Dimethyl(octyl)amine

Endpoint summary

Description of key information

Acute Oral Toxicity

According to the OECD Test Guideline 423 Acute Oral Toxicity Class Method, the LD50 of AD-1, when administered by gavage, orally to male albino rats, has an estimated acute oral LD50 of 382 mg/kg bw; orally to female albino rats, has an estimated acute oral LD50 of 162 mg/kg bw. Therefore 162 mg/kg bw is used for catergorising under GHS. According to EC 1272/2008 this would be classified as a category 3 toxicity hazard.

Acute Inhalation Toxicity

According to the OECD Test Guideline 436 Acute Inhalation Toxicity Class Method, the LC50 of AD-1 when administered by inhalation (aerosol), for female Sprague-Dawley rats is greater than 0.052 mg/L and less than 0.55 mg/L, the LC50 for male Sprague-Dawley rats is 0.59 mg/L. According to EC 1272/2008 this would be classified as a category 2 toxicity hazard for inhalation.

Acute Dermal Toxicty

The LD50 of AD-1 when administered dermally to male New Zealand White rabbits, has an estimated acute dermal LD50 of 4,000 mg/kg bw according to the method of Litchfield.

No symbol and risk phrases are required according to EEC labelling regulations. (EC 1272/2008)

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:

03 January 1996 - 13 September 1996

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)

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Specific details on test material used for the study:

The test material was prepared at appropriate concentrations in maize oil to permit administration at a constant volume-dosage of 10 ml/kg bodyweight
Dosages were calculated and expressed gravimetrically in terms of the material as received. Fresh formulations of the test material were prepared on the morning of administration and any surplus remaining after dosing was disposed of on the same day.
No analyses were undertaken to assess the stability, homogeneity or achieved concentrations of the test material in the vehicle.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were housed in stainless steel grid cages (RS Biotech, Northants, England). The grid floor ensured rapid removal of waste material to undertrays which were cleaned as necessary. Five animals of the same sex were accommodated in each cage, unless reduced by mortality. The cages were suspended in mobile stainless steel racks.
The animals were held in a limited-access facility. All rooms were kept at slight positive pressure relative to the outside and each had its own filtered air supply giving at least 10 complete air changes per hour without re-circulation. Target values for temperature and humidity were 21°C (range 19°-25°C) and 55% R.H (range 40%-70% R.H.), respectively. The achieved values were monitored daily. Electric time-switches regulated a lighting cycle of 12 hours of artificial light per day. An emergency generator was available to maintain the electricity supply in the event of a power failure. All personnel entering the building changed into clean protective clothing and wore an oversuit, gloves, plastic over-shoes and face mask to service animal holding areas. A commercially-available complete pelleted rodent diet (RMl(E) SQC, from Special Diets Services Limited, Witham, Essex, England) was fed ad libitum. The manufacturer supplied analytical data with each batch of diet which included concentrations of nutritional components, aflatoxins and selected
heavy metals, pesticides and micro-organisms. The diet contained no added antibiotic or other chemotherapeutic or prophylactic treatment. Samples of diet were taken for analysis at six-monthly intervals to detect potential contaminants by a laboratory independent of the supplier. Results of these analyses are retained in the archives.
Animals had free access to tap water taken from the public supply; in England the supply and quality of this water is governed by Department of the Environment regulations. Certificates of analysis were routinely received from the supplier (Essex and Suffolk Water pie). At approximately six-month
intervals water was routinely sampled for analysis, by a laboratory independent of the supplier, for selected chlorinated and organophosphorus pesticides, polychlorinated biphenyls and lead and cadmium contaminants; it was also examined for coliform bacteria. Results of these analyses are retained in the archives.

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

A preliminary study was carried out using two groups of one male and one female rat given an oral administration of AP-1 at dosages of 500 and 2000 mg/kg, at a constant volume-dosage of 10 ml/kg in maize oil.

Dose-volume was determined for each animal according to the fasted bodyweight on the morning of dosing. The dose was administered on Day 1 at a constant volume-dosage of 10 ml/kg bodyweight.
A flexible catheter was passed down the oesophagus allowing instillation of the dose into the lumen of the stomach. Each animal was returned to its cage and food hoppers were re-filled approximately three hours after dosing.

Doses:

the main study was carried out using a single group of five male and five female rats given an oral administration of AP-1 at the dosage of 50 mg/kg, at a constant volume dosage of 10 ml/kg in maize oil. Since no animal died a further group of five male and five female rats were treated at 500 mg/kg.

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

Three separate recordings of signs were made during the first hour after dosing and two further recordings during the remainder of Day I. From Day 2 onwards, the animals were inspected twice daily and recordings were made once daily. The circumstances of any death were recorded. Any animal showing severe or enduring signs of pain or distress was humanely killed. The bodyweight of each animal was recorded on the day before dosing and on Days I, 8 and 15. The test was terminated on the morning of Day 15.

Preliminary study:

A preliminary study was carried out using two groups of one male and one female rat given an oral administration of AD-1 at dosages of 500 and 2000 mg/kg, at a constant volume-dosage of 10 ml/kg in maize oil.

Key result

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

ca. 162 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Slope - 80 degrees

Key result

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

ca. 382 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Slope - 72 degrees

Key result

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

ca. 342 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Slope - 73°

Mortality:

Four male and five female animals treated at 500 mg/kg died on the day of dosing. There was no death amongst the animals treated at 50 mg/kg.

Clinical signs:

other: Ante mortem signs were restricted to prone posture in one female animal. The surviving animal treated at 500 mg/kg showed underactivity, staggering gait, hunched posture and piloerection; it was overtly normal after the first over night period. There was

Gross pathology:

Necropsy of the decedents revealed areas of fur staining and cases of distension of the small intestine by a yellow viscous fluid. There was no macroscopic abnormality detected amongst the surviving animals.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The test article, when administered by gavage, oral to male albino rats, has an estimated acute oral LD50 of 382 mg/kg bw with a slope of 72°.
The test article, when administered by gavage, oral to female albino rats, has an estimated acute oral LD50 of 162 mg/kg bw with a slope of 80°.
162 mg/kg bw is used for catergorising under GHS.

Executive summary:

The acute oral toxicity of AD-1 was investigated in two groups of five male and five female CD rats. The animals were starved overnight prior to dosing. The test material was administered at dosages of 50 and 500 mg/kg, at a constant volume-dosage of 10 ml/kg in maize oil. Mortality and signs of reaction to treatment were recorded during a subsequent 14-day observation period; the surviving animals were killed on the following day. All animals were subjected to necropsy.

The mortality distribution was as 4/5 males and 5/5 at 500 mg/kg bw. No mortality at 50 mg/kg bw. The deaths occurred on on the day of dosing.

Ante mortem signs comprised prone position. Signs of reaction in the surviving animal treated at 500 mg/kg comprised underactivity, staggering gait, hunched posture and piloerection. There was no sign of reaction to treatment amongst the animals treated at 50 mg/kg.

All surviving animals achieved anticipated bodyweight gains.

Necropsy findings for the decedents were unremarkable. There was no macroscopic abnormality evident amongst animals treated at 50 mg/kg.

Under the conditions of this study the acute oral median lethal dosage (LD50), of the test material was approximately 162 mg/kg in female animals.

Accordingly, AD-1 was assigned to Catergory 3.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

162 mg/kg bw

Quality of whole database:

Database considered realiable. Justification - data is based on a GLP guideline study.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-01-11 to 2016-06-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Housing: The animals were singly housed in suspended stainless steel caging, which conforms to the size recommendations in the most recent
Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Enrichment (e.g., toy) was placed in each cage. Litter paper was
placed beneath the cage and was changed at least three times per week.
Animal Room Temperature and Relative Humidity Ranges: 20-23ºC and 41-58%, respectively.
Animal Room Air Changes/Hour: 12. Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 6 or 14 days
Food: Envigo Teklad Global 16% Protein Rodent Diet® #2016. The diet was available ad libitum, except during the exposure.
Water: Filtered tap water was supplied ad libitum, except during the exposure.
Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with
the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Product Safety Labs.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

For each exposure, the exposure chamber, air supply, and equipment used to measure particle size distribution, airflow, and chamber concentration were the same as used during the respective pre-test trials and are described generally below.
Nose-Only Exposure Chamber: A nose-only inhalation chamber was used for exposure. Animals were individually housed in polycarbonate holding
tubes which seal to the chamber with an “O” ring during exposure. The base unit terminates the chamber with a 0.5-inch diameter tube for
discharged air.
Air Supply: Filtered generator air was supplied to the spray atomization nozzle by an air compressor, and measured with a Mass Flow Controller. Additional filtered mixing air from the same air compressor, measured with a Mass Flow Controller, was introduced into the chamber to help uniformly distribute the test atmosphere by creating a vortex at the chamber inlet. Chamber airflow was monitored throughout the exposure period and recorded periodically. The exposure was conducted under slight negative pressure.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

>= 4 h

Remarks on duration:

The animals were exposed to the targeted chamber concentration for at least 4 hours. The exposure period was extended beyond 4 hours to allow the chamber to reach equilibrium.

Concentrations:

Gravimetric samples were withdrawn at 6 intervals from the breathing zone of the animals. Samples were collected using 37 mm glass fiber filters
(Whatman™ GF/B) in a filter holder attached by ¼ inch Tygon® tubing to a vacuum pump. Filter papers were weighed before and after collection to
determine the mass collected. This value was divided by the total volume of air sampled to determine the chamber concentration. Sample airflows
were measured using a Mass Flow Controller.

No. of animals per sex per dose:

Number of Animals: 18
Sex: 9 Males and 9 Females. Females assigned to test were nulliparous and non-pregnant.
Number of Animals/Exposure Level: 3 Males and 3 Females

Control animals:

no

Details on study design:

Preparation of Test Substance
The test substance was aerosolized as received and kept on a magnetic stirrer during aerosolization, with the exception of the trials performed for the third level.
Pre-Test Trials
Prior to initiation of the full inhalation study, pre-test trials were conducted to establish generation procedures to achieve, to the extent possible,
the desired chamber concentration and desired particle size distribution (mass median aerodynamic diameter between 1 and 4 µm). In these trials, the following adjustments were made in an attempt to achieve these objectives:
Air Pressure: varied
Compressed Generator Airflow: varied
Compressed Mixing Airflow: varied
Total Airflow: varied
Liquid Pump Setting: varied
Liquid Pump Type: varied
Tubing Size: constant
Atomization System: constant
Clean-Out Needle and Fluid Cap: constant
Air Cap: constant
Vacuum Pump: constant
Concentration Sampling Time: varied
The procedures and aerosolization equipment used in the full test were based on the results of pre-test trial numbers 3, 12, and 17. In each
instance, the conditions of generation were modified to achieve the targeted chamber concentration with a desirable particle size distribution.

Selection of Animals
On the day of and prior to exposure, the rats were examined for health and weighed. Six healthy, naive rats (three males and three females;
not previously tested) were selected for each exposure.

Inhalation Procedures
For each exposure, the exposure chamber, air supply, and equipment used to measure particle size distribution, airflow, and chamber concentration were the same as used during the respective pre-test trials and are described generally below.
Nose-Only Exposure Chamber: A nose-only inhalation chamber was used for exposure. Animals were individually housed in polycarbonate holding
tubes which seal to the chamber with an “O” ring during exposure. The base unit terminates the chamber with a 0.5-inch diameter tube for
discharged air.
Air Supply: Filtered generator air was supplied to the spray atomization nozzle by an air compressor, and measured with a Mass Flow Controller.
Additional filtered mixing air from the same air compressor, measured with a Mass Flow Controller, was introduced into the chamber to help
uniformly distribute the test atmosphere by creating a vortex at the chamber inlet. Chamber airflow was monitored throughout the exposure period and recorded periodically. The exposure was conducted under slight negative pressure.
Ambient Conditions: The temperature and relative humidity within the exposure chamber as well as the room were monitored continuously during
exposure, and were measured with a temperature-humidity monitor. Temperature and relative humidity values were recorded every 15 minutes for
the first hour of exposure and approximately every 15 or 30 minutes thereafter.
Atmosphere Generation: The test atmosphere was generated using a nebulizer. The test substance was metered to the atomization nozzle through
PharMed BPT tubing, using a peristaltic pump.
Chamber Concentration Measurements: Gravimetric samples were withdrawn at 6 intervals from the breathing zone of the animals. Samples were
collected using 37 mm glass fiber filters (Whatman™ GF/B) in a filter holder attached by ¼ inch Tygon® tubing to a vacuum pump. Filter papers were weighed before and after collection to determine the mass collected. This value was divided by the total volume of air sampled to determine the
chamber concentration. Sample airflows were measured using a Mass Flow Controller.
Particle Size Distribution: An eight-stage 1 ACFM Andersen Ambient Particle Sizing Sampler was used to assess the particle size distribution of the
test atmosphere. Samples were withdrawn from the breathing zone of the animals at two intervals. The filter paper collection stages were weighed
before and after sampling to determine the mass collected upon each stage. The mass median aerodynamic diameter (MMAD) and geometric
standard deviation (GSD) were calculated using two-cycle logarithmic probit axes.
Exposure Period: The animals were exposed to the targeted chamber concentration for at least 4 hours. The exposure period was extended beyond 4 hours to allow the chamber to reach equilibrium. At the end of the exposure period, the generation was terminated and the chamber was operated
for at least 15 minutes further with clean air to allow the test atmosphere to fully dissipate. At the end of this period the animals were removed from
the exposure tubes. Prior to being returned to their cages, excess test substance was removed from the fur of each animal by rinsing with tap water and wiping with clean paper towels.

Body Weights
Individual body weights of the animals were recorded prior to test substance exposure (initial) and again on Days 1, 3, 7, and 14 (terminal) or after
death.

Cage-Side Observations
All animals were observed for mortality during the exposure period. The animals were examined for signs of gross toxicity, and behavioral changes upon removal from the exposure tube and at least once daily thereafter for 14 days or until death occurred. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior
pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Necropsy
Surviving rats were euthanized via CO2 inhalation on Day 14. Gross necropsies were performed on all decedents and euthanized animals. Tissues
and organs of the thoracic and abdominal cavities were examined.

Statistics:

Statistical analysis was limited to the calculation of the mean and standard deviation.

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

0.59 mg/L air

Based on:

test mat.

95% CL:

> 0.39 - < 0.9

Exp. duration:

4 h

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

>= 0.052 - <= 0.55 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

0.052 mg/L
All animals survived exposure to the test atmosphere.

0.55 mg/L
One male and three females died within one hour of exposure to the test atmosphere.

1.12 mg/L
All animals died following chamber removal.

Clinical signs:

other: 0.052 mg/L Following exposure, all rats exhibited irregular respiration. In addition, two females were noted as having ano-genital staining, tremors, and/or ataxia. However, all animals recovered from these symptoms by Day 3 and appeared active and h

Body weight:

0.052 mg/L
All animals gained body weight during the study.

0.55 mg/L
The survuving animals gained body weight during the study.

Gross pathology:

0.052 mg/L
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

0.55 mg/L
Gross necropsy of the decedents revealed discoloration of the lungs and liver and/or distention of the stomach. No gross abnormalities were
noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

1.12 mg/L
Gross necropsy of the decedents revealed discoloration of the lungs, liver, stomach, and/or intestines and/or distention of the stomach.

0.052 mg/L

The chamber and nominal chamber concentrations were 0.052 mg/L and 1.54 mg/L, respectively. The average mass median aerodynamic diameter was estimated to be 1.76 µm based on graphic analysis of the particle size distribution as measured with a 1 ACFM Andersen Ambient Particle Sizing Sampler with an average geometric standard deviation of 2.32.
All animals survived exposure to the test atmosphere and gained body weight during the study. Following exposure, all rats exhibited irregular respiration. In addition, two females were noted as having ano-genital staining, tremors, and/or ataxia. However, all animals recovered from these symptoms by Day 3 and appeared active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

0.55 mg/L

The chamber and nominal chamber concentrations were 0.55 mg/L and 6.48 mg/L, respectively. The average mass median aerodynamic diameter was estimated to be 1.70 µm based on graphic analysis of the particle size distribution as measured with a 1 ACFM Andersen Ambient Particle Sizing Sampler with an average geometric standard deviation of 2.17. One male and three females died within one hour of exposure to the test atmosphere. Prior to death, one female was hypoactive and exhibited irregular respiration and prone posture. There were no adverse clinical effects observed for the remaining one male and two females prior to death. Following exposure, the two surviving males exhibited abnormal respiration, ano-genital staining, tremors, and/or were hypoactive. However, the two surviving animals recovered by Day 4 and appeared active and healthy for the remainder of the 14-day observation period. Gross necropsy of the decedents revealed discoloration of the lungs and liver and/or distention of the stomach. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

1.12 mg/L

The chamber and nominal chamber concentrations were 1.12 mg/L and 9.10 mg/L, respectively. The average mass median aerodynamic diameter was estimated to be 2.28 µm based on graphic analysis of the particle size distribution as measured with a 1 ACFM Andersen Ambient Particle Sizing Sampler with an average geometric standard deviation of 2.65.

All animals died following chamber removal. There were no adverse clinical effects observed for any of the animals prior to death. Gross necropsy of the decedents revealed discoloration of the lungs, liver, stomach, and/or intestines and/or distention of the stomach.

Interpretation of results:

Toxicity Category II

Remarks:

Migrated information fatal if inhaled Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute inhalation defined LC50 of the test substance calculated by Probit Analysis was 0.59 mg/L in males with 95% confidence limits of 0.39 mg/L (lower) and 0.9 mg/L (upper). The data does not permit calculation of the LC50 for females by Probit Analysis.
The LC50 for females is greater than 0.052 mg/L and less than 0.55 mg/L. Based on an LC100 of 0.55 mg/L and an LC50 range of 0.052 to
0.55 mg/L in females, AD-1 may be classified according to Regulation 1272/2008 as Acute Toxicity Category 2; H330 fatal if inhaled.

Executive summary:

An acute inhalation toxicity test was conducted with rats to determine the potential for AD-1 to produce toxicity from a single exposure via the inhalation (nose-only exposure) route. Under the conditions of this study, the acute inhalation defined LC₅₀of the test substance calculated by Probit Analysis was 0.59 mg/L in males with 95% confidence limits of 0.39 mg/L (lower) and 0.9 mg/L (upper). The data does not permit calculation of the LC₅₀for females by Probit Analysis.  The LC₅₀for females is greater than0.052mg/L and less than 0.55 mg/L. 

Based on an LC₁₀₀of 0.55 mg/L and an LC₅₀range of 0.052 to 0.55 mg/L in females,  AD1 may be classified according to Regulation 1272/2008 as Acute Toxicity Category 2; H330 fatal if inhaled.

After establishing the desired generation procedures during the pre-test trials,eighteenhealthy rats were selected for test and equally distributed into three exposure groups(3 males and 3 females per exposure). Exposure levels of1.0, 0.5 and 0.05 mg/L were selected for testing. Each group of animals was exposed to the test atmosphere for approximately 4 hours.Chamber concentration and particle size distributions of the test atmosphere were determined periodically during the exposure period. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days following exposure or until death occurred. Body weights were recorded prior to exposure (initial) and again on Days 1, 3, 7, and 14 (terminal) or after death. Necropsies were performed on all animals.

The incidence of mortality at each exposure level is summarized below:

Exposure Concentration	Mortality
(mg/L)	Males	Females	Total
1.12	3/3	3/3	6/6
0.55	1/3	3/3	4/6
0.05	0/3	0/3	0/6

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

52 mg/m³ air

Quality of whole database:

Database considered realiable. Justification - data is based on a GLP guideline study.

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:

04/01/1980-08/02/1980

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 402 (Acute Dermal Toxicity)

Version / remarks:

Study conducted before OECD 402 was in existence. The LD 50 was calculated according to the method of Litchfield
J.T. Jr. & F. Wilcoxon (J. Pharm. & Exp. Therap. 96:99, 1949), or Horn, H.J.
Biometrics 12:311, 1956.

Principles of method if other than guideline:

Study conducted before OECD 402 was in existence.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

ADMA C8
Clear liquid, specific gravity 0.76 g/L

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

New Zealand White rabbits, approximately 8 weeks old when received, were equilibrated for at least one week in this laboratory. Apparently healthy rabbits were selected for the test. The animals were identified by cage tags noting the test material, starting date, animal number and sex. In addition, odd numbered animals in each cage were identified with an indelible ear mark. The animals were housed 2/cage in suspended wire mesh cages (30 11 x 18" x 1811). Fresh Purina rabbit chow and water were freely available. The animal room reserved exclusively for rabbits on acute tests, was maintained at 20 - 21 0 C and was kept clean in accordance with the standards of AAALAC of which this laboratory is an approved member.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The test material was applied once dermally to the prepared site under gauze patches. The patches were secured with adhesive tape and the trunks were wrapped with impervious material.

Duration of exposure:

The test material was kept in contact with the skin for 24 hours, at which time the wrappings were removed. An estimate of the amount of material remaining was recorded.

Doses:

20,000 mg/kg - group 1
16,000 mg/kg - group 2
4,000 mg/kg - group 3
1,000 mg/kg - group 4

No. of animals per sex per dose:

2 male/ 2 female - group 1
4 female - group 2
4 male - group 3
4 male - group 4

Control animals:

no

Details on study design:

A limit test was performed in which group one of two male and two female rabbits received a single dermal administration of the test article at a dose of 20,000 mg/kg body weight. Following dosing, all 4 rats died within 90 minutes therefore 3 additional groups of four rabbits were dosed at log intervals in an attempt to determine the LD 50. Doses were selected in an attempt to achieve at least two "partial kills"and if possible a "zero kill" and/or a "100% kill".
Dermal reactions were scored at 24 hours by the Draize scoring system. The rabbits were observed daily for14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded
pretest and in the survivors at 14 days. If there were deaths duri ng the study, all animals in the high dose group were examined for gross pathol ogy. In the lower dose levels, only animals which died during the study were examined for gross pathology.

Statistics:

The LD 50, if possible, was calculated according to the method of Litchfield J.T. Jr. & F. Wilcoxon (J. Pharm. & Exp. Therap. 96:99, 1949), or Horn, H.J. Biometrics 12:311, 1956.

Key result

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

4 000 mg/kg bw

Based on:

test mat.

Mortality:

0/4, 2/4, 4/4 and 4/4 animals died using this test substance at dose levels of 1,000, 4,000, 16,000 and 20,000 mg/kg of body weight respectively.

Clinical signs:

other: Skin reactions were pronounced; erythema was generally severe while edema was mostly moderate. The most common toxic sign was lethargy.

Gross pathology:

Animals dying before Day 14 had respiratory, cardiac and skin abnormalities.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The test article, when administered by dermal to male New Zealand White rabbits, has an estimated acute dermal LD50 of 4,000 mg/kg bw

Executive summary:

The test article, N,N-dimethyloctan-1-amine, was administered once dermally to the prepared site under gauze patches of male/female New Zealand White rabbits at varying test item concentrations. has an estimated acute dermal LD50 of 4,000 mg/kg bw.

0/4, 2/4, 4/4 and 4/4 animals died using this test substance at dose levels of 1,000, 4,000, 16,000 and 20,000 mg/kg of body weight respectively.

Skin reactions were pronounced; erythema was generally severe while edema was mostly moderate. The most common toxic sign was lethargy. Several surviving animals lost considerable amounts of weight.

Animals dying before Day 14 had respiratory, cardiac and skin abnormalities. The estimated acute dermal LD50 was determined to be 4,000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

4 000 mg/kg bw

Justification for classification or non-classification

Acute Oral Toxicity

According to the OECD Test Guideline 423 Acute Oral Toxicity Class Method, the LD50 of AD-1, when administered orally by gavage to male albino rats, has an estimated acute oral LD50 of 382 mg/kg bw; orally to female albino rats, has an estimated acute oral LD50 of 162 mg/kg bw. Therefore 162 mg/kg bw is used for catergorising under GHS.

Acute Inhalation Toxicity

According to the OECD Test Guideline 436 Acute Inhalation Toxicity Class Method, the LD50 of AD-1 when administered by inhalation (aerosol), the LC50 for female Sprague-Dawley rats is greater than 0.052 mg/L and less than 0.55 mg/L, the LC for male Sprague-Dawley rats is 0.59 mg/L

Acute Dermal Toxicty

The LD50 of AD-1 when administered dermally to male New Zealand White rabbits, has an estimated acute dermal LD50 of 4,000 mg/kg bw according to the method of Litchfield.