Copper, diammine[5,5'-bi-1H-tetrazolato(2-)-kN1, kN1']

Endpoint summary

Description of key information

According to acute oral toxicity assay, copper Diammine Bitetrazole (CuDABT) is considered as non-toxic or in UN GHS No category (LD50 > 2,000 mg/kg). No hazard statement or signalling is required.

Inhalation acute toxicity assay is not necessary because of the high particle size and very low vapor pressure.

Dermal acute toxicity assay is not necessary because no adverse effect was observed in the acute toxicity assay by oral route and the skin sensitization in vivo study shows no systemic effect.

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:

June to July 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

study performed in accordance with guideline OECD423 and GLP. CuDABT concentration are only followed by total copper analysis. Preliminary analysis shows that total copper represents CuDABT appropriately. Some minor deviations as aslo observed but conidered have no significant impact on the result and the validity of the study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

CuDABT concentration are only followed by total copper analysis (this represents CuDABT appropriately). Some minor deviations as aslo observed but conidered have no significant impact on the result and the validity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Provider : AUTOLIV ASP, 16700 W. Hwy 83, Promontory, UTAH 84307, USA
- batch No. P3656461
- Expiration date of the lot/batch: august 25th 2020
- Purity: 97.4%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in a restricted area dedicated to explosive products, at outside temperature and humidity
- Solubility and stability of the test substance in the solvent/vehicle: not soluble in water, homogeneous suspensions in water

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: no treatment

FORM AS APPLIED IN THE TEST (if different from that of starting material)
homogeneous suspensions in water

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier LABS, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10 weeks
- Weight at study initiation: 195-240 g
- Fasting period before study: approximately 5:00 pm on day before treatment to 3 hours after treatment
- Housing: polycarbonate cages (Makrolon type III high) containing autoclaved dust-free bedding
- Diet ad libitum
- Water; filtered tap water ad libitum
- Acclimation period: 5, 7, 12 or 14 days depending of group

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): 15 to 20 cycles/hour of filtered, non recycled air
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: june 14th 2016 To: july 7th 2016

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 g/L (for 300 mg/kg dose) and 200 g/l (for 2000 mg/kg dose)
- Amount of vehicle (if gavage): 10 mL/kg of body weight
- Justification for choice of vehicle: drinking water


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg of body weight

DOSAGE PREPARATION (if unusual): homogeneous suspension

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the initial dose of 300 mg/kg BW was chosen according to OECD No. 423 guideline

Doses:

300 mg/kg BW
2000 mg/kg BW

No. of animals per sex per dose:

6 females rats per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily, several times on the day of treatment
- Frequency of weighing: day of arrival, day before treatment, daily from D0 to D14
- Necropsy of survivors performed: yes
- Examinations performed: clinical signs, body weight, macroscopic observation of organs of thoracic area and of abdominal area

Statistics:

no statistic

Preliminary study:

Suspensions of CuDABT in Milli-Q water, at 30 g/L and at 200 g/L, were homogeneous at initial time and 7 days after preparation, and stable 5 hours and 7 days after preparation.
Dissolved copper was assessed to evaluate potential dissociation of CuDABT in both copper and 5,5’-bi-1H-tetrazole diammonium. Dissolved copper measurements in suspension indicated that there was very little dissolved copper (max 0.03% at initial time). Dissolved copper concentration was lower at 7 days than at initial time. Therefore, a fresh CuDABT suspension was prepared the morning of each administration day.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

not determinable

Mortality:

No unscheduled deaths were observed on rats treated with the test item at 300 mg/kg and at 2000 mg/kg during the observation period.

Clinical signs:

No clinical signs of toxicity were observed on rats in the 300 mg/kg group, during the observation period. Nose irritation red (rat 419) were observed in the 300 mg/kg group. These clinical signs were not considered to be related to test item administration.
No clinical signs of toxicity were observed on rats in the 2000 mg/kg group, during the observation period. Wound, scabs (rat 425) were observed in the 2000 mg/kg group. These clinical signs were not considered to be related to test item administration.

Body weight:

At reception, 8 week-old rats had a higher body weight than 9 week-old rats. Therefore, a weight difference at D0 was observed between group 1 and group 2 rats. This difference remained stable throughout the in-life observation period. The body weight gain was the similar for all animals.

Gross pathology:

No macroscopic changes were observed by external examination of the body and in lung with trachea, heart, liver, oesophagus, spleen, pancreas, digestive system, kidneys, adrenal glands, bladder, lymph nodes and reproductive organs.

Interpretation of results:

GHS criteria not met

Conclusions:

In accordance with the EC No. 1272/2008 Regulation, the test item Copper Diammine Bitetrazole (CuDABT) is considered as non-toxic or in UN GHS No category. No hazard statement or signalling is required.

Executive summary:

The goal of this study was to evaluate the acute oral toxicity of the test item Copper Diammine Bitetrazole (CuDABT), in rat. The study design was established in accordance with OECD Guideline No. 423 "Acute Oral Toxicity – Acute Toxic Class Method", December 17th, 2001.

Method

At 30 g/L and 200 g/L, the test item was not soluble in water. In the preliminary assay, suspensions of test item at 30 and 200 g/L were homogenous at initial time and 7 days after preparation. The test item preparations were stable at 5 hours and at 7 days.

Test item suspensions were prepared the day of administration and stirred continuously, in order to obtain and maintain a homogeneous suspension throughout the administration.

For each dose, six nulliparous and non gravid female WISTAR rats were treated with the test item in 2 successive sessions (3 rats per session). The session using the higher dose of the test item was started only when it was certain that the rats treated in the preceding session survived.

For each session, each animal was observed at least once a day for mortality, clinical signs and body weight, during 15 days. On completion of the observation period, all animals were euthanized and a necropsy including macroscopic examination of all major organs was realized.

Results

Test item doses and treatment

Based on the TG423 Guideline, theoretical doses were 300 and 2000 mg/kg. Suspensions used to treat animals were analyzed. Corresponding doses were: 340 ± 5.7 mg/kg and 2136 ± 145 mg/kg.

Mortality and clinical signs:

No unscheduled deaths and no clinical signs of toxicity were observed on rats treated with the test item at the 300 mg/kg dose, during the observation period.

No unscheduled deaths and no clinical signs of toxicity were observed on rats treated with the test item at the 2000 mg/kg dose, during the observation period.

Macroscopic examination

External examination of the body was normal. No macroscopic changes was observed in lung with trachea, heart, liver, oesophagus, spleen, pancreas, digestive system, kidneys, adrenal glands, bladder, lymph nodes and reproductive organs.

Conclusion

In accordance with the EC No. 1272/2008 Regulation, the test item Copper Diammine Bitetrazole (CuDABT) is considered as non-toxic or in UN GHS No category. No hazard statement or signalling is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study technically not feasible

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Quality of whole database:

In accordance with column 2 of REACH Annex VIII (Regulation (EU) 2016/863), testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. Furthermore, the OECD guidance document 436 indicates that to allow for exposure of all relevant regions of the respiratory tract, aerosols with mass median aerodynamic diameters ranging from 1 to 4 µm are recommended. The particle size distribution (section 4.5) of CuDABT shows that only 3 % of particles are below 4 µM and the vapour pressure is very low: 0.0000000127 Pa (section) 4.6. Therefore, acute inhalation toxicity test is not performed.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study need not be conducted because (i) inhalation of the substance is likely and (ii) skin contact in production and/or use is not likely and (iii) the physicochemical and toxicological properties suggest no potential for a significant rate of absorption

Endpoint conclusion

Quality of whole database:

In accordance with column 2 of REACH Annex VIII (Regulation (EU) 2016/863), Testing by the dermal route does not need to be conducted if:
-the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and,
-no systemic effects have been observed in in vivo studies with dermal exposure.
No adverse effect was observed in the acute toxicity assay by oral route (CuDABT is not classified for acute oral toxicity) and the skin sensitization in vivo study shows no systemic effect. Therefore, acute toxicity dermal test is not performed.

Justification for classification or non-classification

In accordance with the EC No. 1272/2008 Regulation, the test item Copper Diammine Bitetrazole (CuDABT) is considered as non-classified or in UN GHS No category. No hazard statement or signaling is required.