2-methyl-p-phenylenediamine sulfate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given, comparable to guideline/standards

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Principles of method if other than guideline:

Acute oral toxicity or LD50 value was determined by oral administration of test substance to five dose groups of rats. Subsequently, observations of effects such as clinical signs, cage side observation and mortality are made for 14 d. The test method employed in this study is comparable to OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

pre-dates GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl-p-phenylenediamine

EC Number:

202-442-1

EC Name:

2-methyl-p-phenylenediamine

Cas Number:

95-70-5

Molecular formula:

C7H10N2

IUPAC Name:

2-methylbenzene-1,4-diamine

Constituent 2

Reference substance name:

2-methyl-1,4-benzenediamine

IUPAC Name:

2-methyl-1,4-benzenediamine

Details on test material:

- Name of test material: Toluene-2, 5-diamine
- Molecular formula: Not reported
- Molecular weight: Not reported
- Substance type: Pure active substance
- Physical state: Not reported

Test animals

Species:

rat

Strain:

other: CFY strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: 98-120 g
- Fasting period before study: Overnight before treatment
- Housing: Not reported
- Diet: Not reported
- Water: Not reported
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS: No details on environmental condition were provided in the report

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous sodium sulphite (0.05%)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10% Toluene-2, 5-diamine
- Amount of vehicle: 2.5 mL/kg bw
- Justification for choice of vehicle: Not reported
- Lot/batch no.: Not reported
- Purity: Not reported

MAXIMUM DOSE VOLUME APPLIED: 0.64-2.5 mL/kg bw

DOSAGE PREPARATION: 10% solution of test substance was prepared in aqueous sodium sulphite (0.05%)

Doses:

0, 64, 100, 160, and 250 mg/kg bw

No. of animals per sex per dose:

Five males and five females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Daily for 14 days, body weights were taken prior to dosing, and on 7th and 14th day of dosing.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs of toxicity, mortality, Autopsy of animals died during the study.

Statistics:

The LD50 and its 95% confidence limits were calculated by the method of Weil C.S. (1952) Biometrics 8, 249.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

102 mg/kg bw

Based on:

test mat.

95% CL:

69 - 152

Mortality:

3/5 males and 0/5 females at 64 mg/kg
4/5 males and 3/5 females at 100 mg/kg
0/5 males and 5/5 females at 160 mg/kg
5/5 males and 4/5 females at 250 mg/kg

No mortality with vehicle control

Clinical signs:

other: Signs of reaction to treatment, observed shortly after dosing, which included: lethargy, piloerection, ataxia and increased salivation. These sign were accompanied by increased respiratory rate in rats treated at 100mg/kg and decreased respiratory rate in

Gross pathology:

Mortality was observed within 1 h to 22 h of treatment. Autopsy of these animals revealed slight heamorrhage of the lungs, pallor of the spleen, darkening of the liver and injection of peritoneal blood vessels.

Terminal autopsy findings were normal

Other findings:

- Recovery of animals: Recovery of survivors, as judged by external appearance and behavior, was apparently complete within 5 days of treatment.

- Organ weights: Not reported
- Histopathology: Not reported
- Potential target organs: Not reported

Any other information on results incl. tables

Table1: Mortality data for group of rats dosed orally with toluene-2,5-diamine (range finding study) (study # 71169)

Dosage (mg/kg bw)	Mortality ratio (no. of deaths/no. of animal dosed)			Time of death after dosing
	Male	Female	Combined
0	0/2	0/2	0/4	-
64	0/2	0/2	0/4	-
250	2/2	1/2	3/4	<21 h
1000	2/2	2/2	3/4	<2 h

- The result of preliminary range finding study indicated that median lethal oral dose (LD50) was in range of 64 to 250 mg/kg bw

Table 2: Mortality ratio and of group mean bw (g) of rats dosed orally with toluene-2,5-diamine (study # 71169)

Sex	Dosage	Bodyweight (g) at			Mortality ratio (no. of deaths/no. of animal dosed)	Time of death after dosing
		Dosing	1 wk	2 wk
Male	0	101	177	222	0/5
	64	112	178	229	3/5	< 22 h
	100	102	167	234	4/5	< 2 h
	160	116	174	242	0/5
	250	106	Died		5/5	< 21 h
Female	0	106	153	171	0/5
	64	113	148	172	0/5
	100	107	136	174	3/5	< 2
	160	104	Died		5/5	< 22
	250	106	152	180	4/5	< 21

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 of Toluene-2, 5-diamine in 0.05% aqueous sodium sulphite vehicle was determined to be 102 mg/kg bw (95% CI= 69-150 mg/kg bw).

Executive summary:

The acute oral toxicity of Toluene-2, 5-diamine was determined following OECD Guideline 401 (Acute Oral Toxicity)

The study was designed to determine acute oral LD50 of Toluene-2, 5-diamine in 0.05% aqueous sodium sulphite vehicle when dosed to group of rats by oral gavage.

The study involved 5 groups of 10 rats each (5 males / 5 females) weighing 98 to 120 g, starved overnight before treatment with group specific concentration (0, 64, 100, 160 and 250 mg/kg bw) of Toluene-2, 5-diamine.

The selection of various concentrations was based on results from preliminary (range finding) study which indicated that median lethal oral dose (LD50) was in range of 64 to 250 mg/kg bw.

Post treatment, rats were observed for 14 days to record mortality and signs of toxicity. All rats that died during observation period were examined macroscopically to identify the target organ and those surviving were sacrificed terminally to detect possible residual damage.

Signs of toxicity were observed shortly after treatment and included lethargy, piloerection, ataxia and increased salivation. These signs were accompanied by increased respiratory rate in rats treated at 100mg/kg and decreased respiratory rate in rats treated above 100 mg/kg bw. Mortality was observed within 1 h to 22 h of treatment. Autopsy revealed slight heamorrhage of the lungs, pallor of the spleen, darkening of the liver and injection of peritoneal blood vessels. However, terminal autopsy findings of surviving animals were normal.

The recovery of surviving animals was apparently complete within 5 d of treatment as exhibited by external appearance and behavior. A slight depression in body weight gain during first week was observed in female rats treated with 64 and 100 mg/kg bw and all surviving male rats. However, bodyweight gain returned to normal during second week.

The acute median oral LD50 of Toluene-2, 5-diamine in 0.05% aqueous sodium sulphite vehicle was found to be 102 mg/kg bw (95% CI= 69-150 mg/kg bw).