N,N,N',N'-tetrakis(2,3-epoxypropyl)-m-xylene-α,α'-diamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

method of administration unclearly defined: using a metal

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

1

Reference substance name:

N,N,N',N'-tetrakis(2,3-epoxypropyl)-m-xylene-α,α'-diamine

EC Number:

264-438-6

EC Name:

N,N,N',N'-tetrakis(2,3-epoxypropyl)-m-xylene-α,α'-diamine

Cas Number:

63738-22-7

Molecular formula:

C20H28N2O4

IUPAC Name:

N,N,N',N'-tetrakis(2,3-epoxypropyl)-m-xylene-α,α'-diamine

Specific details on test material used for the study:

Lot: V-156
Expected purity: 75%
Appearance: light yellow highly viscous liquefied substance

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Laboratory Animals.
- Age at study initiation: 4 weeks upon arrival
- Weight at study initiation: 99 ± 3.3g (male) and 83 ± 2.5g (female)
- Fasting period before study: One night prior to the test. Feeding was resumed three hours after administration.
- Housing: Ten animals were housed in a cage
- Diet: ample food
- Water: ample water
- Acclimation period: Tamed under breeding circumstances for one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2.0 C
- Humidity (%): 45 to 85

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
1.170 mL/ kg and 0.988 mL/ kg of undiluted substance for male and female animals, respectively.

Doses:

Males: 0.392, 0.485, 0.606, 0.714, 0.825, 0.918 and 1.170 mL/ kg bw
Females: 0.349, 0.471, 0.588, 0.741, 0.864 and 0.988 mL/ kg bw

No. of animals per sex per dose:

10

Control animals:

yes

Remarks:

no administration

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight was recorded at 0, 1, 3, 5, 8, 11 and 14 days after exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight are recorded.

Statistics:

LD50 values are calculated according to the Probit method.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

630 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Corresponding to a dose level of 0.55 mL/kg bw

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

730 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Corresponding to a dose level of 0.63 mL/kg bw

Mortality:

1/10, 5/10, 3/10, 5/10, 6/10, 9/10 and 10/10 males died in observation period after exposure period to 0.392, 0.485, 0.606, 0.714, 0.825, 0.918 and 1.170 mL/ kg bw, respectively.
0/10, 5/10, 7/10, 6/10, 8/10 and 10/10 females died in the observation period after exposure period to 0.349, 0.471, 5.88, 0.741, 0.864 and 0.988 mL/ kg bw, respectively.

The mortalities occurred on day 4 to 8 of the 14-day observation period. No deaths occurred in the control group.

Clinical signs:

other: No toxic symptoms were noted for 2 days after administration, but severe diarrhoea, reddish brown vomit or lacrimation, decline of spontaneous movement and blephroptosis were suddenly observed on and after the third day after administration in the order o

Gross pathology:

As to rats that died during the test, ulceration or necrosis was observed in the stomach and intestinal canal. Such symptoms in the stomach were particularly pronounced. No remarkable change was observed in other organs. As to rats that lived for 14 days, the accretion of the stomach (mainly anteriorly) with thoracie peritoneum was observed in the male group with a tendency to increasing accretion at higher doses. No extreme change was observed in the female group.

Any other information on results incl. tables

Calculation of LD50 value according to Probit method.

Male: 0.63 mL/kg (0.53-0.73 mL/kg, p=0.05) = 730 mg/kg (610-840 mg/kg, p= 0.05)

Female: 0.55 mL/kg (0.45-0.64 mL/kg, p=0.05) = 630 mg/kg (520- 730 mg/kg, p=0.05)

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral toxicity test showed a LD50 of 630 and 730 mg/kg bw for female and male rats, respectively.

Executive summary:

A pre-guideline study, similar to OECD guideline 401, was performed to identify the acute oral toxicity of the test substance. Although the details on administration are not very clearly described, it is clear that the substance was administered by gavage. In this study 10 conventional Wistar rats were used per sex and per dose group, which were observed for 14 days post administration. In the males, administration of 0.392, 0.485, 0.606, 0.714, 0.825, 0.918 and 1.170 mL/ kg bw resulted in mortality in 1/10, 5/10, 3/10, 5/10, 6/10, 9/10 and 10/10 of the animals, respectively. For females exposed to 0.349, 0.471, 5.88, 0.741, 0.864 and 0.988 mL/ kg bw mortality was observed in 0/10, 5/10, 7/10, 6/10, 8/10 and 10/10 of the animals, respectively. No mortality was observed in the control (untreated) group. The Probit method was used to calculate the LD50 values, which were determined to be 630 mg/kg bw (0.55 mL/kg bw) for females and 730 mg/kg bw (0.63 mL/kg bw) for males.

Clinical signs were noted from day 2 till the end of the observation period and included severe diarrhoea, reddish brown vomit or lacrimation, decline of spontaneous movement and blephroptosis. Rats succumbing during observation exhibited ataxia and oppression in breathing before death. Bodyweight was reduced in a dose dependent manner between day 1 and 5 if compared to the bodyweight at day 0. During the whole observation period, the absolute bodyweight of the treated animals was lower compared to the controls. Necropsy revealed ulceration or necrosis in the stomach and intestinal canal of the rats that died during the observation period. In these rats no remarkable change was observed in other organs. As to rats that lived for 14 days, the accretion of the stomach (mainly anteriorly) with thoracie peritoneum was observed in the male group with a tendency to increasing accretion at higher doses. No extreme change was observed in the female group. Based on the LD50 values obtained, the substance is considered to be acutely harmful Category 4.