Resin acids and Rosin acids, fumarated, compds. with triethanolamine

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 from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted comparable to OECD guideline tested with the source substance CAS 102-71-6. Based on the structural similarities and the fact that the target substance is an adduct of the source substance, this study is considered valid for read-across.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

treatmant of animals for 13 prior to blood sampling

Principles of method if other than guideline:

According to standard NTP protocol

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2,2',2''-nitrilotriethanol

EC Number:

203-049-8

EC Name:

2,2',2''-nitrilotriethanol

Cas Number:

102-71-6

IUPAC Name:

2,2',2''-nitrilotriethanol

Test material form:

solid - liquid: suspension

Details on test material:

Name of test material (as cited in study report): Triethanolamine
- Physical state: clear, colorless, viscous liquid
- Analytical purity: 99%
- Impurities (identity and concentrations): <0.5% water; <.4% primary or secondary amines
- Lot/batch No.: Lot 3B-1-84
- Storage condition of test material: Neat chemical stored at room temperature; triethanolamine:acetone mixtures stored at 5°C, protected from light

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories (Gilroy, CA)
- Age at study initiation: 6 weeks old
- Weight at study initiation: mean 23 g (males), 19 g (females)
- Housing: individually in Polycarbonate (Lab Products, Inc., Garfield, NJ), changed weekly, with bedding of Beta-Chips® hardwood chips (Northeastern Products, Inc., Warrensburg, NY), changed weekly
- Diet (e.g. ad libitum): NIH-07 open formula pelleted diet (Zeigler Brothers, Inc.,Gardners, PA), available ad libitum, changed weekly
- Water (e.g. ad libitum): Tap water (City of Columbus municipal supply) via automatic watering system (Edstrom Industries, Waterford, WI), available
ad libitum
- Acclimatization: 11 to 14 da

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 - 23.9
- Humidity (%): 35 - 65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 30 June 1986 To:14 November 1986

Administration / exposure

Route of administration:

dermal

Vehicle:

- Vehicle(s)/solvent(s) used: Acetone

Details on exposure:

TEST SITE
- Area of exposure: area extending from the animal’s mid-back to the dorsal intrascapular region
- Time intervals for shavings or clipplings: clipped weekly


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): if the dose volume exceeded 320 μL, half the total volume was administered in the morning and the
remainder was administered in the afternoon
- Concentration (if solution): 0, 125, 250, 500, 1,000, or 2,000 mg/kg bw
- Constant volume or concentration used: yes

VEHICLE
- Justification for use and choice of vehicle (if other than water): Acetone is miscible with triethanolamine and because acetone rapidly evaporates.

USE OF RESTRAINERS FOR PREVENTING INGESTION: no

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily, 5 days/week

Post exposure period:

none

Doses / concentrations

Remarks:

Doses / Concentrations:
500, 1,000, 2,000, 4000 mg/kg bw
Basis:
other: nominal per unit body weight

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Examinations

Tissues and cell types examined:

Peripheral blood samples

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION
Doses were based on a 14-a nd 16-day study, where skin irritation was observed with higher doses.

DETAILS OF SLIDE PREPARATION:
Smears were immediately prepared and fixed in absolute methanol and were later stained with a chromatin-specific fluorescent dye mixture of Hoechst 33258/pyronin Y (MacGregor et al., 1983)

METHOD OF ANALYSIS:
Slides were scanned to determine the frequency of micronuclei in 2000 polychromatic erythrocytes (PCEs) and 10000 normochromatic erythrocytes (NCEs) in each animal per dose group.

Statistics:

Log transformation of the NCE data, testing for normality by the Shapiro-Wilk test, and testing for heterogeneity of variance by Cochran’s test were performed before statistical analyses. The frequency of micronucleated cells among NCEs was analyzed by analysis of variance using the SAS GLM procedure. The NCE data for each dose group were compared with the concurrent solvent control with a Student’s t-test. The frequency of micronucleated cells among PCEs was analyzed by the Cochran-Armitage trend test, and individual dose groups were compared to the concurrent solvent control by Kastenbaum-Bowman’s binomial test.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

animals of high dose groups showed acanthosis and inflammation at the site of application were observed in both males and females at 4000 mg/kg bw per day, and liver and kidney weights were increased at that dose.

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

not examined

Any other information on results incl. tables

Results:

Sex	Sample Collection Time	Dose (g/kg)	Animal Number	Normochromatic Erythrocytes
				Trend P: 0.42
Male	24 hour			No. Examined	Total MN Cells	Percent NCE	MN Cells
							per 1000
Vehicle Control	Acetone	0	11	20		1.4
		0	12	23		2
		0	13	29		2.2
		0	14	38		3.2
		0	15	14		1.1
		0	16	17		1.5
		0	17	20		1.7
		0	18	27		2
		0	19	15		1.2
		0	20	13		1.2
Average ± SEM						±	1.75 ± 0.20
Test Chemical	Triethanolamine	1	71	22		2.2
		1	72	18		1.8
		1	73	21		1.8
		1	74	21		1.6
		1	75	36		2.9
		1	76	22		1.6
		1	77	25		2.4
		1	78	21		1.8
		1	79	20		1.9
		1	80	8		0.8
Average ± SEM						±	1.88 ± 0.17
Pairwise P							0.3138
Test Chemical	Triethanolamine	2	100	15		1.2
		2	91	18		1.5
		2	92	15		1.5
		2	93	18		1.8
		2	94	11		1.1
		2	95	15		1.2
		2	96	11		1
		2	97	18		1.6
		2	98	22		1.7
		2	99	14		1
Average ± SEM						±	1.35 ± 0.10
Pairwise P							0.935
Test Chemical	Triethanolamine	4	111	18		1.5
		4	112	30		2.2
		4	113	18		1.7
		4	114	11		1
		4	115	19		1.7
		4	116	25		1.9
		4	117	14		1.4
		4	118	17		1.4
		4	119	19		1.7
		4	120	46		4.5
Average ± SEM						±	1.89 ± 0.30
Pairwise P							0.3047

Sex	Sample Collection Time	Dose (g/kg)	Animal Number	Normochromatic Erythrocytes
				Trend P: 0.925
Female	24 hour			No. Examined	Total MN Cells	Percent NCE	MN Cells
							per 1000
Vehicle Control	Acetone	0	131	10		0.8
		0	132	25		2
		0	133	10		1
		0	134	13		1.1
		0	135	11		0.9
		0	136	10		0.8
		0	137	12		1.1
		0	138	13		1.1
		0	139	12		1.1
		0	140	18		1.7
Average ± SEM						±	1.16 ± 0.12
Test Chemical	Triethanolamine	1	191	17		1.5
		1	192	20		1.5
		1	193	16		1.6
		1	194	12		1.2
		1	195	15		1.2
		1	196	9		0.9
		1	197	13		1
		1	198	15		1.1
		1	199	13		1.2
		1	200	10		0.9
Average ± SEM						±	1.20 ± 0.08
Pairwise P							0.389
Test Chemical	Triethanolamine	2	211	18		1.8
		2	212	10		0.7
		2	213	9		0.9
		2	214	13		1.1
		2	215	17		1.2
		2	216	16		1.4
		2	217	8		0.8
		2	218	16		1.5
		2	219	9		0.7
		2	220	7		0.7
Average ± SEM						±	1.07 ± 0.12
Pairwise P							0.7393
Test Chemical	Triethanolamine	4	231	8		0.8
		4	232	14		1.3
		4	233	11		1
		4	234	12		1
		4	235	4		0.4
		4	236	11		0.9
		4	237	21		1.7
		4	238	9		0.8
		4	239	12		1.1
		4	240	13		1.1
Average ± SEM						±	1.00 ± 0.11
Pairwise P							0.8813

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Treatment of male and female mice with triethanolamineup to 4000 mg/kg bw/d for 13 weeks by dermal application did not result in any change in the frequency of micronuclei in their blood cells.

Executive summary:

Male and female B6C3F mice were treated dermally with triethanolamine up to 4000 mg/kg bw/d for 13 weeks. Analysis of periperhal blood cells after the application period did don reveal any change in the frequency of micronuclei when compared with untreated control animals. Thus, no in vivo mutagenicity could be shown for triethanolamine.

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