexadec-1-ene was not reported. However, it can be inferred from the reported results that the LC50 for hexadec-1-ene exceeds 8500 mg/m3 in male rats.

Mortality:

No mortality was observed during the study.

Clinical signs:

other: Rats exhibited a drowsy appearance and oily fur following removal from the exposure chamber.

Body weight:

The study report states that there were no significant weight changes observed during the study. Supporting raw data was not provided in the report.

Gross pathology:

The study report states that there were no significant gross pathological changes observed during necropsy. Supporting raw data was not provided in the report.

Other findings:

No data reported.

Any other information on results incl. tables

No tables included based on negative findings and absence of supporting data.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The study report does not report a LC50 value for 1-hexadecene. Drowsiness and oily fur were the only reported clinical signs of exposure. However, it can be inferred from the reported results that the LC50 for 1-hexadecene exceeds 8500 mg/m3 in male rats.

Executive summary:

Justification for Read Across

Several criteria justify the use of the read across approach to fill data gaps for Category C substances using Category A substances analogues. Category C is comprised of isomerised olefins while Category A is comprised of alpha olefins.  Studies indicate that changing the carbon number, the location of the double bond, or adding branching does not measurably alter the mammalian health endpoints. Toxicity concerns are low for alpha olefins for acute oral, dermal, and inhalation exposure. These materials are irritating to the skin of rabbits. In repeated dose oral toxicity studies, 1-hexene and 1-tetradecene have shown comparable levels of low toxicity. Female rats have exhibited alterations in body and organ weights and changes in certain hematological values at the higher doses tested and male rats have exhibited kidney damage that is most likely associated with the alpha2u-globulin protein. Screening studies indicate that 1-hexene and 1-tetradecene are not neurotoxic and do not produce adverse effects on reproduction or fetal development. Screening studies also indicate that 1-hexene, 1-octene, 1-decene, 1-dodecene, and 1 -tetradecene are not genotoxic. As a result, the weight of evidence from all of the above mammalian toxicity endpoint studies strongly suggest a low hazard potential for human health. Since the addition of branching does not measurably alter the results of studies on mammalian health endpoints, it is unlikey that there are significant toxicological differences between substances in Categories C and A.  Therefore, read across between these two categories can be justified. 

In an acute inhalation toxicity study, groups of male Wistar rats (number of animals not specified) were exposed via inhalation to 1 -hexadecene for 1 hour at an estimated aerosol mist concentration of 8500 mg/m³ (particle size less than 8.0 microns). The rats were observed for 14 days post-exposure., The rats exhibited a drowsy appearance on removal from the chamber and the fur of all animals tested was oily due to deposition of particles. No mortality, significant change in body weight or gross pathological change post autopsy was observed at the end of the 14-day observation period. Although an LC₅₀ was not reported, it can be inferred from the reported results that the LC₅₀ for 1-hexadecene exceeds 8500 mg/m3 for male rats.

This study received a Klimisch score of 2 and 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. This study will influence the DNEL(s).