Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to guideline standards in context of the National Toxicology Program with detailed decription
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Remarks:
Batelle Toxicology Northwest (Richland, WA)
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Cumene
EC Number:
202-704-5
EC Name:
Cumene
Cas Number:
98-82-8
Molecular formula:
C9H12
IUPAC Name:
isopropylbenzene
Details on test material:
- Name of test material (as cited in study report): Cumene

- Substance type:
- Physical state: colorless liquid with a sharp, penetrating, aromatic odour
- Analytical purity: 99.9% peak area
- Impurities (identity and concentrations): No impurities >0.05% peak area detected
- Purity test date: Not specified
- Lot/batch No.: Lot 200556852
- Expiration date of the lot/batch: No data
- Stability under test conditions: stable over the test period, no degradation of bulk chemical was detected

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Taconic Laboratory Animals and Services (Germantown, NY)
- Age at study initiation: approx. 6 weeks old on first day of study
- Weight at study initiation: 19.0+/-0.2 to 23.4 +/- 0.3 g
- Fasting period before study:
- Housing: individually
- Diet (e.g. ad libitum): NTP-2000 irradiated pelleted diet (Zeigler Brothers, Inc, Gardeners, PA); changed weekly
- Water (e.g. ad libitum): Tap water (Richland, WA, muncipal supply) via automatic watering system (Edstrom Industries, Waterford, WI)
- Acclimation period: 11 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 +/- 2 (75 +/- 2° F)
- Humidity (%): 55 +/- 15
- Air changes (per hr): 15 +/- 2
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: gas
Vehicle:
- Vehicle(s)/solvent(s) used: unchanged (no vehicle)
Duration of treatment / exposure:
6 h plus T90 (=12 min)
Frequency of treatment:
5 days per week (excluding holidays) for 14 weeks
Post exposure period:
none
Doses / concentrations
Remarks:
Doses / Concentrations:
62.5, 125, 250, 500, and 1000 ppm
Basis:
nominal conc.
No. of animals per sex per dose:
9-10
Control animals:
yes, concurrent vehicle
Positive control(s):
none

Examinations

Tissues and cell types examined:
blood smears from peripherial blood.
Details of tissue and slide preparation:
Smears were immediately prepared and fixed in absolute methanol.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not examined
Additional information on results:
No increase in micronucleated erythrocytes was observed in peripheral blood of male or female mice exposed to cumene by inhalation (62.5 to 1,000 ppm) for 3 months. For both male and female mice, no significant changes in the percentage of PCEs were observed over the exposure range tested, indicating an absence of treatment-related toxicity to the bone marrow.

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): see table below
- Ratio of PCE/NCE (for Micronucleus assay): see table below
- Statistical evaluation: see table below

Any other information on results incl. tables

Frequency of Micronuclei in Peripheral Blood Erythrocytes of Mice Following Treatment with Cumene by Inhalation for 3 Months[a]

Compound

Dose (ppm)

Number of male rats with erythrocytes scored

Micronucleated PCEs/ 1000 PCEs [b]

Pairwise P value [c]

PCE [b] (%)

Male

Air [d]

0

10

2.40 ± 0.69

2.7 ± 0.1

Cumene

62.5

10

2.20 ± 0.66

0.6161

2.6 ± 0.1

125

10

2.10 ± 0.48

0.6728

2.6 ± 0.1

250

10

1.80 ± 0.36

0.8230

2.8 ± 0.1

500

10

2.00 ± 0.26

0.7270

2.9 ± 0.1

1,000

10

2.20 ± 0.42

0.6161

2.9 ± 0.2

P=0.553 [e]

Female

Air

0

10

2.30 ± 0.40

3.3 ± 0.1

Cumene

62.5

9

1.33 ± 0.37

0.9396

2.3 ± 0.1

125

10

1.70 ± 0.30

0.8289

3.1 ± 0.2

250

10

2.10 ± 0.53

0.6186

3.3 ± 0.2

500

10

2.10 ± 0.35

0.6186

3.4 ± 0.1

P=0.329

[a] Study was performed at ILS, Inc. The detailed protocol is presented by MacGregor et al. (1990).

NCE=normochromatic erythrocyte; PCE=polychromatic erythrocyte

[b] Mean ± standard error

[c] Pairwise comparison with the chamber controls, significant at P#0.025 (PCEs) or P#0.005 (NCEs) (ILS, 1990)

[d] Chamber control

[e] Significance of micronucleated NCEs/1,000 NCEs tested by the one-tailed trend test, significant at P#0.025 (ILS, 1990)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
No increase in micronucleated erythrocytes was observed in peripheral blood of male or female mice exposed to cumene by inhalation for 3 months.
Executive summary:
No increase in micronucleated erythrocytes was observed in peripheral blood of male or female mice exposed to cumene by inhalation (62.5 to 1,000 ppm) for 3 months. For both male and female mice, no significant changes in the percentage of PCEs were observed over the exposure range tested, indicating an absence of treatment-related toxicity to the bone marrow.