Mono-, and di-(sec-hexadecyl)naphthalene

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:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The documentation is from secondary literature with limited detail

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Unnamed

Year:

2004

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1978

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Federal Hazardous Substances Act (FHSA), CFR Title 21

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

1 hour exposure duration

GLP compliance:

no

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Diisononylnaphthalene

EC Number:

264-290-2

EC Name:

Diisononylnaphthalene

Cas Number:

63512-64-1

Molecular formula:

C28H44

IUPAC Name:

2,7-bis(7-methyloctyl)naphthalene

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The rats received a single exposure to the aerosolized test substance in an inhalation chamber. The duration of the exposure was 1 hour. The spray was introduced into the chamber via a nebulizer and directed away from the animals. The chamber was saturated with 17 mg/L of the test material.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

ca. 1 h

Concentrations:

17 mg/L

No. of animals per sex per dose:

5/sex/dose (total of 10 animals)

Control animals:

not specified

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 17 mg/L air

Exp. duration:

1 h

Applicant's summary and conclusion

Interpretation of results:

other: data to be used for supporting purposes only

Remarks:

Criteria used for interpretation of results: other: insufficient study detail

Conclusions:

The LC50 for acute inhalation exposure to aerosolized diisononylnaphthalene is greater than 17 mg/L for male and female rats. This study adds to the weight of evidence supporting the low potential for acute toxicity via the inhalation route of exposure for the study substance. Diisononylnaphthalene is deemed appropriate for read-across for the study substance based on similar functionality and metabolism. The extent of enzymatic oxidative attack at the aromatic ring structure of naphthalene (i.e. ring expoxidation) is a key step in mediating its subsequent toxicity. Available data demonstrate that extensive oxidation of the aromatic nucleus of naphthalene and shorter-chain length alkylated naphthalenes (e.g. monomethyl derivatives) does not occur with alkylated naphthalene derivatives with a carbon chain-length of four or greater where the major metabolites involve side-chain oxidation and do not include reactive harmful intermediates (i.e. aromatic epoxides). Experimental as well as modeling data indicate that this trend is expected to continue as alkyl chain length increases. In addition, it is known in general that certain physical properties vary in a predictable manner as alkyl chain length increases, making a compound less favorable for absorption as carbon number increases. All read-across data are for test materials with alkyl carbon number greater than 3, but less than the study substance (alkyl carbon chain length of 16). Therefore, the toxicity exhibited by these data would be a worst case estimate of the likely toxicity of the study substance.

Executive summary:

Aerosolized diisononylnaphthalene was administered in an inhalation chamber to ten Wistar rats to assess acute inhalation toxicity. The duration of the exposure was 1 hour. The spray was introduced into the chamber via a nebulizer and directed away from the animals. The chamber was saturated with 17 mg/L of the test material. The acute median lethal concentration (LC50) for the test material was >17 mg/L for male and female rats evaluated in the study. There were no signs of clinical effects or gross toxicity.

Diisononylnaphthalene is a di-substituted alkylated naphthalene deemed to be appropriate for read-across for the study substance based on similar functionality and metabolism. The extent of enzymatic oxidative attack at the aromatic ring structure of naphthalene (i.e. ring expoxidation) is a key step in mediating its subsequent toxicity. Available data demonstrate that extensive oxidation of the aromatic nucleus of naphthalene and shorter-chain length alkylated naphthalenes (e.g. monomethyl derivatives) does not occur with alkylated naphthalene derivatives with a carbon chain-length of three or greater (Lin CY et al. 2009). Therefore the metabolic profiles of both diisononylnaphthalene and the study substance do not include generation of toxic metabolites. In addition, these two substances can be considered to be members of a homologous series of branched alkyl naphthalenes. It is known in general that certain physical properties vary in a predictable manner as one ascends a given homologous series (i.e. increasing alkyl chain length), and that the differences between adjacent homologues decreases as overall chain length increases. Considering neither the study substance nor diisononylnaphthalene undergo bioactivation (i.e. ring epoxidation), any differences in toxicological properties of these two substances would therefore be governed by their absorption, which, in turn would be expected to be dictated by any differences in their physical-chemical properties, arising from their molecular weights. Based on the close proximity of the average molecular weights of diisononylnaphthalene (380.7 g/mol, King Industries, 2004) and the primary component of the study substance (352.6 g/mol), any toxicity, or lack there-of, exhibited by the read-across substance is adequately predictive of the toxicity of the study substance.