Bromo(hexahydro-2H-azepin-2-onato-N)magnesium

Endpoint summary

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:

01/2008 to 03/2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 07072601
- Expiration date of the lot/batch: 26.07.2008

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle - France)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 189 to 209 g
- Fasting period before study: yes
- Housing: solid-bottomed clear polycarbonate cages with a stainless steel mesh lid
- Water (e.g. ad libitum): tap-water from public distribution system
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22
- Humidity (%): 36 to 57
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg body weight

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: D2, D7, and D14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

not observed

Clinical signs:

It was registered in the treated animals, from thirty minutes after the test item administration, a decrease of the spontaneous activity (6/6) associated with a decrease of the righting reflex (4/6) and a piloerection (6/6). 48 hours after the test item administration, no clinical signs related to the test item administration were noted.

Body weight:

It was noted an absence of the body weight gain in the treated animals, 48 hours after the test item administration. Then the body weight evolution of the animals remained normal throughout the study.

Gross pathology:

The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item Bromo(hexahydro-2H-azepin-2-onato-N)magnesium is higher than 2000 mg/kg body weight by oral route in the rat, in accordance with the OECD guideline n°423.
A classification according to (EU) No. 1272/2008 is not required based on this data.

Executive summary:

The LD50 of the test item Bromo(hexahydro-2H-azepin-2-onato-N)magnesium is higher than 2000 mg/kg body weight by oral route in the rat, in accordance with the OECD guideline n°423.

A classification according to (EU) No. 1272/2008 is not required based on this data.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

satisfying

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

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

Endpoint conclusion:

no study available

Dose descriptor:

LC50

Value:

1 500 mg/m³

Quality of whole database:

Acceptable.
The LC50 is estimated from the lowest LC50 of epsilon-Caprolactam resulting in an ATE =1.5.

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:

02/2008 to 05/2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 07072601
- Expiration date of the lot/batch: 26.07.2008

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

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

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle - France)
- Females (if applicable) nulliparous and non-pregnant: no
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 213 g to 238 g (males) and 203 g to 221 g (females)
- Housing: solid-bottomed clear polycarbonate cages with a stainless steel mesh lid; during the treatment, the animals were kept in an individual cage. At day 3, the animals were put into their cage by 2 or 3
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C to 22°C
- Humidity (%): 34 % to 52 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

water

Duration of exposure:

24 hours

Doses:

2.000 mg/kg bw

No. of animals per sex per dose:

5 male
5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing on day 2, 7 and 14.
- 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:

not observed

Clinical signs:

none

Body weight:

normal weight evolution

Gross pathology:

no reveal treatment-related changes

Neither cutaneous reactions nor systemic clinical signs related to the administration of the test item were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

No need for classificaton as "acute Tox." according to (EU) No. 1272/2008.

Executive summary:

The LD50 of the test item Bromo(hexahydro-2H-azepin-2-onato-N)magnesium is higher than 2,000 mg/kg body weight by dermal route in the rat.

No signs for skin corrosion or irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

satisfying

Justification for classification or non-classification

Oral route:

Bromo(hexahydro-2H-azepin-2-onato-N)magnesium is not classified into the hazard category "Acute Tox, oral", due to an LD50(oral) > 2000 mg/kg bw.

Dermal route:

Bromo(hexahydro-2H-azepin-2 -onato-N)magnesium is not classified into the hazard category "Acute Tox, dermal", due to an LD50(oral) > 2000 mg/kg bw.

Inhalative route:

A test on the inhalative toxicity of Bromo(hexahydro-2H-azepin-2 -onato-N)magnesium is not available. However, the substance hydrolyses under physiological conditions with the formation of epsilon-Caprolactam and basic magnesium bromide. Therefore also the effects of epsilon-caprolactame have to be taken into consideration. Epsilon-caprolactame is harmonised classified into "Acute Tox, inhalativ", category 4, H332, which corresponds to an ATE value of 1.5 mg/l (dust). Thus, Bromo(hexahydro-2H-azepin-2 -onato-N)magnesium is classified into the hazard category "Acute Tox, inhalative", category 4, due to the presence of up to 80% epsilon-caprolactame as a stabiliser. As an estimation, the

ATE value of Bromo(hexahydro-2H-azepin-2 -onato-N)magnesium is considered to have the same value as epsilon-Caprolactam.