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Diss Factsheets

Administrative data

Description of key information

Acute oral toxicity : The oral LD50 in male and female Sprague-Dawley rats was determined to be 5000 mg/kg bw in a reliable, key study conducted similarly to OECD guideline 420 (Calvert Laboratories, Inc., 2010).
Acute inhalation toxicity: No reliable data were available. However, this endpoint is waived for the inhalation route as specific data are available for the oral and dermal route.
Acute dermal toxicity: In a reliable, key study conducted similarly to OECD guideline 402 and EPA OPPTS 870.1200, the acute dermal LD50 was determined to be greater than 2000 mg/kg bw in male and female Sprague-Dawley rats.

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:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): amine C-8
- Substance type: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley or any acceptable USDA source
- Age at study initiation: 8-12 weeks at start of dosing
- Weight at study initiation: Male: 175-300 grams; female: 150-250 grams
- Fasting period before study: 18-24 hours prior to test article administration
- Housing: Animals will be housed (group housed by sex upon receipt, individually housed upon assignment to study) in compliance with the National Research Council "Guide for the Care and Use of Laboratory Animals". Calvert is a USDA registered and fully AAALAC accredited facility. The room in which the animals will be kept will be documented in the study records. No other species will be kept in the same room.
- Diet (e.g. ad libitum): All animals will have access to Harlan Teklad Rodent Diet (certified) or an equivalent certified diet ad libitum. The lot number(s) and specifications of each lot used are archived in the facility records at Calvert. No contaminants are known to be present in the certified diet at levels that would be expected to interfere with the results of this study. Analysis of the diet was limited to that performed by the manufacturer, records of which will be maintained in the Calvert archives.
- Water (e.g. ad libitum): Tap water will be available ad libitum, to each animal via an automatic watering device. The water is routinely analyzed for contaminants as per Calvert's SOPs. No contaminants are known to be present in the water at levels that would be expected to interfere with the results of this study. Results of the water analysis will be maintained in the Calvert archives.
- Acclimation period: Study animals will be acclimated to their housing for a minimum of five days prior to their first day of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 26 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: No data
Route of administration:
oral: gavage
Details on oral exposure:
Prior to the main assay, a dose range finding study (non-GLP) is performed using one male and one female rat per dose level. Three dose levels selected by the Sponsor are administrated to the animals. The procedures follow the main assay, but the length of study is 72 hours. After review of the dose range results, groups of 5 males and 5 females will be added in a step-like manner depending on the results of each previous dose level.
Doses:
1000, 2000, 5000 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:
mortality/morbidity: once daily from days 1 to 15, each animal is observed per Calvert SOP VET-14
clinical observations: clinical observations for any toxicological signs are recorded immediately after dosing, at 0.5, 1 and 4 hours post-dose on Day 1 and once daily thereafter through Day 15
body weight: Animals are weighed prior to dosing on Day 1 (fasted) and on Days 8 and 15
- Necropsy of survivors performed: yes
Statistics:
Parameters: body weights
Method: Raw data are summarized using descriptive statistics (mean and standard deviations). When necessary, additional analysis will be performed at the request of the Study Director. Additional analysis will be performed when necessary to augment the standard analysis.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
1000 mg/kg bw/d: 0/10
2000 mg/kg bw/d: 0/10
5000 mg/kg bw/d: 5/10 (1 male, 4 females)
Clinical signs:
other:
Body weight:
other body weight observations
Remarks:
No effects on body weight were observed.
Gross pathology:
No visible lesions were seen at 1000 and 2000 mg/kg bw/day. In the animals that were found dead on day 2 and 3 after exposure, following lesions were found: distended stomach, red to black fluid filled, dark lesions in stomach.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the mortalities observed after dosing 1000, 2000 or 5000 mg/kg bw/d (single dose, oral gavage), it is concluded that the LD50 is 5000 mg/kg bw/d.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

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:
other:
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:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): Amine C-8
- Substance type: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan or any other USDA approved vendor
- Age at study initiation: 8-24 weeks at start of dosing; records of dates of birth for animals used in this study will be retained in the Calvert archives
- Weight at study initiation: 175 to 300 g at the outset (Day 1) of the study
- Fasting period before study: no data
- Housing: Animals are housed (group housed by sex upon receipt, individually housed upon assignment to study) in compliance with the National Research Council "Guide for the Care and Use of Laboratory Animals". Calvert is a USDA registered and fully AAALAC accredited facility. The room in which the animals are kept is documented in the study records. No other species are kept in the same room.
- Diet (e.g. ad libitum): All animals have access to Harlan Teklad Rodent Diet (certified) or equivalent as per Calvert's SOP. The lot number and specifications of each lot used are archived at Calvert. No contaminants are known to be present in the certified diet at levels that would be expected to interfere with the results of this study. Analysis of the diet was limited to that performed by the manufacturer, records of which are maintained in the Calvert Archives
- Water (e.g. ad libitum): Tap water is available ad libitum, to each animal via an automatic watering device. The water is routinely analyzed for contaminants as per Calvert SOP's. No contaminants are known to be present in the water at levels that would be expected to interfere with the results of this study. Results of the water analysis is maintained in the Calvert archives.
- Acclimation period: Study animals will be acclimated to their housing for a minimum of 5 days prior to their first day of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: > or = 10%
- Type of wrap if used: the test article is applied on an intact skin site for each animal, covered with a gauze patch/dental dam, wrapped with an elastic bandage and secured with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): post-exposure, the site is unwrapped and wiped approximately to remove residual test article
- Time after start of exposure: no data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Constant volume or concentration used: yes/no
- For solids, paste formed: yes/no

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
Applied once and remains in contact with the skin for twenty-four ± 0.5 hours.
Doses:
2000 mg/kg
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:
Mortality/morbidity: once daily; each animal is observed for evidence of death or impending death as per Calvert SOP VET-14
Clinical observations: Clinical observations are recorded immediately after unwrap, and daily thereafter through Day 15. At the time of clinical observations, the dose site is evaluated for dermal irritation. If present, dermal irritation is scored and recorded. In addition to the observation of irritation, any leions and other toxic effects are fully described. Additional clipping of the fur may be conducted as needed to facilitate dermal observations.
Body weight: Animals are weighed prior to dosing on Day 1 and on Days 8 and 15 or upon death
- Necropsy of survivors performed: yes
Statistics:
Body weights will be summarized using descriptive statistics (mean and standard deviation). if the data allow, the LD50 with 95% confidence limits are calculated by the method of Litchfield and Wilcoxin. When the data permits, the LD50 is calculated for each sex.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities
Mortality:
no mortalities observed
Clinical signs:
other: On the second day after exposure: all animals showed abnormal gait. One animal showed dark fur around eyes. Abnormal gait continued untill day 3 in one animal. all animals appeared normal from day 4 till the end of the observation period.
Body weight:
other body weight observations
Remarks:
Normal body weight gain.
Gross pathology:
no visible lesions
Other findings:
Day 2 of observation period:
All females (5/5) and 1 male (1/5) showed well defined erythema and slight edema. Other males showed moderate to severe erythema and slight edema.

day 3 -7
All males showed moderate to severe erythema and moderate edema. All females showed moderate to severe erythema and edema.

day 8 -15
Effects disappeared in males (no or very slight erythema, no edema) while in females the effects increased. 4 out of 5 females showed necrosis and sloughing from day 10. One animal showed no erythema or edema.
Interpretation of results:
GHS criteria not met
Conclusions:
There were no mortalities observed after acute dermal exposure to 2000 mg/kg bw/d of the test substance in 10 rats. Shortly after exposure, local erythema and edema effects were observed in both males and females. The effects seemed to be reversible in males and 1 female. In the 4 other females, necrosis and slouching appeared.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute toxicity: oral


Calvert Laboratories, Inc. (2010) investigated acute oral toxicity (by gavage) of the test substance in male/female Sprague-Dawley rats. The study was performed equivalent to OECD Guideline 420 (fixed dose method, key study, K1). Following doses were applied: 1000, 2000, 5000 mg/kg bw. The LD50 was concluded to be 5000 mg/kg. For the dose levels of 1000 and 2000 mg/kg bw, no mortality was observed. In the 5000 mg/kg bw dose group, one male and four female animals died. No clinical signs were observed in the groups dosed 1000 or 2000 mg/kg bw. In the highest dose group, the following clinical signs were observed: decreased body tone (10/10 animals), brown discoloured fur around eyes (2/10), piloerection (2/10), abnormal gait and stance (3/10), discharge (clear) eye (1/10), decreased activity (1/10). Four animals were found dead on the second day after exposure. One animal was found dead on day 3. No effects on body weight were observed. No visible lesions were seen at 1000 and 2000 mg/kg bw. In the animals that were found dead on day 2 and day 3 after exposure, following lesions were found: distended stomach, red to black fluid filled, dark lesions in stomach.


 


Acute toxicity: inhalation


According to the REACH Regulation, in addition to the oral route, for substances other than gases, the information mentioned under sections 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. Based on the properties of the substance, the inhalation route of exposure is not considered to be relevant (column 2 adaptation, Annex VIII, section 8.5).


 


Acute toxicity: dermal


Calvert Laboratories Inc (2010) determined acute dermal toxicity in 5 male and 5 female rats following a GLP-compliant study performed equivalent to OECD guideline 402 (key study, Klimisch 1). Only one dose was tested (2000 mg/kg bw). No mortality was observed. Shortly after exposure, local erythema and edema effects were observed in both males and females. The effects seemed to be reversible in males and 1 female. In the 4 other females, necrosis and sloughing appeared.

Justification for classification or non-classification

Based on the available data and according to the criteria laid down in the CLP Regulation (EC) 1272/2008, the test substance should not be classified as acute toxic via the oral and dermal route.

No reliable acute inhalation studies are available for the test substance. Therefore, no conclusion can be made on the classification for acute inhalation toxicity for this substance.