1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates

Endpoint summary

Description of key information

LD50, oral, rat (m/f) ca. 3800 mg/kg bw /day (BASF, 1979)
LD50, dermal, rat, (m/f) > 1000 mg/kg bw /day (BASF, 1979)
LC50, inhalation, rat (m/f) > 5610 mg/m3 (BASF, 1978)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

08. Feb. 1978 - 17. Mar. 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline studies with acceptable restrictions performed on analogue substance 1

Principles of method if other than guideline:

BASF-Test. In principle, the methods described in OECD Guideline 401 were used.5 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in water. Group-wise documentation of clinical signs was performed over the 7 day study period. The clinical signs and findings were reported in summary form. On the basis of the observed lethality, the LD50 value was estimated or determined using a graphical evaluation of the dose response curve on probability paper.

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Weight at study initiation: male: 210 (mean), female: 160 (mean)

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE- Concentration in vehicle: 5000 mg/kg: 50%3160 mg/kg: 31.6%2150 mg/kg: 21.5%1470 mg/kg: 14.7%

Doses:

5000mg/kg, 3160 mg/kg, 2150 mg/kg, 1470 mg/kg

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 14 days - Frequency of observations: daily- Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 3 800 mg/kg bw

Mortality:

5000 mg/kg: 1 male and 1 female died within 5 days, 1 male and 3 females died within 6 days and 1 male and 1 female died on day 7.3160 mg/kg: 1 male died within day 3 and 1 within day 6. 1 female died on day 7.2150 mg/kg: No mortality was observed.1470 mg/kg: 1 female died within 4 days.

Clinical signs:

other: Poor general state in the 1st week of the study. Occurrence of death and loss of weight at the end of the 1st week of the study. 5000 mg/kg: Immediately after the application: apathy, irregular respiration, tumbling, spastic gait, discoloured urine (orang

Gross pathology:

Animals that died spontaneously:5000 mg/kg: Animals that died within 2 days: Heart: acute dilatation on the right; acute congestive hyperemia; adipose tissue/muscles: stained brown-yellow; intestine: single cases of a state indicative of preceding diarrhea. Animals that died within 4 days: intestine: dark brown contents; liver, kidneys, heart and lung: dark complexion, peritoneum and subcutis: stained brown-yellow. Animals that died within 6 days: cadaverous, probably overstaining of organs.3160 mg/kg: animals that died within 3 days: Heart: acute dilatation on the right; acute congestive hyperemia; adipose tissue/muscles: stained orange; animals that died within 6 days: conspicuously grey musculature; lung: wet, fleshy, hyperemia; liver: despite blood-filled conspicuous centrilobular pattern visible. Animals that died within 7 days: heart: dilatation of the ventricle; congestive hyperemia; muscles: despite cadaverous conditions grey-yellow staining observable.Sacrificed animals:5000 mg/kg: Kidneys: conspicuously dark.3160, 2150 and 1470 mg/kg: No abnormalities were observed.

Mortality:

Dose: mg/kg	gender	1h	24h	48h	7 days	14 days
5000	Male	0/5	0/5	0/5	3/5	3/5
5000	Female	0/5	0/5	0/5	5/5	5/5
3160	Male	0/5	0/5	0/5	2/5	2/5
3160	Female	0/5	0/5	0/5	1/5	1/5
2150	Male	0/5	0/5	0/5	0/5	0/5
2150	Female	0/5	0/5	0/5	0/5	0/5
1470	Male	0/5	0/5	0/5	0/5	0/5
1470	Female	0/5	0/5	0/5	1/5	1/5

Weight in g (mean):

Dose: mg/kg	gender	0 days	2 days	7 days	13 days
5000	Male	210	215	180	228
5000	Female	160	162	-	-
3160	Male	210	218	184	249
3160	Female	180	180	162	208
2150	Male	210	208	234	268
2150	Female	180	173	185	217
1470	Male	170	195	216	253
1470	Female	180	176	191	213

Interpretation of results:

practically nontoxic

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The analogue substance 1 was tested for acute toxicity oral rats following a method similar to OECD401. Under the experimental conditions the substance showed LC50 ca 3800 mg/kg bw /day.

Executive summary:

The analogue substance 1 was tested for acute toxicity oral rats following a method similar to OECD401. The doses were 5000, 3160, 2150 and 1470 mg/kg bw /day by gavage for 5 animals/dose. Under the experimental conditions the substance showed LC50 ca 3800 mg/kg bw /day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 800 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

other: read across from analogue substance

Adequacy of study:

key study

Study period:

19. Apr 1978 - 05. May 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline studies with acceptable restrictions performed on analogue substance 1

Principles of method if other than guideline:

Inhalation Hazard Test: The test was performed equivalent or similar to the method described in H.F. Smyth et. al. Am. Ind. Hyg. Ass. 23, 95-107 (1962). Inhalation of an atmosphere enriched at room temperature with the dust of the test material by rats for 7 hours. The documentation of clinical signs was performed over a period of 7 days.

GLP compliance:

no

Test type:

other: Inhalation hazard test.

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Weight at study initiation: male: 185 g (mean), female: 221 g (mean)

Route of administration:

inhalation: dust

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION- pressure in air chamber: 1.013 bar

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

ca. 7 h

Concentrations:

7.91 mg/l (nominal)

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days - Frequency of observations: daily- Necropsy of survivors performed: yes- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.61 mg/L air

Based on:

act. ingr.

Exp. duration:

7 h

Mortality:

No mortality was observed.

Clinical signs:

other: 7 h post exposure occured irregular respiration, bloody nose discharge and scrubby fur. 6 days post exposure all animals were considered as normal.

Gross pathology:

No abnormalities were observed.

Interpretation of results:

practically nontoxic

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Analogue substance 1 was tested for inhalation toxicity on rat exposed to dust in a concentration of 5.61 mg/l of active ingredient for 7 hours. The animals of both sex have been observed for 7 days after exposure and the effects reported. No mortality was observed at the concentration of 5.61 mg/l.

Executive summary:

Analogue substance 1 was tested for inhalation toxicity on rat exposed to dust in a concentration of 5.61 mg/l of active ingredient for 7 hours. The animals of both sex have been observed for 7 days after exposure and the effects reported. No mortality was observed at the concentration of 5.61 mg/l.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 610 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17. Apr 1974 - 02. May 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles

Principles of method if other than guideline:

BASF-Test. The study was performed according to: Noakes D.N. and Sanderson D.M., A Method for Determining the Dermal Toxicity of Pesticides. Brit. Journ. Ind. Med. 26, 59, 1969. 5 animals were treated for 4 or 24 h using occlusive conditions. An application site of 50 cm² was covered with the test substance and the trunk of the rat was encircled with a strip of plaster (2 layers). After the exposure time the skin was washed with detergent and water. The animals were observed 8 days and skin changes were recorded daily.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: WIGA- Weight at study initiation: male: 144g (mean); female: 134g (mean)

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE- Area of exposure: 50 cm²REMOVAL OF TEST SUBSTANCE- Washing: After the exposure time the skin was washed with detergent and water.TEST MATERIAL- Concentration (if solution): 100%- Constant concentration used: yes

Doses:

5 ml/kg (equivalent to 5g/kg)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days - Frequency of observations and weighing: Animals were weighted prior to exposure and symptoms were recorded daily.- Necropsy of survivors performed: yes- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: see overall remarks.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality was observed.

Clinical signs:

other: No abnormal clinical signs could be observed. All animals obtained local staining (brown) from residual substance.

Gross pathology:

No abnormalities were noted at necropsy.

Mortality:

Dose:	sex:	1h	24h	48h	7 days	14 days
5  ml/kg	male	0/5	0/5	0/5	0/5	0/5
5 ml/kg	female	0/5	0/5	0/5	0/5	0/5

Interpretation of results:

practically nontoxic

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The substance was tested for acute toxicity dermal in rats following Noakes D.N. and Sanderson D.M., A Method for Determining the Dermal Toxicity of Pesticides. Brit. Journ. Ind. Med. 26, 59, 1969. Under the experimental conditions the substance has LD50 > 1000 mg/kg bw /day (> 5000 mg/kg bw/day for the mixture preparation).

Executive summary:

The substance was tested for acute toxicity dermal in rats following Noakes D.N. and Sanderson D.M., A Method for Determining the Dermal Toxicity of Pesticides Brit. Journ. Ind. Med. 26, 59, 1969.One single dose of 5000 mg/kg bw /day was tested on 5 rats (male and female) by occlusive application. Under the experimental conditions the substance has LD50 > 1000 mg/kg bw /day (> 5000 mg/kg bw/day for the mixture preparation).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Additional information

Valid in vivo data are available for the assessment of the acute toxicity of the test substance.

Oral and inhalation exposure patterns are covered by two studies on analogue substance 1 while dermal toxicity is assessed through a study on the substance itself.

Mortality was observed at the highest dose used in the oral test (i.e. 3800 mg/kg bw /day) after one week and it was not observed at the concentration of the inhalative test (LC50 (LC0)> 5610 mg/m3). For dermal exposure the recalculated LD50 is > 1000 mg/kg bw /day but no mortality was observed for the whole period of observation (LD0). Moreover, the substance which is polar is unlikely to be absorbed by the skin barrier and be systemically present.

Based on the read across considerations and the testing results, Basic Brown 1 acetate is not considered toxic after single acute dermal, oral or inhalative exposure.

Justification for selection of acute toxicity – oral endpoint
The test with guidelines similar to OECD401 performed on rats was chosen for classification and hazard assessment

Justification for classification or non-classification

Based on the results of acute oral, inhalative and dermal toxicity, no classification for acute toxicity is warranted under Regulation 1272/2008