Registration Dossier
Registration Dossier
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EC number: 215-355-9 | CAS number: 1323-42-8
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Non-genotoxic
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Envigo, Shardlow Business Park, Shardlow, Derbyshire, DE72 2GD UK
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- not specified
- Species / strain / cell type:
- E. coli WP2 uvr A
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9 metabolic fraction, 10%
- Test concentrations with justification for top dose:
- Eight concentrations of the test item (1.5, 5, 15, 50, 150, 500, 1500 and 5000 microgram/plate) were assayed in triplicate against each tester strain, using the direct plate incorporation method.
- Vehicle / solvent:
- Tetrahydrofuran
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- benzo(a)pyrene
- other:
- Details on test system and experimental conditions:
- Top agar was prepared using 0.6% Bacto agar (lot number 6147883 03/21) and 0.5% sodium chloride with 5 mL of 1.0 mM histidine and 1.0 mM biotin or 1.0 mM tryptophan solution added to each 100 mL of top agar.
In this assay, overnight sub-cultures of the appropriate coded stock cultures were prepared in nutrient broth (Oxoid Limited; lot number 1865318 05/21) and incubated at 37 °C for approximately 10 hours.
Both plate incorporation method and pre-incubation methods were used in this study.
All of the plates were incubated at 37 ± 3 degrees C for approximately 48 hours and scored for the presence of revertant colonies using an automated colony counting system. The plates were viewed microscopically for evidence of thinning (toxicity). - Evaluation criteria:
- The criteria for determining a positive result include any, one, or all of the following:
1. A dose-related increase in mutant frequency over the dose range tested (De Serres and Shelby, 1979).
2. A reproducible increase at one or more concentrations.
3. Biological relevance against in-house historical control ranges.
4. Statistical analysis of data as determined by UKEMS (Mahon et al., 1989).
5. Fold increase greater than two times the concurrent solvent control for any tester strain (especially if accompanied by an out of historical range response (Cariello and Piegorsch, 1996)).
A test item will be considered non-mutagenic (negative) in the test system if the above criteria are not met. - Statistics:
- Statistical significance was confirmed by using Dunnetts Regression Analysis (* = p < 0.05) for those values that indicate statistically significant increases in the frequency of revertant colonies compared to the concurrent solvent control.
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- A test item precipitate (white and particulate in appearance) was noted at and above 500 μg/plate, this observation did not prevent the scoring of revertant colonies.
There were no toxicologically significant increases in the frequency of revertant colonies recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 1 (plate incorporation method) or in Experiment 2 (preincubation method).
A small, statistically significant increase in TA98 revertant colony frequency was observed in the absence of S9-mix at 500 µg/plate in the first mutation test. This increase was considered to be of no biological relevance because there was no evidence of a dose-response relationship or reproducibility. Furthermore, the individual revertant colony counts at 500 µg/plate were within the in-house historical untreated/vehicle control range for the tester strain and the fold increase was only 1.4 times the concurrent vehicle control. - Conclusions:
- Naturechem® GMHS (Glyceryl Monohydroxystearate) was non-mutagenic in the Ames Assay under the conditions of this test.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- April, 1988-July, 1988
- Reliability:
- 1 (reliable without restriction)
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- According to procedures of the U.S. National Toxicology Program
- GLP compliance:
- yes
- Type of assay:
- other: in vivo micronucleus assay
- Target gene:
- not applicable. The assay assesses an increased incidence of formation of chromosomal aberrations in Chinese Hamster Ovary cells
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Cytokinesis block (if used):
- colcemid
- Metabolic activation:
- with and without
- Metabolic activation system:
- Arochlor 1254-induced S9 from male Sprague Dawley rat liver
- Test concentrations with justification for top dose:
- 5000 mg/ml, based on observation of toxicity.
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and experimental conditions:
- CHO cells were incubated with study compound or solvent. Cells were arrested in the first metaphase by addition of colcemid and harvested by mitotic shake off, fixed, and stained in 6% Giemsa. In the absence of S9, cells were incubated with study compound or solvent for 10 h at 37 deg C. Cells were then washed and fresh medium containing colcemid was added for an addiitonal 3 h followed by harvest. In the presence of S9, cells were incubated with study compound or solvent for 2 h at 37 deg C. Cells were then washed and medium without test compound was added, and incubation was continued for 10 h. Colcemid was added for the last 3 h of the incubation before harvest.
- Rationale for test conditions:
- According to the protocol of Galloway, et al., 1985, 1987.
- Statistics:
- Statistics performed on % cells with aberrations.
- Key result
- 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:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- other: not clastogenic
- Conclusions:
- The registered substance, GMHS, is considered to be non-clastogenic in a chromosomal aberrations study in Chinese Hamster Ovary cells, based on a finding of non-clastogenicity in a study on its structural analogue, castor oil, at concentrations up to 5000 mg/ml. This conclusion is adequate for the purposes of classification and labelling, and for risk assessment.
- Endpoint:
- in vitro DNA damage and/or repair study
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells)
- Principles of method if other than guideline:
- According to the method of Galloway, et al., 1985, 1987
- GLP compliance:
- not specified
- Type of assay:
- sister chromatid exchange assay in mammalian cells
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Cytokinesis block (if used):
- colcemid
- Metabolic activation:
- with and without
- Metabolic activation system:
- livers from Sprague Dawley male rats induced with Aroclor 1254
- Test concentrations with justification for top dose:
- 160, 500, 1600, 5000 µg/ml; up to limit dose.
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and experimental conditions:
- The study was performed at Environmental Health Research &Testing, Inc. A detailed description of the SCE protocol is presented by Galloway, et al., 1985, 1987. CHO cells were incubated with study compound or solvent (DMSO) and cultured for sufficient time to reach second meta phase division. Cells were collected by mitotic shake-off, fixed, air-dried and stained. The "increase over control, %" was calculated based on SCEs of the culture exposed to test compound relative to those of the culture exposed to solvent. In the absence of S9, cells were incubated with test compound for 2 hr at 37°C. Then BrdU (bromodeoxyuridine) was added and the incubation was continued for 24 h. Cells were washed, fresh medium containing BrdU and colcemid was added, and incubation was continued for 3 h. In the presence of S9, cells were incubated with test compound for 2 hr at 37°C. The cells were washed and medium containing BrdU without test material was added. Cells were incubated for a further 26 h, with colcemid present for 2-3 h.
- Rationale for test conditions:
- According to Galloway, et al., 1985, 1987.
- Statistics:
- Statistics were performed on SCE/chromosome values.
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- The registered substance, GMHS, is considered to be non-mutagenic in a sister chromatid exchange study, based on a finding of non-mutagenicity in a study on its structural analogue, castor oil in Chinese Hamster Ovary cells. This conclusion is adequate for the purposes of classification and labelling, and for risk assessment.The test substance showed no increase in sister-chromatid exchanges in an experiment by the U.S. National Toxicology Program.
Referenceopen allclose all
Experiment 1- Without metabolic activation (Plate Incorporation)
Test Period |
From: 10 March 2017- 16 March 2017 |
To: 13 March 2017- 19 March 2017 |
||||
S9-Mix (-) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
||||
Base-Pair substitution strains |
Frameshift strains |
|||||
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
||
Solvent Control (THF) |
120 101 (113) 118 10.4# |
14 15 (13) 10 2.6 |
38 41 (38) 34 3.5 |
24 23 (27) 35 6.7 |
21 12 (15) 12 5.2 |
|
1.5μg |
127 117 (123) 125 5.3 |
23 14 (17) 13 5.5 |
37 48 (44) 48 6.4 |
23 31 (31) 40 8.5 |
15 9 (14) 18 4.6 |
|
5μg |
125 118 (117) 108 8.5 |
12 18 (15) 15 3.0 |
43 45 (42) 38 3.6 |
35 33 (34) 35 3.5 |
11 17 (14) 15 3.1 |
|
15μg |
111 110 (115) 123 7.2 |
23 17 (19) 16 3.8 |
40 37 (35) 29 5.7 |
34 34 (36) 40 3.5 |
22 15 (17) 14 4.4 |
|
50μg |
110 125 (124) 137 13.7 |
8 9 (9) 10 1.0 |
46 31 (38) 37 7.5 |
35 32 (33) 33 1.5 |
12 12 (14) 19 4.0 |
|
150μg |
116 114 (120) 130 8.7 |
17 14 (14) 12 2.5 |
33 39 (36) 37 3.1 |
30 40 (34) 33 5.1 |
21 13 (17) 17 4.0 |
|
500μg |
137P 122P (124) 112P 13.5 |
13P 14P (14) 16P 1.5 |
46 P 34 P (36) 28 P 3.1 |
39P * 39P (38) 36P 4.2 |
20P 15P (17) 17P 2.5 |
|
1500μg |
115P 129P (123) 126P 7.4 |
10P 10P (10) 10P 0.0 |
32 P 24 P (36) 31 P 9.2 |
37P 31P (36) 39P 1.7 |
15P 12P (14) 14P 1.5 |
|
5000μg |
116P 113P (110) 101P 7.9 |
13P 11P (12) 11p 1.2 |
30 P 14 P (26) 33 P 10.2 |
37P 31P (34) 31P 4.6 |
12P 15P (11) 7P 4.0 |
|
Positive controls S9- Mix (-) |
Name Dose Level No. of Revertants |
ENNG |
ENNG |
ENNG |
4NQO |
9AA |
3μg |
5μg |
2μg |
0.2μg |
80μg |
||
562 580 (594) 640 40.8 |
361 430 (396) 397 34.5 |
972 1028 (997) 992 28.4 |
108 110 (114) 124 8.7 |
211 295 (274) 315 55.2 |
||
( ) concurrent negative controls
# standard deviation
* P </= 0.05
Experiment 1- With Metabolic Activation (Plate Incorporation)
Test Period |
From: 10 March 2017- 16 March 2017 |
To: 13 March 2017- 19 March 2017 |
||||
S9-Mix (-) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
||||
Base-Pair substitution strains |
Frameshift strains |
|||||
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
||
Solvent Control (THF) |
114 116 (113) 109 3.6# |
12 10 (12) 15 2.5 |
33 32 (34) 37 2.6 |
23 23 (25) 28 2.9 |
9 18 (14) 14 4.5 |
|
1.5μg |
99 99 (104) 113 8.1 |
7 13 (10) 11 3.1 |
35 42 (35) 28 7.0 |
39 29 (32) 29 5.8 |
14 10 (13) 14 4.5 |
|
5μg |
103 106 (106) 110 3.5 |
11 11 (11) 12 0.6 |
28 27 (31) 37 5.5 |
28 23 (25) 25 2.5 |
14 8 (11) 12 3.1 |
|
15μg |
107 124 (124) 142 17.5 |
11 12 (10) 8 2.1 |
24 41 (32) 31 8.5 |
33 36 (32) 28 4.0 |
18 15 (15) 11 3.5 |
|
50μg |
121 135 (127) 126 7.1 |
11 12 (12) 13 1.2 |
27 29 (29) 31 2.0 |
21 27 (29) 38 8.6 |
9 18 (14) 16 4.7 |
|
150μg |
132 129 (131) 131 1.5 |
11 19 (14) 12 4.4 |
29 31 (31) 33 2.0 |
21 28 (24) 22 3.8 |
15 14 (14) 13 1.0 |
|
500μg |
115P 118P (119) 125P 5.1 |
19P 12P (11) 10P 1.2 |
37P 31P (33) 32P 3.2 |
18P 32P (30) 39P 10.7 |
15P 11P (13) 12P 2.1 |
|
1500μg |
101P 134P (112) 101P 19.1 |
9P 14P (11) 10P 2.6 |
33P 19P (30) 38P 9.8 |
20P 27P (26) 32P 6.0 |
11P 9P (9) 7P 2.0 |
|
5000μg |
117P 104P (109) 106P 7.0 |
12P 10P (12) 14P 2.0 |
33P 33P (30) 25P 4.6 |
26P 26P (24) 21P 2.9 |
10P 11P (10) 9P 1.0 |
|
Positive controls S9- Mix (-) |
Name Dose Level No. of Revertants |
2AA |
2AA |
2AA |
BP |
2AA |
1μg |
2μg |
10μg |
5μg |
2μg |
||
1940 1883 (1850) 1727 110.3 |
289 264 (264) 240 24.5 |
271 374 (347) 395 66.4 |
225 199 (217) 228 15.9 |
402 396 (416) 451 30.2 |
||
( ) Concurrent negative controls
# Standard deviation
P Precipitate
Experiment 2- Without metabolic activation (Pre-Incubation)
Test Period |
From: 24 March |
To: 27 March |
||||
S9-Mix (-) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
||||
Base-Pair substitution strains |
Frameshift strains |
|||||
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
||
Solvent Control (THF) |
91 92 (89) 85 3.8# |
14 9 (11) 11 2.5 |
35 37 (38) 43 4.2 |
13 21 (18) 20 4.4 |
8 13 (10) 8 2.9 |
|
15μg |
89 86 (92) 102 8.5 |
8 8 (8) 9 0.6 |
32 28 (32) 36 4.0 |
15 21 (16) 12 4.6 |
4 8 (8) 11 3.5 |
|
50μg |
83 78 (79) 73 4.0 |
8 10 (9) 9 1.0 |
33 42 (40) 44 5.9 |
18 14 (17) 19 2.6 |
11 5 (8) 8 3.0 |
|
150μg |
83 88 (85) 85 2.5 |
9 9 (9) 8 0.6 |
40 36 (39) 41 2.6 |
21 22 (21) 19 15 |
8 10 (8) 7 1.5 |
|
500μg |
101P 86P (93) 92P 7.5 |
14P 10P (12) 11P 2.1 |
40P 33P (37) 37P 3.5 |
16P 19P (20) 25P 4.6 |
12P 7P (9) 9P 2.5 |
|
1500μg |
88P 96P (90) 86P 5.3 |
10P 12P (11) 11P 1.0 |
40P 35P (39) 42P 3.6 |
21P 19P (19) 17P 2.0 |
13P 11P (11) 8P 2.5 |
|
5000μg |
94P 79P (88) 90P 7.8 |
9P 12P (10) 9P 1.7 |
34P 37P (34) 30P 3.5 |
21P 19P (21) 22P 1.5 |
10P 7P (10) 12P 2.5 |
|
Positive controls S9- Mix (-) |
Name Dose Level No. of Revertants |
ENNG |
ENNG |
ENNG |
4NQO |
9AA |
3μg |
5μg |
2μg |
0.2μg |
80μg |
||
511 542 (547) 588 38.7 |
193 190 (192) 193 1.7 |
283 248 (269) 276 18.5 |
190 191 (191) 192 1.0 |
387 213 (274) 223 97.7 |
||
( ) concurrent negative controls
# Standard deviation
P Precipitate
Experiment 2- With Metabolic Activation (Pre-Incubation)
Test Period |
From: 24 March |
To: 27 March |
||||
S9-Mix (-) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
||||
Base-Pair substitution strains |
Frameshift strains |
|||||
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
||
Solvent Control (THF) |
96 95 (96) 98 1.5# |
7 12 (12) 17 5.0 |
47 37 (37) 27 10.0 |
40 27 (28) 17 11.5 |
9 9 (8) 7 1.2 |
|
15μg |
103 104 (103) 103 0.6 |
16 9 (13) 14 3.6 |
38 38 (38) 38 0.0 |
26 18 (28) 40 11.1 |
9 5 (9) 13 4.0 |
|
50μg |
84 92 (89) 92 4.6 |
9 10 (11) 14 2.6 |
39 31 (36) 37 4.2 |
28 17 (24) 28 6.4 |
3 9 (7) 8 3.2 |
|
150μg |
91 97 (94) 93 3.1 |
15 7 (12) 14 4.4 |
47 34 (42) 44 6.8 |
20 22 (24) 28 6.4 |
15 9 (10) 7 4.2 |
|
500μg |
97P 91P (92) 88P 4.6 |
10P 12P (12) 14P 2.0 |
34P 45P (39) 39P 5.5 |
27P 30P (29) 30P 1.7 |
12P 8P (9) 7P 2.6 |
|
1500μg |
101P 95P (96) 91P 5.0 |
11P 10P (11) 13P 1.5 |
36P 44P (40) 41P 4.0 |
29P 26P (26) 24P 2.5 |
10P 6P (9) 11P 2.6 |
|
5000μg |
90P 97P (93) 93P 3.5 |
14P 12P (12) 11P 1.5 |
32P 39P (37) 41P 4.7 |
22P 23P (25) 29P 3.8 |
10P 9P (9) 7P 1.5 |
|
Positive controls S9- Mix (-) |
Name Dose Level No. of Revertants |
2AA |
2AA |
2AA |
BP |
2AA |
1μg |
2μg |
10μg |
5μg |
2μg |
||
1785 1819 (1725) 1570 135.0 |
270 276 (272) 270 3.5 |
257 209 (238) 248 25.5 |
120 108 (116) 120 6.9 |
248 271 (264) 272 13.6 |
||
( ) Concurrent negative controls
# Standard deviation
P Precipitate
| Induction of Chromosomal Aberrations in CHO Cells by Castor Oil | |||||||||
| Without S9 | With S9 | ||||||||
| Dose (mg/ml) | Total Cells | No. of Abs. | Abs./cell | % Cells with Abs. | Dose (mg/ml) | Total Cells | No. of Abs. | Abs./cell | % Cells with Abs. |
| Harvest time: 12 h | Harvest time: 13 h | ||||||||
| DMSO | 200 | 2 | 0.01 | 1 | DMSO | 200 | 3 | 0.02 | 1.5 |
| Castor Oil | Castor Oil | ||||||||
| 1600 | 200 | 1 | 0.01 | 0.5 | 1600 | 200 | 4 | 0.02 | 2.0 |
| 3000 | 200 | 2 | 0.01 | 1 | 3000 | 200 | 4 | 0.02 | 2.0 |
| 5000 | 200 | 1 | 0.01 | 0.5 | 5000 | 200 | 3 | 0.02 | 1.5 |
| Summary: Negative | Summary: Negative | ||||||||
| Mitomycin-C | Cyclophosphamide | ||||||||
| 0.0625 | 200 | 48 | 0.24 | 15.5 | 2.5 | 200 | 44 | 0.22 | 16.0 |
| 0.25 | 50 | 16 | 0.32 | 26.0 | 7.5 | 50 | 18 | 0.36 | 30.0 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
non-genotoxic
Link to relevant study records
- 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
- Study period:
- April, 1988-July, 1988
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study by GLP
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Animals weight-randomized into groups by sex, assigned to cages and cages assigned to dose groups. Mice were caged individually.
Animals obtained from Simonsen Laboratories, Gilroy CA, USA
Animal room temperature: 68-76 degrees F, relative humidiay 42-72%.
Fluorescent light 12 h/day, 10 room air changes/hour.
Age at initiation of study: 6 weeks
Quaranteed 15 days prior to study. - Route of administration:
- oral: feed
- Vehicle:
- NIH 07, available ad libitum
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): Prepared every 21 days. Feed within animal cages was changed every 3 days.
- Mixing appropriate amounts with (Type of food): NIH07, ad lib
- Storage temperature of food: at 5degrees C, in the dark
VEHICLE
- Justification for use and choice of vehicle (if other than water): NIH07, ad lib - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- ad libitum
- Post exposure period:
- not applicable; test is performed on peripheral blood from a subchronic study.
- Dose / conc.:
- 0.62 other: % in diet
- Remarks:
- Doses / Concentrations:
0, 0.62%, 1.25%, 2.5%, 5.0% and 10%
Basis:
nominal conc. - Dose / conc.:
- 1.25 other: % in diet
- Dose / conc.:
- 2.5 other: % in diet
- Dose / conc.:
- 5 other: % in diet
- Dose / conc.:
- 10 other: % in diet
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, plain diet
- Positive control(s):
- Urethane (0.2%) was used as a positive control. Three male mice were dosed for 4 weeks with this positive control in the drinking water.
- Tissues and cell types examined:
- Peripheral blood, obtained at sacrifice from cardiac puncture.
- Details of tissue and slide preparation:
- Slides were stained with Hoechst 33258/pyronin Y, according to the method of MacGregor, et al., 1983). At least 2000 PCE and 10,000 NCE from each animal were scored for micronuclei.
- Statistics:
- Values are Mean +/- Standard Error of the Mean. Significant differences were assessed using Shirley's test (Shirley, 1977), at p <0.05.
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Remarks:
- no increase in micronucleated erythrocytes
- Toxicity:
- no effects
- Remarks:
- no adverse hematologic effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- No significant elevation in the frequency of micronucleated erythrocytes was observed in either male or female mice administered castor oil in dosed feed.
- Conclusions:
- Castor oil, when administered in the feed to B6C3F1 mice for 13 weeks, did not result in an increase in micronucleated erythrocytes. The substance is not a genotoxicant, under the conditions of the study.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
An Ames assay on the registered substance was negative, non-mutagenic, and consistent with the findings of studies on other structural analogues. Additional genotoxicity testing, both in vitro and in vivo (micronucleus assay), were negative on a structural analogue, castor oil. The consulting group DHI, charged on behalf of ECHA with evaluating the legitimacy of REACH Annex IV lists, concluded that castor oil is appropriate for listing on Annex IV and is exempt from the obligation to register. This supports the position that additional genotoxicity testing is not indicated for this and similarly structured analogue substances.
Justification for classification or non-classification
There was no evidence of genotoxicity in any studies on the registered material or on the structural analogues. DHI, consultants for ECHA, reviewed the data on the analogue substance, castor oil, for inclusion on Annex IV and concluded that these data, including genotoxicity data, were sufficient to conclude that the substance presents no hazard requiring additional studies. The criteria for classification as a genotoxicant according to Regulation EC No. 1272/2008 are not met, and the substance is not classified.
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