Distillates (petroleum), heavy paraffinic

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

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

Adequacy of study:

supporting 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 it is an acceptable, well-documented study report following sound scientific principles.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1991

Reference 2

Reference Type:

publication

Title:

Evaluation of the acute and sub acute inhalation toxicity of lubricating oil mists

Author:

Whitman, F. T., Freeman, J. J., Infurna, R. N., Phillips, R. D.

Year:

1989

Bibliographic source:

The Toxicologist 9: 143

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Principles of method if other than guideline:

The method did not strictly follow the guideline but is deemed appropriate as utilized in this report.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Most likely 64741-88-4 and 64741-89-5

IUPAC Name:

Most likely 64741-88-4 and 64741-89-5

Constituent 2

Reference substance name:

refined, solvent-extracted paraffinic mineral base oils, sufficiently refined, IP 346 < 3%

IUPAC Name:

refined, solvent-extracted paraffinic mineral base oils, sufficiently refined, IP 346 < 3%

Test material form:

other: Oily liquids

Details on test material:

Since PAC are not likely to cause any adverse local effects in lungs after sub-actute exposure, the sufficiently refined lubricant base oils can be used as read-across for this endpoint.


Test Substance: Two refined, solvent-extracted paraffinic mineral base oils The oils spanned a range of 60 - 150 SUS @ 100°F, approximately 12-30 mm2/s).

- Substance Type: Other Lubricant Base Oils (Sufficiently Refined, IP 346 < 3%)

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Duration of treatment / exposure:

2 weeks

Frequency of treatment:

6 hours/day

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 500, and 1500 mg/m3
Basis:

Control animals:

other: no data

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Effect levels

1

Dose descriptor:

NOAEC

Remarks:

For pulmonary toxicity

Effect level:

ca. 500 mg/m³ air

Sex:

not specified

Basis for effect level:

other: Pulmonary toxicity including focal infiltrations of inflammatory cells, focal hyperplasia and squamous metaplasia of the nasal mucosa, and accumulations of inflammatory exudates in the lumen of the nasal cavity

2

Dose descriptor:

NOAEC

Remarks:

For systemic toxicity

Effect level:

>= 1 500 mg/m³ air

Sex:

not specified

Basis for effect level:

other: Based on the lack of systemic toxicity observed at this dose level.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

There were no mortalities.  Exposure-related changes were noted in  animals from the most highly exposed groups.  These changes, including  focal infiltrations of inflammatory cells, focal hyperplasia and squamous  metaplasia of the nasal mucosa, and accumulations of inflammatory  exudates in the lumen of the nasal cavity, were interpreted as the result  of a mild irritating process in the nasal mucosa.  No other microscopic  changes were observed in any other tissues that indicated systemic  toxicity from exposure to the refined lubricant base oils.  The NOAEL for  pulmonary effects was 500 mg/m3, and the NOAEL for systemic effects was  >1500 mg/m3.

Applicant's summary and conclusion

Conclusions:

The NOAEC for pulmonary effects was 500 mg/m3, and the NOAEC for systemic effects was ≥1500 mg/m3.

Executive summary:

Justification for Read Across

Since PAC are not likely to cause any adverse local effects in lungs after sub-actute exposure, sufficiently well-refined lubricant base oils can be sued as read-across for this endpoint.

Two solvent-extracted paraffinic mineral base oils were evaluated in 2-week inhalation toxicity studies (Whitmanet al., 1989; EBSI, 1991 a,b).The oils spanned a range of 60 – 150 SUS @ 40^oC, approximately 12-30 mm²/s). Rats were exposed 6 hours/day to aerosol concentrations of approximately 0, 50, 500, and 1500 mg/m³. There were no mortalities but exposure-related changes were noted in animals from the most highly exposed groups. These changes, including focal infiltrations of inflammatory cells, focal hyperplasia and squamous metaplasia of the nasal mucosa, and accumulations of inflammatory exudates in the lumen of the nasal cavity, were interpreted as the result of a mild irritating process in the nasal mucosa. No other microscopic changes were observed in any other tissues that indicated systemic toxicity from exposure to the lubricant base oils. The NOAEC for pulmonary effects was 500 mg/m³, and the NOAEC for systemic effects resulting from inhalation exposure was ≥1500 mg/m³. 

This study is classified as reliable with restrictions because it is an acceptable, well-documented study report following sound scientific principles.