Registration Dossier

Administrative data

Description of key information

Acute oral toxicity in the rat, OECD 420: LD50oral > 2000 mg/kg bw

Acute dermal toxicty in the rat, OECD 402: LD50 > 2000 mg/kg bw

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:
2016-08-30 - 2016-10-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate issued by the "Department of Health of the Government of the United Kingdom on 2016-10-28.
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 180 to 193g
- Fasting period before study: overnight fast immediately before dosing and for approximately 3-4 hours after dosing.
- Housing: Animals were housed in groups of up to 4 in suspended solid-floor polypropylene cages furnished with woodflakes. Environmental Enrichment Items whoch were considered not to contain any contaminant of a level that might have affected the purpose or integrety of the study are provided.
- Diet: ad libitum (2014C Teklad Global Rodent diet)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 changes / hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential leaving sufficient time to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2 and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily at working days and once daily at weekends and public holidays.
Body Weight was recorded on day 0, day 7 and on day 14.
All animals were subject to gross necropsy which consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Using mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.
Preliminary study:
Not reported. Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study period.
Clinical signs:
No signs of systematic toxicity were noted during the observation period.
Body weight:
All animals gaines body weight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
other: EU GHS (CLP) criteria not met
Conclusions:
An acute oral median LD50 of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.
Executive summary:

A study on acute oral toxicity in the rat has been conducted with the test item according to OECD Guideline 420 and in compliance with GLP criteria. Five female rats (nulliparous and non-pregnant) of the Wistar strain with an initial body weight of 180 to 193g were used as test animals. The rats were deprived of food during the night immediately before dosing and for approximately 3-4 hours after dosing. The test item was injected into each animal by a gavage whereby the dose was 2000 mg / kg body weight. No rats were used as a control group. The observation period was 14 days and ended with the euthanization of the rats on day 14. Clinical observations were made 30 minutes, 1, 2 and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily at working days and once daily at weekends and public holidays. There were no deaths during the study period and no signs of systematic toxicity were noted during the observation period. Body weight was recorded on day 0, day 7 and on day 14: all animals gained body weight during the study period. The mean body weight of the 5 test animals was 185.6 g at day 1 and increased to 224 g at day 14. Each animal was subject to gross necropsy which consisted of an external examination and opening of the abdominal and thoracic cavities. No abnormalities were noted at necropsy.

An acute oral median LD50 of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Good quality due to well documented guideline study.

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:
2016-09-20 - 2016-10-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate issued by "The Department of Health of the Government of the United Kindom" (2016-10-28).
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMs (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: at least 200g, the weight variation did not exceed ± 20% of the mean weight for each sex.
- Housing: The animals were housed idividually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 -70%
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: shorn skin on back and flanks of each animal
- % coverage: approximately 10% of total body surface area
- Type of wrap if used: self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, wiped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Dose level: 2000 mg/kg
- Dose volume: 1.8 mL/kg

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations 30 minutes, 1, 2 and 4 hours after exposure. On the subsequent days once daily. Weighing of the individuals occured on day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: skin reactions observed daily, body weight (day 0, 7 and 14), toxicological effects, behavioural and clinical abnormalities.
Statistics:
Not reported. Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.
Preliminary study:
Not performed. Use of available information on the toxicity of the test item to determine the dose.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
Animals showed expected gain in body weight over the study period, except for two females which showed body weight loss or no gain in body weight during the first week but expected gain of body weight during the second week
Gross pathology:
Very slight erythema (barely perceptible) was observed at the test sites of all animals 1 day after dosing and persisted in one male and two females 2 days after dosing.
Interpretation of results:
other: EU GHS (CLP) criteria not met
Conclusions:
No mortality occurred at a maximum tested level of 2000 mg/kg bw and the study has been completed as a limit test. The LD50 is considered to be more than 2000 mg/kg.
Executive summary:

An acute dermal toxicity study was conducted according to OECD Guideline 402 and in compliance with GLP criteria. The initial weight of each of 5 Wistar strain rats per sex was at least 200 g. Approximately 24 hours prior to the application of the test material, the hair of each animal was closely clipped on the back and the flanks. A single dose of 2 g/kg of the test material was administered dermally to five male and female animals. The test material was kept in contact with the skin for a period of 24 consecutive hours under a self-adhesive bandage. The application site and surrounding areas were wiped clean of residual test material at the end of the 24-hour exposure period with cotton wool moistened with distilled water. The animals were observed for abnormal clinical and behavioral signs frequently on the day of dosing and once daily for 14 days after treatment. Individual body weights were recorded on the day of dosing and on days 7 and 14. No rats were used as a control group. The observation period was 14 days and ended with the euthanization of the rats on day 14. Body weight was recorded on day 0, day 7 and on day 14: animals showed expected gain in body weight over the study period, except for two females which showed body weight loss or no gain in body weight during the first week but expected gain of body weight during the second week. Each animal was subject to gross necropsy which consisted of an external examination and opening of the abdominal and thoracic cavities. Very slight erythema (barely perceptible) was observed at the test sites of all animals 1 day after dosing and persisted in one male and two females 2 days after dosing. There were no deaths during the study period and no signs of systemic toxicity were noted during the observation period. An acute dermal median LD50of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Good quality due to well documented guideline study.

Additional information

Acute oral toxicity

The key study on acute oral toxicity in the rat (Sanders, 2017) has been conducted with the test item according to OECD Guideline 420 and in compliance with GLP criteria. Five female rats (nulliparous and non-pregnant) of the Wistar strain with an initial body weight of 180 to 193g were used as test animals. The rats were deprived of food during the night immediately before dosing and for approximately 3-4 hours after dosing. The test item was injected into each animal by a gavage whereby the dose was 2000 mg/kg body weight. No rats were used as a control group. The observation period was 14 days and ended with the euthanization of the rats on day 14. Clinical observations were made 30 minutes, 1, 2 and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily at working days and once daily at weekends and public holidays. There were no deaths during the study period and no signs of systematic toxicity were noted during the observation period. Body weight was recorded on day 0, day 7 and on day 14: all animals gained body weight during the study period. The mean body weight of the 5 test animals was 185.6 g at day 1 and increased to 224 g at day 14. Each animal was subject to gross necropsy which consisted of an external examination and opening of the abdominal and thoracic cavities. No abnormalities were noted at necropsy.

An acute oral median LD50 of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Acute dermal toxicity

An acute dermal toxicity key study (Sanders, 2016) was conducted according to OECD Guideline 402 and in compliance with GLP criteria. The initial weight of each of 5 Wistar strain rats per sex was at least 200 g. Approximately 24 hours prior to the application of the test material, the hair of each animal was closely clipped on the back and the flanks. A single dose of 2 g/kg of the test material was administered dermally to five male and female animals. The test material was kept in contact with the skin for a period of 24 consecutive hours under a self-adhesive bandage. The application site and surrounding areas were wiped clean of residual test material at the end of the 24-hour exposure period with cotton wool moistened with distilled water. The animals were observed for abnormal clinical and behavioral signs frequently on the day of dosing and once daily for 14 days after treatment. Individual body weights were recorded on the day of dosing and on days 7 and 14. No rats were used as a control group. The observation period was 14 days and ended with the euthanization of the rats on day 14. Body weight was recorded on day 0, day 7 and on day 14: animals showed expected gain in body weight over the study period, except for two females which showed body weight loss or no gain in body weight during the first week but expected gain of body weight during the second week. Each animal was subject to gross necropsy which consisted of an external examination and opening of the abdominal and thoracic cavities. Very slight erythema (barely perceptible) was observed at the test sites of all animals 1 day after dosing and persisted in one male and two females 2 days after dosing. There were no deaths during the study period and no signs of systemic toxicity were noted during the observation period. An acute dermal median LD50 of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Acute inhalation toxicity

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 the possibility of exposure to aerosols, particles or droplets of an inhalable size. Due to the low volatility (vapour pressure of 0.04 Pa at 25°C) the registered substance is unlikely to be available for inhalation as a vapour. In addition, as the substance is a liquid, no inhalable particles occur. Thus, it is very unlikely that considerable amounts of the substance reach the lung.

Justification for classification or non-classification

The test item had an acute oral and dermal LD50 of > 2000 mg/kg bw. The test item does not bear a risk by the inhalative route of exposure, due to its low vapour pressure and exposure considerations.

Therefore the magnesium metaborate test item does not meet the criteria for classification and labelling for oral, dermal or inhalation toxicity in accordance with Regulation (EC) No 1272/2008 (CLP Regulation).