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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

There are conclusive but not sufficient data for the classification of substance Stoddard solvent with regard to mutagenicity/genetic toxicity. It is concluded that the substance Stoddard solvent does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity

In vitro summary: Mutagenicity testing results for Stoddard solvent  has been reported in several studies using bacterial and mammalian cells. There was no indication of genotoxicity in any of the studies.

In vivo summary: Mutagenicity testing showed no evidence of genotoxicity.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
Stoddard solvent; boiling range, 157-204°C; 19% aromatics
Target gene:
histidine
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
With and without Aroclor induced rat liver S9
Test concentrations with justification for top dose:
0.001-5 µg/plate and 3.38-25 µl/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: not stated
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 1103
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation)

DURATION
- Preincubation period: not applicable
- Exposure duration: 48 hours

NUMBER OF REPLICATES: duplicate test, each performed with triplicate plates

DETERMINATION OF CYTOTOXICITY
- Method: growth of bacterial lawn
Evaluation criteria:
For a substance to be considered positive, it should have induced a concentration-related and statistically significant increase in mutation rate in one or more starins of bacteria in the presence and/or absence of S9 in both experiments at sub-toxic concentrations. To be considered negative the number of induced revertants compared to spontaneous revertants should be less than two-fold at each concentration employed.
Statistics:
Methods recommended by the United Kingdom Environmental Mutagen Society and normally Dunnett's method of linear regression
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: no data

COMPARISON WITH HISTORICAL CONTROL DATA: vehicle control results said to be "within the normal range"

ADDITIONAL INFORMATION ON CYTOTOXICITY: no further data
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

 

 

 

Conclusions:
Interpretation of results :negative
In a reliable study, performed according to OECD guideline 471, the Stoddard solvent did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at dose levels of 0.001-5 µg/plate and 3.38-25 µl/ml . This concentration was not cytotoxic.
Executive summary:

Interpretation of results :negative

In a reliable study, performed according to OECD guideline 471, the Stoddard solvent did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at dose levels of 0.001-5 µg/plate and 3.38-25 µl/ml . This concentration was not cytotoxic.

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
Stoddard solvent; 15% aromatics

Target gene:
histidine
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
With and without Aroclor induced rat liver S9
Test concentrations with justification for top dose:
0.001-5 µg/plate and 3.38-25 µl/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: not stated
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 1103
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation)

DURATION
- Preincubation period: not applicable
- Exposure duration: 48 hours

NUMBER OF REPLICATES: duplicate test, each performed with triplicate plates

DETERMINATION OF CYTOTOXICITY
- Method: growth of bacterial lawn
Evaluation criteria:
For a substance to be considered positive, it should have induced a concentration-related and statistically significant increase in mutation rate in one or more starins of bacteria in the presence and/or absence of S9 in both experiments at sub-toxic concentrations. To be considered negative the number of induced revertants compared to spontaneous revertants should be less than two-fold at each concentration employed.
Statistics:
Methods recommended by the United Kingdom Environmental Mutagen Society and normally Dunnett's method of linear regression
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: no data

COMPARISON WITH HISTORICAL CONTROL DATA: vehicle control results said to be "within the normal range"

ADDITIONAL INFORMATION ON CYTOTOXICITY: no further data
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

 

 

 

Conclusions:
Interpretation of results :negative
In a reliable study, performed according to OECD guideline 471, the Stoddard solvent did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at dose levels of 0.001-5 µg/plate and 3.38-25 µl/ml . This concentration was not cytotoxic.
Executive summary:

Interpretation of results :negative

In a reliable study, performed according to OECD guideline 471, the Stoddard solvent did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at dose levels of 0.001-5 µg/plate and 3.38-25 µl/ml . This concentration was not cytotoxic.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
Principles of method if other than guideline:
Well-conducted study according to protocol very similar to OECD guideline 473
GLP compliance:
not specified
Type of assay:
in vitro mammalian cell micronucleus test
Target gene:
not applicable
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
- Type and identity of media: minimum essential medium
- Properly maintained: no data
- Periodically checked for Mycoplasma contamination: no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
liver microsomal fraction from male rats prepared according to Ames et al., 1977
Test concentrations with justification for top dose:
Doses:
0, 0.007, 0.013, 0.025, 0.05 uL/mL (without activation)
0, 0.05, 0.1, 0.2, 0.4 uL/mL (with activation)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: solubility
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
without metabolic activation
Positive control substance:
ethylmethanesulphonate
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
with metabolic activation
Positive control substance:
cyclohexylamine
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: not applicable
- Exposure duration: 4 hours
- Expression time (cells in growth medium): not applicable
- Selection time (if incubation with a selection agent): not applicable
- Fixation time (start of exposure up to fixation or harvest of cells): 7 and 24 (or 28) hours @ 20 ug/ml, 18 hours @ 0.6, 10 and 20 ug/ml

SPINDLE INHIBITOR (cytogenetic assays): colcemia, 0.2 ug/ml

STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: 2 cultures per concentration

NUMBER OF CELLS EVALUATED: 100 per slide, 200 per concentration

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

OTHER EXAMINATIONS:
- Determination of polyploidy: no data
- Determination of endoreplication: no data
Evaluation criteria:
To be considered positive, either a statistically significant, concentration-related increase in the number of structural chromosome aberrations, or a statistically signficant positive response at one of the concentrations
Statistics:
Chi-squared test performed for cells with aberration (excluding gaps)
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: insoluble
- Precipitation: no data
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES: yes, but no data presented

COMPARISON WITH HISTORICAL CONTROL DATA: no data

Remarks on result:
other: negative for Chinese hamster Ovary (CHO)(all strains/cell types tested);
Conclusions:
Interpretation of results:negative
In a reliable study, according to a protocol that is similar to OECD 473, Stoddard solvent did not increase the incidence of chromosome aberrations in Chinese hamster Ovary (CHO) cells in the presence or absence of metabolising fraction at concentrations up to 0.4 ug/ml. There was no evidence of cytotoxicity at this dose level.

Executive summary:

Interpretation of results:negative

In a reliable study, according to a protocol that is similar to OECD 473, Stoddard solvent did not increase the incidence of chromosome aberrations in Chinese hamster Ovary (CHO) cells in the presence or absence of metabolising fraction at concentrations up to 0.4 ug/ml. There was no evidence of cytotoxicity at this dose level.

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction:QSAR method for chemicals properties assessment. Relevant for in vitro (Ames test) mutagenicity endpoints.
Qualifier:
according to guideline
Guideline:
other: ToxTree: Benigni/Bossa rules for carcinogenicity and mutagenicity
Principles of method if other than guideline:
This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs). The SAs for mutagenicity are molecular functional groups or substructures known to be linked to the mutagenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential mutagenicity of the chemical. The present list of SAs is a subset of the original Toxtree list, obtained by eliminating the SAs for nongenotoxic carcinogenicity.
GLP compliance:
no
Remarks:
not applicable. QSAR model in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs) relevant for in vitro (Ames test) mutagenicity endpoints.
Type of assay:
other: QSAR model
Target gene:
This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs).
Species / strain / cell type:
S. typhimurium TA 100
Test concentrations with justification for top dose:
QSAR model in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs) relevant for in vitro (Ames test) mutagenicity endpoints.
Untreated negative controls:
other: QSAR model
Negative solvent / vehicle controls:
other: QSAR model
True negative controls:
other: QSAR model
Positive controls:
other: QSAR model
Details on test system and experimental conditions:
This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree.
Evaluation criteria:
This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs). The SAs for mutagenicity are molecular functional groups or substructures known to be linked to the mutagenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential mutagenicity of the chemical. The present list of SAs is a subset of the original Toxtree list, obtained by eliminating the SAs for nongenotoxic carcinogenicity.
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
other: QSAR model
Untreated negative controls validity:
other: QSAR model
Additional information on results:
Benigni/Bossa rules for carcinogenicity and mutagenicity:
- Structural Alert for genotoxic carcinogenicity NO
- Potential S. typhiunium TA100 mutagen based on QSAR NO
- Negative for genotoxic carcinogenicity YES

1.6. Profiling results:

DNA binding by OECD

No alert found

Est rogen Receptor Binding

Non binder, non cyclic structure

OECD HPV Chemical Categories

C9-13 Aliphatics hydrocarbon solvents (less than 2 percent aromatics)

Protein binding by OECD

No alert found

Protein binding potency

Not possible to classify according to these rules (GSH)

Superfragments

No superfragment

Toxic hazard classification by Cramer (original)

Low (Class I)

US-EPA New Chemical Categories

Not categorized.

Conclusions:
Interpretation of results ):negative
No alert found.The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS.
The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS and therefore Stoddard solvent does not cause in vitro mutagenicity (Ames test)
Executive summary:

The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS and does not cause in vitro mutagenicity (Ames test).

No mutagenic activity in the (Q)SAR study, In vitro mutagenicity (Ames test) alerts by ISS for  Stoddard solvent and does not cause in vitro mutagenicity (Ames test) .This QSAR method is Relevant for in vitro (Ames test) mutagenicity endpoints.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

There are conclusive but not sufficient data for the classification of substance Stoddard solvent with regard to mutagenicity/genetic toxicity. It is concluded that the substance Stoddard solvent does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity

In vitro summary: Mutagenicity testing results for Stoddard solvent  has been reported in several studies using bacterial and mammalian cells. There was no indication of genotoxicity in any of the studies.

In vivo summary: Mutagenicity testing showed no evidence of genotoxicity.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
no
GLP compliance:
not specified
Type of assay:
micronucleus assay
Specific details on test material used for the study:
White Spirits containing 15% aromatics with an initial boiling point of 160°C to 161°C
Species:
mouse
Strain:
Balb/c
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:mouse (Balb/c) male/female
- Age at study initiation: 7-8 weeks
- Weight at study initiation: males 21-27 g, females 21-26 g
- Assigned to test groups randomly: yes, under following basis: allocated to treatment groups according to randomization table generated by computer programme or manually
- Fasting period before study: yes, overnight until 3-4 hours after dosing
- Housing: males, 1/cage, macrolon cages type I; females, <=3/cage, macrolon cages type II; filled with clean softwood bedding
- Diet (e.g. ad libitum): standard animal diet, Altromin No. 1314, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: >=6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25 +- 3 (occasionally 20-25)
- Humidity (%): 40 - 50 (occasionally 45-70)
- Air changes (per hr): no data, except "air-conditioned room"
- Photoperiod (hrs dark / hrs light): 12 / 12

I
Route of administration:
intraperitoneal
Details on exposure:
Intraperitoneal injections of 0.1, 0.05 and 0.01 ml of white spirit (initial boiling point, 160°C; 15% aromatics) were given to 10 animals each, while inhalation of 50 g/m3 for 5 lots of 5 min (each exposure period was separated by 5 min without exposure) was performed with five mice.
Duration of treatment / exposure:
single administration
Frequency of treatment:
single administration
Post exposure period:
2-4 hours post exposure , animals were sacrificed
Remarks:
Doses / Concentrations:0.1, 0.05 and 0.01 ml
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Justification for choice of positive control(s): not stated
Tissues and cell types examined:
bone marrow
Statistics:
Method used: Kastenbaum & Bowman
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
no cytogenic damage in a micronucleus test conducted with BALB/c mice.
Conclusions:
Interpretation of results : negative
no cytogenic damage in a micronucleus test conducted with BALB/c mice.
Genotoxicity: negative (male/female); toxicity: no effects
Mutagenicity testing of Stoddard solvent showed no evidence of genotoxicity.
Executive summary:

Mutagenicity testing of Stoddard solvent showed no evidence of genotoxicity.

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
no
GLP compliance:
not specified
Type of assay:
micronucleus assay
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc.
- Age at study initiation:
- Weight at study initiation:
- Assigned to test groups randomly: yes
- Fasting period before study:
- Housing: up to 4 rats per cage.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: none
Details on exposure:
Three groups of 15 male and 15 female rats were given a single i.p. dose of either 0.3, 1 or 3 g
Duration of treatment / exposure:
6 to 48 hours
Frequency of treatment:
single i.p. dose
Remarks:
Doses / Concentrations:
0, 0.3 g/kg, 1.0 g/kg, 3.0 g/kg
No. of animals per sex per dose:
Three groups of 15 male and 15 female rats
Control animals:
yes, concurrent vehicle
Positive control(s):
triethylenemelamine

- Route of administration: i.p
- Doses / concentrations: single dose/ 0.8 mg/kg
Tissues and cell types examined:
bone marrow
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION:
After centrifugation was repeated and cells were left overnight, the fixative cells were dropped onto glass slides and air dried. Spreads were stained with 5% Giemsa at pH 6.8. After drying, slides were coverslipped.

METHOD OF ANALYSIS:
slides were coded and scored for chromosomal aberrations.
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Interpretation of results : negative
In a rat bone marrow micronucleus assay 15 males were treated via intraperitonea with Stoddard solvent at doses of
0.3, 1 and 3 g/kg. Bone marrow cells were harvested 24 hours after 48 hour treatment.
There were no signs of toxicity during the study. The positive control induced the appropriate response.
There was not a significant increase in the frequency of micronucleated polychromatic erythocytes in bone marrow after any treatment time.
Conclusions:
Interpretation of results : negative
In a rat bone marrow micronucleus assay 15 males were treated via intraperitonea with Stoddard solvent at doses of
0.3, 1 and 3 g/kg. Bone marrow cells were harvested 24 hours after 48 hour treatment.
There were no signs of toxicity during the study. The positive control induced the appropriate response.
There was not a significant increase in the frequency of micronucleated polychromatic erythocytes in bone marrow after any treatment time.
Executive summary:

Mutagenicity testing of Stoddard solvent showed no evidence of genotoxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification

Justification for classification or non classification:

Based on the hazard assessment of Stoddard solvent in section 2.1 and 2.2. in IUCLID6., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99) and according to the criteria described in Directive 67/548 and in the CLP Regulation:

 

 

Directive 67/548

Mutagenicity-Genetic Toxicity

Muta. Cat. 1; R46 May cause heritable genetic damage.

Muta. Cat. 2; R46 May cause heritable genetic damage.

Muta. Cat. 3; R68 Possible risk of irreversible effects.

CLP

Germ cell mutagenicity

Muta. 1A

Muta. 1B

Muta. 2

H340: May cause genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

H341: Suspected of causing genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

 It is concluded that the substance Stoddard solvent does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity