Glycine

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Test procedures in accordance with accepted standard methods, insufficiently documentation, statistical method not described.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1977

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Rats were treated with the test substance subcutaneously for 30 days.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycine

EC Number:

200-272-2

EC Name:

Glycine

Cas Number:

56-40-6

Molecular formula:

C2H5NO2

IUPAC Name:

glycine

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 weeks old
- Weight at study initiation: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2 ℃
- Humidity (%): 55 +/- 5 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

physiological saline

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

30 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

1 500 mg/kg bw/day

No. of animals per sex per dose:

male and female each 10 rats/group

Control animals:

yes, concurrent vehicle

Details on study design:

In this study, egg albumin was also used as a test substance, but the data of the egg albumin were omitted.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes

FOOD CONSUMPTION: No data

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- How many animals: 5 animals

CLINICAL CHEMISTRY: Yes
- How many animals: 5 animals

URINALYSIS: Yes

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
- How many animals: 5 animals

HISTOPATHOLOGY: Yes
- How many animals: 5 animals

Other examinations:

no

Statistics:

Statistics was used, but the method was not descibed in the article.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY:
No deaths were observed in all groups. At the begining of the dosing period, spontaneous locomotion, respiratory depression and ptosis were observed in both sexes receiving glycine (1500 mg/kg) from ca. 20 minutes after dosing till 3 or 4 hours later. These signs almost disappeared 10 days after dosing. Hardening or necrosis was observed at the injection site of the test substance treated groups and progressed to marked necrosis by the end of the injection period.

BODY WEIGHT AND WEIGHT GAIN: no effects

FOOD CONSUMPTION: The food consumption in the males of the 1500 mg glycine/kg group was temporarily slightly less than in the control group.

FOOD EFFICIENCY: not examined

WATER CONSUMPTION: not examined

OPHTHALMOSCOPIC EXAMINATION: not examined

HAEMATOLOGY:
The number of white blood cells was significantly increased in both sexes of the 1500 mg/kg bw/d dose group. Differential count of neutrophils in females of the high dose group was significantly increased and lymphocytes were significantly decreased when compared to controls. In males of the 100 mg/kg bw/d dose group, differential count of neutrophils was significantly increased and lymphocytes were significantly decreased when compared to controls.

CLINICAL CHEMISTRY: no effects

URINALYSIS: no effects

NEUROBEHAVIOUR: not examined

ORGAN WEIGHTS: Significantly increased weights of spleen were observed in both sexes in the 1500 mg glycine/kg group.

GROSS PATHOLOGY: no effects

HISTOPATHOLOGY: NON-NEOPLASTIC:
Slight cell infiltration in peri-bronchus, liver (glisson's sheath, hepatic lobule) or kidney, bile duct proliferation or sinusoidal dilatation in liver, vacuolation in adrenal gland, extramedullary hematopoiesis in spleen were observed among control and treated groups. No abnormal findings were found in brain, heart, pancreas, stomach, duodenum, rectum, femur, testis and ovary.

HISTOPATHOLOGY: NEOPLASTIC: no effects

Effect levels

1

Dose descriptor:

LOAEL

Effect level:

1 500 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

2

Dose descriptor:

NOAEL

Effect level:

100 - 1 500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

In both sexes receiving glycine, no deaths were found and the body weight gains were normal compared to the control groups during the dosing period. Necrosis were observed at injection sites in the glycine groups. Especially, in males and/or females received 1500 mg glycine/kg, increased number of white blood cells and of differential count of neutrophils, and increased spleen weight were detected, indicating the non-specific irritation caused by glycine. No histological findings were also detected in the glycine groups. See Tables 1 and 2.

      

Table 1. Hematological examination

Sex		Dose(mg/kg)	Erythrocyte	Leucocyte	Hemoglobin	Hemogramm	%
			x 10^4/mm^3	x 10^2/mm^3	Sahli %	Neutrophil	Lymphocyte
Male	Control (saline)	0	1081 +/- 49.9	103 +/- 8.1	99 +/- 3.1	12	87
	Glycine	100	1014 +/- 51.4	107 +/- 7.0	95 +/- 1.4	*26	*71
	Glycine	1500	1167 +/- 31.0	*184 +/- 14.4	90 +/- 0.5	22	76
Female	Control (saline)	0	1119 +/- 51.5	89 +/- 9.5	103 +/- 1.7	11	88
	Glycine	100	1060 +/- 28.6	118 +/- 2.0	89 +/- 1.9	11	89
	Glycine	1500	1167 +/- 60.0	*181 ± 6.7	100 ± 2.9	*24	*73

*Significant difference from the control (P<0.05)

      

      

Table 2. Ogan weights

Sex	Group	Dose(mg/kg)	Spleen (g)
Male	Control (saline)	0	0.78 +/- 0.09
	Glycine	100	0.96 +/- 0.30
	Glycine	1500	*1.16 +/- 0.18
Female	Control (saline)	0	0.63 +/- 0.15
	Glycine	100	0.78 +/- 0.25
	Glycine	1500	*1.13 +/- 0.25

*Significant difference from the control (P<0.05)