Reaction mass of bis[3-[[4-[benzylmethylamino]phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium] tetrachlorozincate(2-) and bis[5-[[4-[benzylmethylamino]phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium] tetrachlorozincate(2-)

Endpoint summary

Description of key information

The LD50 (oral, gavage) of the test substance to male/female rats is 934 mg/kg bw corresponding to 560 mg/kg bw based on active ingredient. The substance is classified as Category 4.

In an acute dermal toxicity study in rabbits, no adverse effects were observed. The dermal LD50 is above 2000 mg/kg bw.

No study on acute toxicity via inhalation was conducted to an unlikely exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: DR. K. THOMAE GMBH
- Weight at study initiation:
males (161- 178) g
females (172 - 181) g
- Fasting period before study: the animals are given no feed 16 hours before administration, but water is available ad libitum.
- Housing: 5 rat housing in a stainless steel wire mesh cages, type DK-III
- Diet: kliba-labordiaet. fa. klingentalmuehle ag ch-4303 ka i seraugst, switzerland.ad libitum
- Water: tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): fully air-conditioned room by central air-conditioning system
- Photoperiod (hrs dark / hrs light): 12 hours cycle dark/light between 6:00 AM to 6:00 PM

Route of administration:

oral: gavage

Vehicle:

physiological saline

Details on oral exposure:

Form of administration: suspension

Amounts administered:
- Dose (mg/kg) 1210 825 562
- Conc. (w/v) 12.10 8.25 5.62
- Adm. vol. (ml/kg) 10 10 10

Doses:

562, 825, 1210 mg/kg bw

No. of animals per sex per dose:

5 per sex per doses

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14
- Frequency of observations and weighing: recording of signs and symptoms several times on the day of administration, at least once each workday. check for moribund and dead animals twice each workday and once on holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: gross-pathological examination

Statistics:

The slope factor was calculated by probit analysis, cambridge university press, 3rd ed., 1971

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 934 mg/kg bw

Based on:

test mat.

95% CL:

> 785 - < 1 145

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 560.4 mg/kg bw

Based on:

act. ingr.

Mortality:

yes

Clinical signs:

other: dyspnoea, apathy, staggering, urine red, salivation, poor general state

Gross pathology:

snout, paws and mucosa of stomach discolored by the test substance

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 (oral, gavage) of the test substance to male/female rats is 934 mg/kg bw corresponding to 560 mg/kg bw based on active ingredient. The substance is classified as Category 4.

Executive summary:

The substance has been tested for acute toxicity by oral route. The substance was administered by gavage at nominal concentrations of 562, 825 and 1210 mg/kg bw to 5 females and 5 males rats. Signs and symptoms are registered several times on the day of administration and at least once each workday. The check for moribund and dead animals was registered twice each workday and once on holidays. Under the test conditions the substance couse dyspnoea, apathy, staggering, urine red, salivation and poor general state. The autopsy reveals snout, paws and mucosa of stomach discolored by the test substance. The LD50 of the test substance is 934 mg/kg b.w. corresponding to 560.4 mg/kg b.w based on active ingredient.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

934 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

1977/78

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: 16 CFR Part 1500 - HAZARDOUS SUBSTANCES AND ARTICLES; ADMINISTRATION AND ENFORCEMENT REGULATIONS

Deviations:

no

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: local supplier
- Age at study initiation: 8 to 11 weeks
- Housing: 1/cage in suspended wire mesh cages (30" x 1.8" x 18") in temperature controlled rooms
- Diet (e.g. ad libitum): Purina Rabbit Chow ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 7 days

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure:200 square cm
- % coverage : 10% of the body surface.
- Type of wrap if used: gauze patches and impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The exposure site was washed with warm tap water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/kg bw


Twenty-four hours prior to dosing the backs of the rabbits were clipped free of fur with an Oster ANG-RA clipper head designed specifically for clipping rabbits. The rabbits were returned to their cages overnight. Just prior to dosing one half of the rabbits were abraded with a 21 gauge bent tip needle. The abrasions, made every 2 to 3 cm longitudinally, scratched the stratum corneum, but did not disturb the derma or produce bleeding.
The test material was applied to the backs of two male and two female rabbits at a dose of 2.0 g/kg. The test site was covered with gauze and the trunk was wrapped with impervious material for 24 hours. Following removal of the binder at 24 hours, the test site was washed with warm tap water. One hour after washing the test sites were graded for skin irritation according to the attached scale. Skin sites were read again at 7 and 14 days. Body weights were recorded pretest and at 7 and 14 days. The rabbits were observed daily for 14 days for signs of toxicity or mortality. Necropsies were performed on all rabbits.

Duration of exposure:

The test material was kept in contact with the skin for 24 hours, at which time the wrappings were removed.

Doses:

2.0 g/kg bw

No. of animals per sex per dose:

2

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weigthing: Dermal reactions were scored at 25 hours, 7 and 14 days by the Draize scoring system. The rabbits were observed daily for 14 days for signs of toxicity, pharmcaological effects and mortality. Body weights were recorded pretest and in the survivors at 7 and 14 days.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

0/2 male
0/2 female

Clinical signs:

other: no systemic or local effects

Gross pathology:

Liver purple: 1/4
Lungs purple: 2/4
Kidney Mottled: 2/4

Interpretation of results:

other: no dermal toxicity observed

Conclusions:

The test material is not toxic , as defined in 16 CFR 1500.3, at a dose level of 2.0 g/kg of body weight.

Executive summary:

2 males and 2 females New Zealand White rabbits were dosed at 2.0 g/kg of body weight. The substance was prepared at 50% w/v in distilled water. The test material was applied once dermally to the prepared site under gauze patche and was kept in contact with the skin for 24 hours. The exposure site was washed with warm tap water to remove excess material.

The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pretest and in the survivors at 7 and 14 days. Animals were generally healthy throughout the 14 day test period. No erythema or edema were observed either on intact or abraded skin during the 14 days observation period. Necropsies of animals sacrificed on Day 14 revealed purple liver and lungs in one or two rabbits, respectively and mottled kidneys in two rabbits. There were no other abnormalities.

In conclusion, all animals survived this test at 2.0 g/kg of body weight and the test material is considered not toxic at this dose level.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The substance has been tested for acute toxicity by oral route. The substance was administered by gavage at nominal concentrations of 562, 825 and 1210 mg/kg bw to 5 females and 5 males rats. Signs and symptoms are registered several times on the day of administration and at least once each workday. The check for moribund and dead animals was registered twice each workday and once on holidays. Under the test conditions the substance couse dyspnoea, apathy, staggering, urine red, salivation and poor general state. The autopsy reveals snout, paws and mucosa of stomach discolored by the test substance. The LD50 of the test substance is 934 mg/kg b.w. corresponding to 560.4 mg/kg b.w based on active ingredient.

Acute dermal toxicity was investigated in 2 males and 2 females New Zealand White rabbits at a single dose level 2000 mg/kg of body weight. The substance was prepared at 50% w/v in distilled water. The test material was applied once dermally to both, intact and abraded skin for 24 hours. The exposure site was washed with warm tap water to remove excess material.

The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pretest and in the survivors at 7 and 14 days. Animals were generally healthy throughout the 14 day test period. No erythema or edema were observed either on intact or abraded skin during the 14 days observation period. Necropsies of animals sacrificed on Day 14 revealed purple liver and lungs in one or two rabbits, respectively and mottled kidneys in two rabbits. There were no other abnormalities.

In conclusion, all animals survived this test at 2000 mg/kg of body weight and the test material is considered not toxic at this dose level.

Justification for classification or non-classification

GHS Category 4 - H302