Glycerides, C16-18 and C18-unsatd. mono-

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

27 Nov 1984 -20 Dec 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study with acceptable restrictions. Lack of test material details. Only the highest dose group was evaluated.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

lack of test material details; only the highest dose group was evaluated

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Glycerides, C16-18 and C18-hydroxy mono- and di-

EC Number:

295-191-2

EC Name:

Glycerides, C16-18 and C18-hydroxy mono- and di-

Cas Number:

91845-19-1

IUPAC Name:

91845-19-1

Details on test material:

- Name of test material (as cited in study report): only trade name given
- Chemical denomination: Glyceride, C16-18 und C18 mono- und dihydroxyfettsäuren
- Physical state: white solid
- Analytical purity: no data
- Analytical data: melting point: 94 °C; acid value: 1.0; saponification value: 178; hydroxyl value: 138; iodine value: 3.4; epoxy oxygen content: 0.4%

Test animals

Species:

mouse

Strain:

other: CFW 1 (Winkelmann)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: 21-29 g
- Fasting period before study: animals were fasted at least 4 h prior to administration.
- Housing: male animals were housed individually in Makrolon cages type I, female animals were housed in groups up to 4 animals in Makrolon cages type II
- Diet: Haltungsdiät Altromin 1324, 10 mm pellets (Altrogge Spezialfutter), feeding frequency not further specified
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: peanut oil Oleum Arachidis G166/DAB 8
- Amount of vehicle: 20 mL/kg bw

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
An aliquot of the test substance was molten at 70 ºC and mixed with 70 ºC warm peanut oil. After cooling of the solution, the mixture was applicated by oral gavage.

Duration of treatment / exposure:

single application

Frequency of treatment:

single application

Post exposure period:

24, 48 and 72 h after treatment

Doses / concentrations

Remarks:

Doses / Concentrations:
1000, 5000 and 10000 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

Preliminary study: 2
Main study: 7

Control animals:

yes, concurrent vehicle

Positive control(s):

- Cyclophosphamide
- Route of administration: intraperitoneal injection
- Doses / concentrations: 10 mg/kg bw in water

Examinations

Tissues and cell types examined:

Tissue: femoral bone marrow
Cell type: erythrocytes of the bone marrow

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
Slides were fixed with methanol and stained with Giemsa-solution for 10 min.

METHOD OF ANALYSIS: 1 slide per animal was analysed. The number of micronuclei was counted in 1000 polychromatic erythrocytes per animal and the ratio of polychromatic and normochromatic erythrocytes was recorded.

Statistics:

Mean values and standard deviations were calculated. For calculation of significances the tables of Kastenbaum and Bowman (Kastenbaum, M.A. and Bowman, K.O., 1970, Mutation Research 9:527-549) were used.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

Animals of all dose groups showed reduced activity and ruffled fur.

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: 5000, 7500 and 10000 mg/kg bw
- Clinical signs of toxicity in test animals: In the mid dose-group slightly reduced activity and ruffled fur was observed up to 20 h after application. In the high dose-group all animals showed slightly reduced activity, in male animals strongly ruffled fur and in female animals slightly ruffled fur was observed. No clinical signs of systemic toxicity were observed after 48 h.

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei: no significant increase of micronuclei number was observed
- Ratio of PCE/NCE: no influence of the test material was observed in comparison to the controls
- Clinical signs of toxicity in test animals: In the low dose-group slightly reduced activity after application was observed and in the mid dose-group slightly reduced activity and ruffled fur was observed after application. No clinical signs of toxicity were observed after 24 h. In the high dose-group all animals showed slightly reduced activity and strongly ruffled fur. No clinical signs of systemic toxicity were observed after 20 h.

Any other information on results incl. tables

No deaths occured during the study. As there were no indications for genotoxicity in animals dosed with 10000 mg/kg bw, analysis of micronuclei was not performed in animals dosed with 1000 and 5000 mg/kg bw.

Table 1: Results of the in vivo micronucleus assay in male animals

Exp group	Number of animals	Sampling time (h after administration)	Dose [mg/kg bw]	Mean PCEs/NCEs at sampling time	Total micronuclei per 1000 PCEs at sampling time
					mean values	range
Vehicle control (peanut oil)	7	24	20 mL/kg	1.11	1.57	0-2
Positive control (cyclophosphamide)	7	24	10	1.10	7.71	4-11
Test substance	7	24	10000	1.20	2.14	1-4
Test substance	7	48	10000	1.00	1.00	0-2
Test substance	7	72	10000	1.25	1.43	0-3

  

Table 2: Results of the in vivo micronucleus assay in female animals

Exp group	Number of animals	Sampling time (h after administration)	Dose [mg/kg bw]	Mean PCEs/NCEs at sampling time	Total micronuclei per 1000 PCEs at sampling time
					mean values	range
Vehicle control (peanut oil)	7	24	20 mL/kg	1.26	1.14	0-3
Positive control (Cyclophosphamide)	7	24	10	1.15	6.86	4-10
Test substance	7	24	10000	1.07	2.00	1-4
Test substance	7	48	10000	1.06	2.29	0-6
Test substance	7	72	10000	1.15	1.86	0-3

PCE = polychromatic erythrocytes

NCE = norchromatic erythrocytes

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative