2,2',2''-nitrilotriethanol citrate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

GLP compliance:

no

Limit test:

no

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

Molecular formula:

C6H15NO3

IUPAC Name:

2,2',2''-nitrilotriethanol

Test material form:

liquid: viscous

Specific details on test material used for the study:

- Name of test material (as cited in study report): triethanolamine
- Analytical purity: 88.5%
- Impurities (identity and concentrations): MEA<0.12; DEA 6.0; TEA-1EO 5.3

Test animals

Species:

rat

Strain:

other: Cox CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

- 20 male and 20 female per group
- Diet: ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: standard chow

Duration of treatment / exposure:

91 days

Frequency of treatment:

continuously

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

250 other: mg/kg bw

Doses / concentrations 2

Dose / conc.:

500 other: mg/kg bw

Doses / concentrations 3

Dose / conc.:

1 000 other: mg/kg bw

No. of animals per sex per dose:

20

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: no

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
FOOD EFFICIENCY: Yes
HAEMATOLOGY: Yes

Sacrifice and pathology:

HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

One male from the mid-dose group and one female from the low-dose group displayed symptoms of inner ear infection.

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

The only adverse significant differences noted were in body weight gain in the female rats of the mid-dose group.
Please see the Table 1. in Section "Any other information on results incl. tables"

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Please see the Table 2. in Section "Any other information on results incl. tables"

Food efficiency:

effects observed, non-treatment-related

Description (incidence and severity):

The only adverse significant differences noted were in feed efficiency in the female rats of the mid-dose group.
Please see the Table 3. in Section "Any other information on results incl. tables"

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

The only abnormality observed was a slightly elevated WBC in one animal. This change was not considered significant. All other values are within normal limits and there were no significant differences between treatment groups.

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

Please see the Table 4. and 5. in Section "Any other information on results incl. tables"

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

Tissue alterations observed were mild and were not considered significant. No lesions were found which followed a pattern of agent-induced toxicity.

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 000 other: mg/kg bw

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no significant effects at highest dose tested

Target system / organ toxicity

Critical effects observed:

no

Any other information on results incl. tables

Additiononal information: One rat escaped from its cage during the third week of the test and had to be eliminated because of contamination.

Table 1. Bodyweight gain

	males	females
Control	341±30	157±23
250 mg/kg	339±35	170±13
500 mg/kg	331±28	151±15
1000 mg/kg	329±32	161±22

 

Table 2. Feed consumption

	males	females
Control	2143±155	1542±105
250 mg/kg	2073±165	1592±108
500 mg/kg	2076±282	5166±115
1000 mg/kg	2091±155	1604±123

 

Table 3. Feed efficiency

	males	females
Control	15.95±0.98	10.18±1.1
250 mg/kg	16.35±0.97	10.72±0.67
500 mg/kg	15.56±0.84	8.62±2.7
1000 mg/kg	15.75±0.99	9.99±0.88

   

Table 4. Organ to bodyweight ratio (LIVER)

	males	females
Control	38.2±3.3	42.1±12.2
250 mg/kg	41.6±3.7	39.9±3.3
500 mg/kg	45.9±6.9	44.6±1.0
1000 mg/kg	49.6±2.9	45.3±2.9

 

Table 5. Organ to bodyweight ratio (KIDNEY)

	males	females
Control	7.6±0.6	8.1±0.3
250 mg/kg	9.3±1.3	10.2±1.4
500 mg/kg	9.2±0.7	11.1±0.7
1000 mg/kg	10.4±1.4	10.3±1.4