Hydrocarbons, C10, aromatics, <1% naphthalene

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented publication which meets basic scientific principles.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented publication which meets basic scientific principles.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

reduced body weight gain in 1500 ppm group

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Chromosome Aberrations in Sprague-Dawley Rats

Post-Exposure Interval	Exposure Group	Number	Number of Spreads	Number of Aberrations	% Abrr. Per Metaphase	% Metaphases > 1 Abrr.	% Metaphases > 2 Abrr.
6-hours	Air	8	400	0	0	0	0
	150 ppm	9	450	0	0	0	0
	500 ppm	10	487	0	0	0	0
	1500 ppm	9	450	0	0	0	0
24 hours	Air	9	450	1	0.2	0.2	0
	150 ppm	10	482	0	0	0	0
	500 ppm	10	500	0	0	0	0
	1500 ppm	10	500	1	0.2	0.2	0
	Cyclo-phosphamide	9	453	130	28.7	14.6	8.2
48 hours	Air	4	200	0	0	0	0
	150 ppm	4	200	0	0	0	0
	500 ppm	4	200	0	0	0	0
	1500 ppm	3	150	0	0	0	0

Conclusions:

Interpretation of results: negative
The test substance was not clastogenic at levels up to and including 1500 ppm.

Executive summary:

This data is being read across from the source study that tested Hydrocarbons, C9 aromatics based on analogue read across.

A rat bone marrow cytogenicity study was performed to determine the clastogenicity of high flash aromatic naphtha. 15 male and 15 female rats were exposed via inhalation to 150, 500, or 1500 ppm of high flash aromatic naphtha for 6 hrs/day for 5 days. Rats were sacrificed at 6, 24, or 48 hrs after end of exposure, and the bone marrow then examined for chromosome and chromatid aberrations. There was no increase in the number of aberrations as compared to negative controls in any of the exposure groups. A significant increase in the number of aberrations was seen in the positive control group, therefore the test is valid. In conclusion, the test substance is not clastogenic.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

GLP compliance:

yes

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Hydrocarbons, C9, aromatics

EC Number:

918-668-5

Molecular formula:

None available - not a single isomer - see remarks.

IUPAC Name:

Hydrocarbons, C9, aromatics

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Details on exposure:

- Exposure apparatus: 16 m glass and steel chambers.
- Method of holding animals in test chamber: cages
- Source and rate of air: Air was provided by a separate HVAC system.
- Method of conditioning air: Air was filtered for particulates and temperature and humidity controlled.
- System of generating particulates/aerosols: Test atmosphere was generated by heating nitrogen to 200°C by passing it through a 1 L stainless steel cylinder with a 1500 W band heater. The nitrogen then passed through a glass column 7.6 cm diameter and 30 cm long packed with glass beads. Test material was delivered by a metering pump into Teflon tubing, to the bottom of the column. The liquid test substance vaporized as it went up the column with the nitrogen. The vapor then went into the test chambers where dilution with the chamber ventilation air produced the desired concentrations.- Temperature, humidity, pressure in air chamber: Air flow rate, temperature and relative humidity were monitored every half-hour during exposure.

TEST ATMOSPHERE
- Brief description of analytical method used: Measurements made hourly using gas-phase IR.
- Samples taken from breathing zone: yes

Duration of treatment / exposure:

6 hours/day

Frequency of treatment:

5 days

Post exposure period:

6, 24, or 48 hours

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
150 ppm
Basis:
nominal conc.
153 (9.6) ppm measured

Doses / concentrations 2

Remarks:

Doses / Concentrations:
500 ppm
Basis:
nominal conc.
471 (13.1) ppm measured concentration

Doses / concentrations 3

Remarks:

Doses / Concentrations:
1500 ppm
Basis:
nominal conc.
1540 (48) ppm measured concentration

No. of animals per sex per dose:

15 male/15 female

Control animals:

yes, concurrent no treatment

Positive control(s):

10 animals of each sex were exposed to cyclophosphamide
- Route of administration: injected intraperitoneally
- Doses / concentrations: 40 mg/kg

Examinations

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION: 4 slides per rat were stained with Giemsa.


METHOD OF ANALYSIS: Slides were scanned for well resolved metaphase spreads. Fifty metaphases per animal were evaluated.

Evaluation criteria:

total number of chromosome aberrations, frequency of aberrations per metaphase, percent metaphases with one or more aberrations, percent metaphases with two or more aberrations

Statistics:

Kruskal-Wallis multiple group comparison test followed by the Mann-Whitney U test

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

reduced body weight gain in 1500 ppm group

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Chromosome Aberrations in Sprague-Dawley Rats

Post-Exposure Interval	Exposure Group	Number	Number of Spreads	Number of Aberrations	% Abrr. Per Metaphase	% Metaphases > 1 Abrr.	% Metaphases > 2 Abrr.
6-hours	Air	8	400	0	0	0	0
	150 ppm	9	450	0	0	0	0
	500 ppm	10	487	0	0	0	0
	1500 ppm	9	450	0	0	0	0
24 hours	Air	9	450	1	0.2	0.2	0
	150 ppm	10	482	0	0	0	0
	500 ppm	10	500	0	0	0	0
	1500 ppm	10	500	1	0.2	0.2	0
	Cyclo-phosphamide	9	453	130	28.7	14.6	8.2
48 hours	Air	4	200	0	0	0	0
	150 ppm	4	200	0	0	0	0
	500 ppm	4	200	0	0	0	0
	1500 ppm	3	150	0	0	0	0

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative
The test substance was not clastogenic at levels up to and including 1500 ppm.

Executive summary:

A rat bone marrow cytogenicity study was performed to determine the clastogenicity of high flash aromatic naphtha. 15 male and 15 female rats were exposed via inhalation to 150, 500, or 1500 ppm of high flash aromatic naphtha for 6 hrs/day for 5 days. Rats were sacrificed at 6, 24, or 48 hrs after end of exposure, and the bone marrow then examined for chromosome and chromatid aberrations. There was no increase in the number of aberrations as compared to negative controls in any of the exposure groups. A significant increase in the number of aberrations was seen in the positive control group, therefore the test is valid. In conclusion, the test substance is not clastogenic.